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Chromosome 2 alternate explanation - apes gaining a set of chromosomes?

Chromosome 2 alternate explanation - apes gaining a set of chromosomes?



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I'm preparing for a debate (just between friends) on evolution (I'm in support), and one of the points I plan to bring up is the Chromosome 2 evidence. I'm now trying to predict their potential rebuttals. The common statement I've seen is that since the apes have 48 chromosomes and humans have 46, then there are two possibilities: either we "lost" a chromosome, which would be fatal, or there was fusion. This, I believe, was an actual prediction prior to the answer of Chromosome 2 being identified. But couldn't there have been a third possibility - that the apes gained a pair of chromosomes, perhaps thru splitting of some kind? This seems reasonable to me due to the other claim that we didn't evolve from apes but that we share a common ancestor, and so the ape lineage could have acquired the extra chromosome after the split. (Note I'm a total biology noob, so if this doesn't even make sense, then please tell me.) I understand that this isn't the way it turned out, that Chr 2 looks exactly as we would expect from fusion, but prior to this discovery, couldn't the apes gaining a chromosome have been a possible reason? TIA.


I guess part of the question is… what exactly are you bring up Chromosome 2 as evidence of, exactly? It's evidence of that chromosomal rearrangements are possible, but that isn't terribly helpful to you, so I'm not sure why you are bringing it up.

I think the fusion is a rebuttal to a claim that the disparate # of chromosome is a problem for the claims of common ancestry between humans and other apes, but if they don't mention it, I'm not sure why you would need to use that particular fact.

Have you consulted talkorigin's 29 evidences of macroevolution? Lots of good stuff there.

http://www.talkorigins.org/faqs/comdesc/


Reconstruction of ancient chromosomes offers insight into mammalian evolution

What if researchers could go back in time 105 million years and accurately sequence the chromosomes of the first placental mammal? What would it reveal about evolution and modern mammals, including humans?

In a study published this week in Proceedings of the National Academy of Sciences, researchers have gone back in time, at least virtually, computationally recreating the chromosomes of the first eutherian mammal, the long-extinct, shrewlike ancestor of all placental mammals.

"The revolution in DNA sequencing has provided us with enough chromosome-scale genome assemblies to permit the computational reconstruction of the eutherian ancestor, as well as other key ancestors along the lineage leading to modern humans," said Harris Lewin, a lead author of the study and a professor of evolution and ecology and Robert and Rosabel Osborne Endowed Chair at the University of California, Davis.

"We now understand the major steps of chromosomal evolution that led to the genome organization of more than half the existing orders of mammals. These studies will allow us to determine the role of chromosome rearrangements in the formation of new mammal species and how such rearrangements result in adaptive changes that are specific to the different mammalian lineages," said Lewin.

The findings also have broad implications for understanding how chromosomal rearrangements over millions of years may contribute to human diseases, such as cancer.

"By gaining a better understanding of the relationship between evolutionary breakpoints and cancer breakpoints, the essential molecular features of chromosomes that lead to their instability can be revealed," said Lewin. "Our studies can be extended to the early detection of cancer by identifying diagnostic chromosome rearrangements in humans and other animals, and possibly novel targets for personalized therapy."

Descrambling chromosomes

To recreate the chromosomes of these ancient relatives, the team began with the sequenced genomes of 19 existing placental mammals -- all eutherian descendants -- including human, goat, dog, orangutan, cattle, mouse and chimpanzee, among others.

The researchers then utilized a new algorithm they developed called DESCHRAMBLER. The algorithm computed ("descrambled") the most likely order and orientation of 2,404 chromosome fragments that were common among the 19 placental mammals' genomes.

"It is the largest and most comprehensive such analysis performed to date, and DESCHRAMBLER was shown to produce highly accurate reconstructions using data simulation and by benchmarking it against other reconstruction tools," said Jian Ma, the study's co-senior author and an associate professor of computational biology at Carnegie Mellon University in Pittsburgh.

In addition to the eutherian ancestor, reconstructions were made for the six other ancestral genomes on the human evolutionary tree: boreoeutherian, euarchontoglires, simian (primates), catarrhini (Old World monkeys), great apes and human-chimpanzee. The reconstructions give a detailed picture of the various chromosomal changes -- translocations, inversions, fissions and other complex rearrangements -- that have occurred over the 105 million years between the first mammal and Homo sapiens.

Rates of evolution vary

One discovery is that the first eutherian ancestor likely had 42 chromosomes, four less than humans. Researchers identified 162 chromosomal breakpoints -- locations where a chromosome broke open, allowing for rearrangements -- between the eutherian ancestor and the formation of humans as a species.

The rates of evolution of ancestral chromosomes differed greatly among the different mammal lineages. But some chromosomes remained extremely stable over time. For example, six of the reconstructed eutherian ancestral chromosomes showed no rearrangements for almost 100 million years until the appearance of the common ancestor of human and chimpanzee.

Orangutan chromosomes were found to be the slowest evolving of all primates and still retain eight chromosomes that have not changed much with respect to gene order orientation as compared with the eutherian ancestor. In contrast, the lineage leading to chimpanzees had the highest rate of chromosome rearrangements among primates.

"When chromosomes rearrange, new genes and regulatory elements may form that alter the regulation of expression of hundreds of genes, or more. At least some of these events may be responsible for the major phenotypic differences we observe between the mammal orders," said Denis Larkin, co-senior author of the study and a reader in comparative genomics at the Royal Veterinary College at the University of London.

The chromosomes of the oldest three ancestors (eutherian, boreoeutherian, and euarchontoglires) were each found to include more than 80 percent of the entire length of the human genome, the most detailed reconstructions reported to date. The reconstructed chromosomes of the most recent common ancestor of simians, catarrhini, great apes, and humans and chimpanzees included more than 90 percent of human genome sequence, providing a structural framework for understanding primate evolution.


The 44 Chromosome Man

Many people have trouble believing that chromosome number can change and stay changed in a species. Their first thought is often of Down syndrome or the other problems that usually come with missing or extra chromosomes. It can be hard to imagine how a living thing could end up with a new chromosome number without these problems.

And yet it happens all the time in creatures as varied as yeast, corn, butterflies, voles and even mice. And now it has been seen in people.

In a recent article, a doctor in China has identified a man who has 44 chromosomes instead of the usual 46. Except for his different number of chromosomes, this man is perfectly normal in every measurable way.

His chromosomes are arranged in a stable way that could be passed on if he met a nice girl who had 44 chromosomes too. And this would certainly be possible in the future given his family history.

But why doesn't he have any problems? A loss of one let alone two chromosomes is almost always fatal because so many essential genes are lost.

In this case, he has fewer chromosomes but is actually missing very few genes. Instead, he has two chromosomes stuck to two other chromosomes. More specifically, both his chromosome 14's are stuck to his chromosome 15's.

So he has almost all the same genes as any other person. He just has them packaged a bit differently.

This is an important finding because it tells us about a key genetic event in human prehistory. All the evidence points to humans, like their relatives the chimpanzees, having 48 chromosomes a million or so years ago. Nowadays most humans have 46.

What happened to this 44 chromosome man shows one way that the first step in this sort of change might have happened in our past. Scientists could certainly predict something like this. But now there is proof that it can actually happen.

Note added in Proof: Here are some older papers that I missed that have very similar findings:

So how did this man end up with 44 chromosomes? It is a story of close relatives having children together. And a chromosomal rearrangement called a balanced translocation.

A balanced translocation is when one chromosome sticks to another. Because no genes are lost in this process, it usually doesn't have any effect. Until these folks try to have kids that is.

Usually around 2/3 of pregnancies involving one person with a balanced translocation will end in miscarriage. This has to do with how chromosomes separate when eggs and sperm are made. This process is called meiosis.

Remember, humans (and most other living things) have two copies of each chromosome. So they have two copies of chromosome 1, two copies of chromosome 2, etc. Only one chromosome from each pair gets put into any one sperm or egg. That way, when the sperm fertilizes the egg, the fetus has the right number of chromosomes.

This is where the problem starts for people with a balanced translocation. They have one unpaired chromosome and a pair with an extra chromosome. Here is what can happen in this situation:

The top row represents two potential parents. The parent on the right has a balanced translocation. There are two possible ways for the fused chromosome to line up.

In the figure, only two chromosomes are shown. Numbers 14 and 15 were chosen because these are the two that are fused in the 44 chromosome man.

The parent with the balanced translocation can make 4 different kinds of sperm or egg (the second row). As the figure shows, when the eggs and sperm combine, 1/2 of the time the fetus ends up with an extra or missing chromosome. Unless this chromosome is the X, Y or number 21, the usual result is miscarriage or being born with severe problems.

In this case it would almost certainly result in miscarriage. In fact, the 44 chromosome man's family has a long history of miscarriages and spontaneous abortions.

To get two of the same balanced translocations, both parents need to have the same balanced translocation. This is incredibly rare. Except when the parents are related.

In this case, both parents are first cousins and they share the same translocation. When these parents try to have kids, they run into the same kinds of problems that can happen with one balanced translocation. Except that the problems are doubled. This makes for the many possibilities outlined below:

This very complicated table shows the 36 possible outcomes when two parents with the same balanced translocation attempt to have a child.

In this representation, the father's possible sperm are shown on the top and the mother's eggs on the side. Each pregnancy has only an 8 in 36 chance for success. And 1 out of 36 would have two of the same balanced translocation (the circled possibility).

Theoretically the 44 chromosome man should have fewer problems having children than his parents did. As this figure shows, there are no unpaired chromosomes when he and a woman with 46 chromosomes have children. But all of their kids would have a balanced translocation:

So this is how he came to have 44 chromosomes. This might also be how humans started on the road to 46 chromosomes a million or so years ago.


The Fusion Motif Encodes a Functional Domain in the DDX11L2 Gene

As initially reported by Fan et al. (2002b), the putative 800 base fusion sequence is located somewhere inside a CHLR1 pseudogene within human chromosome region 2q13–2q14.1. The CHLR1 type category of genes in humans was originally annotated and characterized based on the DEAD family of DNA and RNA helicase genes, first discovered in yeast and found to be critical for proper chromosome transmission during mitosis (Gerring, Spencer, and Hieter 1990), and then eventually studied in humans (Abdelhaleem, Maltais, and Wain 2003 Cordin et al. 2006). The DEAD genetic acronym stands for the abbreviations of the amino acids associated with the key functional motif, the DEAD-box [asparagine (D), glutamic acid (E), alanine (A), asparagine (D)]. The DEAD-box helicases are thought to be enzymes that catalyze the separation and manipulation of nucleic acid polymers in an energy-dependent manner (Abdelhaleem, Maltais, and Wain 2003 Cordin et al. 2006).

Since the original complete sequencing of the fusion region on chromosome 2 (Fan et al. 2002a), the gene containing the fusion sequence has since been renamed from CHLR1 to DDX11L2 and found to be a member of the DDX11L family of at least 18 different RNA helicase genes (Costa et al. 2009). Oddly, while Costa et al. functionally and structurally characterized the DDX11L2 gene, they mentioned nothing of the fact that it contained the well-known chromosome 2 fusion sequence. Because the evolutionary model of gene origins is largely based on the idea of duplication from an original ancestral sequence, Costa et al. proposed that the variants of DDX11L genes in humans all evolved from ancestral sequences in apes. However, when a human DDX11L gene sequence was used as a cytogenetic probe for fluorescence in situ hybridization (FISH) in chimpanzee, it only hybridized to two places on chimp chromosomes 12 and 20 [image url: http://www.biomedcentral.com/1471-2164/10/250/figure/F3]. The same FISH experiment was also done in gorilla and showed four areas of gene synteny on chromosomes 3, 6, 7, and 20. In complete contradiction to evolutionary predictions, the human DDXL11L gene showed no synteny with chromosomes 2A or 2B in chimpanzee or gorilla (see image url above). This is highly significant because as described below, the fusion site appears to be a key functional motif contained within the DDX11L2 gene on chromosome 2. Furthermore, the fact that 18 copies of the DDX11L gene exists in humans verses only two copies in chimps and four in gorillas, is completely discordant with the inferred human-ape evolutionary phylogeny. Another evolutionary discordant fact about these genes is that their genomic locations are all different in each of the human and ape genomes.

Based on the most recent annotation of the human genome (GRCh37/hg19 http://genome.ucsc.edu), the

800 base purported fusion site is clearly contained within the first intron of the DDXL11L2 gene on human chromosome two as depicted in Fig. 2A, 2B. The DDXL11L2 gene is composed of three primary exons and is transcribed from the telomere to centromere direction on the minus strand (fig. 2A, 2B). Thus, the so-called fusion sequence is actually read (5' to 3') in the reverse complement as part of a functional gene, not the forward strand orientation as typically depicted by the so-called fusion signature sequence (Fairbanks 2010 Tomkins and Bergman 2011a). Additionally, the fusion site contains data tracks for transcription factor binding (fig. 2A, 2B) indicating that it contains a functional DNA binding domain. Specifically, the three transcription factors CTCF, cMyc, and Po12 have been shown to bind to the putative fusion region in chromatin immunoprecipitation DNA sequencing (ChIP-seq) studies.

Fig. 2. (A) UCSC genome browser data showing selected gene annotation and ENCODE-related tracks for the DDX11L2 gene locus with the 798 base fusion site positioned within the locus using BLAT. Analysis image accessed at genome.ucsc.edu on July 23, 2013. (B) Simplified graphic showing the fusion site inside the DDX11L2 gene for the full-length transcript. Arrow in first exon depicts direction of transcription. (Click image for larger view)

There are actually three regions of consensus transcription factor binding in the DDXL11L2 gene with the two strongest regions of binding occurring in the fusion site and also directly 5' and proximal to the first exon in the gene’s promoter region. These two main areas of transcription factor binding coincide with specific epigenetic markers associated with transcriptional activity (fig. 2A, 2B). Of particular importance is the extensive combinatorial presence of specific transcriptionally active histone marks associated with acetylation (H3K27ac, H3K9ac) and methylation-based (H3K4Me1, H3K4Me3) modifications identified across the fusion site and the genes promoter area. These transcriptionally active epigenetic chromatin marks coincide with the areas of transcription factor binding. Combined with the evidence for transcription factor binding domains, the combinatorial histone marks clearly demarcate these regions as transcriptionally active and key to the expression of the DDXL11L2 gene. Interestingly, the H3K27ac histone acetylation marks are also typically associated with active enhancer elements in long-range chromatin interactions associated with transcription (Creyghton et al. 2010 Zentner, Tesar, and Scacheri 2011) and, of course, associated with active gene promoters (Dunham et al. 2012 Harmston and Lenhard 2013).


Darwin's God

In the 2005 Kitzmiller v. Dover Area School District court case, federal judge John Jones was heavily influenced by the first expert witness, evolutionist Ken Miller. As Jones later recalled, he “was taken to school.” Unfortunately what Miller “taught” Jones was a series of scientific misrepresentations. Miller focused on two examples from molecular biology: a pseudogene and a fused chromosome. In both cases Miller gave Jones many facts but the lessons were carefully tailored to misrepresent both the science and evolutionary theory.

As I explained here, Miller’s pseudogene example included four key misrepresentations: that the pseudogene has no function and is broken, that the pseudogene DNA sequence has “errors” or “mistakes,” that there is no reason for broken genes aside from common descent, and that the evolutionary interpretation of such pseudogenes is objective science.

As was well known and documented when Miller and the ACLU lawyers devised Miller’s testimony, pseudogenes that had been investigated often exhibited functional roles, such as gene expression, gene regulation and generation of genetic diversity. Pseudogenes were found to be involved in gene conversion or recombination with functional genes. Pseudogenes sequences were found to be conserved with reduced nucleotide variability, excess synonymous over nonsynonymous nucleotide polymorphism, and other features that are expected in genes that have functional roles.

Any expert witness testifying on such a narrow topic would have been well aware of these well known results which were published by leading researchers in top tier scientific journals. And yet Miller gave no such perspective to the Dover court, and instead unequivocally represented his pseudogene example as non functional and broken. That was the evolutionary interpretation of pseudogenes, not what the scientific evidence was indicating.

And even if Miller’s selected pseudogene was truly broken, that would not mandate an evolutionary explanation as Miller unequivocally stated to the court. Miller told judge Jones that a pseudogene found in different cousin species, with common mutations, “must mean that these two organisms are descended with modification from another organism” and “leads us to just one conclusion,” which is evolution’s common descent. But this too was a lie, as any expert witness on this topic would know of the many instances of pseudogenes with mutations common to multiple species that do not fit the evolutionary pattern. In these cases even evolutionists must admit that common descent does not explain the mutations.

Perhaps most importantly, Miller’s pseudogene testimony misrepresented the evolutionary argument as objective science whereas Miller and the evolutionists, when not in federal court, make one religious argument after another. The religious foundation of evolution goes back to 18th century Enlightenment and before, and would automatically expel evolution from our public schools.

Miller’s pseudogene argument was just another example of a centuries-long history of religious mandates for evolution. Miller had been making such religious arguments for many years before Dover. He argued that life revealed features “that no engineer would stand for” so they must have evolved. That may be true, but such knowledge cannot come from objective science.

As Miller informed the Dover court, his pseudogene example was “just a mess.” That’s one of his favorite ways of making evolution’s religious argument. As he wrote more than 10 years before Kitzmiller:

It is a powerful argument, but it is not scientific. Miller routinely makes these religious arguments in his books and presentations, but they were carefully edited out for his testimony to the Dover court.

The ACLU lawyers and evolutionists argued that Intelligent Design is a religious theory because there was religious intent. They carefully traced this in early documents. But in evolutionary theory no such careful tracing is needed. The religious claims are boldly pronounced by evolutionists all through their literature. Darwin’s book was chocked full of religious claims, and today’s evolutionists are no different.

This hypocrisy of evolutionary thinking was equally evident in the second of the two examples Miller presented to the Dover court. In that example, Miller showed evidence that two of our chromosomes have been fused together and claimed it was powerful evidence for evolution: “the closer that we can get to looking at the details of the human genome, the more powerful the evidence has become.”

But from a scientific perspective, the fusion event occurred in, and spread through, the human population. There is no evolutionary relationship revealed. Even if evolution is true, this fusion event would give us no evidence for it. The fused chromosome did not arise from another species, it was not inherited from a human-chimp common ancestor, or any other purported common ancestor.

The reason why evolutionists find this argument to be so powerful is, once again, from a religious perspective. According to evolutionists, the evidence mandates evolution because it disproves creation and design. As evolutionist Barry Starr explains:

An alternative explanation is that the designers fused the two chromosomes together when they created humans. .

The difficulty with this idea is that there is no obvious advantage to having 46 chromosomes instead of 48. .

And even if there were , a designer who can easily put in the 60 million or so differences between humans and chimpanzees should be able to accomplish whatever results a chromosome fusion gives more elegantly than sticking two ape chromosomes together.

The power of the argument is not that evolution is confirmed, but rather than design is falsified. As Denis Alexander elaborates in his book Creation or Evolution, the fused chromosome “reveals our shared ancestry with the apes.” [211] Of course the chromosome reveals no such thing. It provides no more evidence for evolution than any other similarity. Starr, Alexander and the evolutionists may as well be discussing similarities we share with the apes in our bones or our biochemistry. But the evolutionists focus on cases such as the fused chromosome because these cases provide far more powerful religious evidence. As Alexander explains:

And likewise Miller, when not deceiving federal judges, makes this same argument about the very evidence he presented in the Dover court:

So all we have to do is to look at our own genome, look at our own DNA, and see, do we have a chromosome that fits these features?

We do. It's human chromosome number 2, and the evidence is unmistakable . We have two centromeres, we have telomere DNA near the center, and the genes even line up corresponding to primate chromosome numbers 12 and 13.

Is there any way that intelligent design or special creation could explain why we have a chromosome like this? The only way that I can think of is if you're willing to say that the intelligent designer rigged chromosome number 2 to fool us into thinking that we had evolved. The closer we look at our own DNA, the more detailed a glimpse we get of our own genome, the more powerful the evidence becomes for our common ancestry with other species.

In his testimony, Miller told the Dover court that:

And when out of court, he makes the same statement:

The difference is he carefully omits the religion when in court. Nor did Miller reveal to the court that evolution is in no way required to explain the chromosome fusion evidence.

Miller also omitted several other inconvenient truths. Judge Jones said he received the equivalent of a degree in the expert testimony, but that degree didn’t include the fact that, beyond speculation, evolution has no explanation for how chromosomes evolved in the first place. And Miller did not explain the great number (more than a thousand) genes unique to the human genome. Again, beyond speculation evolution does not explain the rapid appearance of these novel genes. Indeed, as one evolutionist admitted, the secret to evolving a human from a chimp is to make fast changes in just the right places:

Finally, Miller presented the chromosome fusion evidence as a “beautiful” confirmation of an evolutionary prediction. What he didn’t explain to the court is that science is full of theories known to be false which yet make all kinds of confirmed predictions.

The Kitzmiller trial was one long series of misrepresentations. Yes judge Jones was schooled, but he didn’t learn the truth.


Results

WZ Sex Determination Locus on LG3

Our analysis utilizes two Oreochromis genome assemblies—the chromosome-scale assembly of a LG1XX female O. niloticus ( Conte et al. 2019) and a new chromosome-scale assembly of a LG3ZZ male O. aureus ( Tao et al. 2020). In the O. niloticus assembly, 87.6 Mb of LG3 was assembled and anchored. In the O. aureus assembly, the size of the LG3 anchored assembly was 134.4 Mb. Much of the sequence that was unanchored in the O. niloticus assembly has now been anchored to LG3 in the O. aureus assembly ( supplementary file 1 , Supplementary Material online). These two new genome assemblies represent large advances in tilapia genomics, but they have not yet been used to study the origin of the giant sex chromosome.

The O. niloticus assembly was previously used to characterize several LG3WZ sex chromosomes. Using the new O. aureus assembly as the reference, we now recharacterize the sex determination region on LG3 in Pelmatolapia mariae ( Gammerdinger et al. 2019) and O. aureus ( Conte et al. 2017). FST analysis was used to characterize the genome-wide pattern of divergence between males and females of P. mariae and O. aureus which both show a large region of elevated divergence on LG3 ( supplementary file 2 , Supplementary Material online). The fine-scale boundaries of the sex-determining region for each species were determined by examining the number of WZ patterned SNPs in a 10-kb sliding window. The P. mariae WZ sex determination locus on LG3 starts at ∼25 Mb and extends to 134.4 Mb. The O. aureus LG3WZ sex determination locus starts at ∼30 Mb and extends to 134.4 Mb ( supplementary file 3 , Supplementary Material online). This recharacterization of the sex-determining region in these species using the new O. aureus ZZ reference has revealed many additional regions of the LG3 giant sex chromosome that were either unassembled and/or unanchored in the previous genome assemblies.

Conservation of Synteny

The Japanese medaka (Oryzias latipes) provides the most suitable outgroup for studying synteny of LG3 in the Oreochromini since medaka has a typical teleost karyotype of 24 chromosome pairs and is the most closely related species with high-quality chromosome-scale assemblies ( Ichikawa et al. 2017). Due to the fact that the LG3 giant sex chromosome is highly repetitive and contains many gene duplications ( Ferreira et al. 2010 Conte et al. 2017), comparison of one-to-one orthologs of five species was necessary to remove alignment artifacts (see Materials and Methods). Figure 2 provides a comparison of these five-way one-to-one orthologs of O. aureus LG3 to the corresponding medaka chromosome 18. LG3 is divided into three parts (LG3a, LG3a’, and LG3b) based on these patterns of synteny. LG3a consists of the region with conserved synteny comprising the first ∼42 Mb of O. aureus (99 one-to-one orthologs). LG3a’ consists of the middle ∼45 Mb (from ∼42 to ∼87 Mb) and contains only 12 one-to-one orthologs. LG3b consists of the last 47 Mb of O. aureus (from 87 to 134 Mb) and contains zero one-to-one orthologs to medaka. LG3b comprises 35% of the anchored LG3 giant sex chromosome and represents the region potentially originating from a B chromosome fusion. The one-to-one orthologs at the end of medaka chromosome 18 correspond to the final orthologs on LG3a’ in the middle of LG3. The assembly of O. niloticus LG3 (87 Mb) shows a similar pattern of synteny to medaka, although the boundary between LG3a’ and LG3b is not as well defined ( supplementary file 4 , Supplementary Material online). Several cichlid species outside of the tribe Oreochromini that do not have the LG3 giant chromosome show conserved synteny to medaka across this entire chromosome ( supplementary files 5–7 , Supplementary Material online). Additionally, it does not appear that LG3a’ and LG3b arose from a different autosome as they do not show detectable synteny with any other chromosomes.

Five-way, one-to-one ortholog alignments of Oreochromis aureus LG3 to medaka chromosome 18. Interstitial telomeric sequences (ITS) are labeled with black arrows.

Five-way, one-to-one ortholog alignments of Oreochromis aureus LG3 to medaka chromosome 18. Interstitial telomeric sequences (ITS) are labeled with black arrows.

Several previous cytogenetic studies have shown that O. niloticus LG3 contains two separate interstitial telomere repeat sequences (ITSs) ( Chew et al. 2002 Martins et al. 2004). These ITSs may be indicative of chromosome fusion events ( Azzalin et al. 2001 Bolzán 2017). Consistent with the cytogenetic studies, the O. aureus assembly also contains two interstitial telomere repeats arrays (TTAGGG)n that are present on LG3 at 116.9 Mb, 130.6 Mb. An additional telomere repeat array is located at the presumed actual telomeric end at 134 Mb (genome-wide list in supplementary file 8 , Supplementary Material online). The African cichlid-specific chromosome fusion events on LG7 and LG23, which occurred before the formation of the LG3 giant sex chromosome, have not left traces of ITSs detectable by either cytogenetic studies ( Chew et al. 2002 Martins et al. 2004) or the genome assemblies of O. aureus and O. niloticus ( supplementary file 8 , Supplementary Material online).

Patterns of Recombination

The pattern of recombination in O. niloticus was previously characterized using a high-density map ( Joshi et al. 2018 Conte et al. 2019). LG3a shows the typical sigmoidal pattern of recombination seen on other African cichlid chromosomes, in which recombination rate is low near the telomeres and high in the middle of the chromosome. LG3a’ has a lower level of recombination, and LG3b shows large regions of no recombination ( fig. 3). These patterns of recombination also coincide with the patterns of synteny ( fig. 2 and supplementary file 4 , Supplementary Material online). LG3a shows a high density of syntenic markers both between Oreochromis species, and in comparisons to medaka. LG3a’ shows a lower density of markers and smaller blocks of uninterrupted synteny in both the O. niloticus to medaka and O. aureus to medaka comparisons. LG3b shows relatively few syntenic markers between oreochromines, and no one-to-one orthologs with medaka.

Patterns of recombination in Oreochromis niloticus correspond to the organization of synteny between O. niloticus and O. aureus LG3. (a) Recombination of female (red) and male (blue) O. niloticus LG3 shown in cM (right) and linkage disequilibrium (r 2 > 0.97, left) in black. Adapted with permission from ( Conte et al. 2019). (b) Synteny of the 87-Mb anchored assembly of LG3 in O. niloticus, compared with the 134-Mb anchored assembly of LG3 in O. aureus, compared with the ancestral chromosome 18 in Oryzias latipes.

Patterns of recombination in Oreochromis niloticus correspond to the organization of synteny between O. niloticus and O. aureus LG3. (a) Recombination of female (red) and male (blue) O. niloticus LG3 shown in cM (right) and linkage disequilibrium (r 2 > 0.97, left) in black. Adapted with permission from ( Conte et al. 2019). (b) Synteny of the 87-Mb anchored assembly of LG3 in O. niloticus, compared with the 134-Mb anchored assembly of LG3 in O. aureus, compared with the ancestral chromosome 18 in Oryzias latipes.

Sequence Content of the Giant Chromosome

The sequence content of the oreochromine giant chromosome is unusual compared with 69 other teleost fish genome assemblies. Oreochromis niloticus has the highest number of immunoglobulin genes and more than double the number of immunoglobulin transcripts of any other teleost ( supplementary file 9 , Supplementary Material online). LG3a’ and LG3b account for 47.4% (100/211) of O. niloticus immunoglobulin genes ( supplementary file 10 , Supplementary Material online). Subtracting these, O. niloticus would have a slightly above average count (111 vs. the teleost average of 101). Overall, O. niloticus LG3 has a significantly higher number of immunoglobulin genes than expected genome wide (P = 8.22 × 10 −18 , Fisher’s exact test). The same is true for LG3a, LG3a’, and LG3b (P = 1.03 × 10 −6 , 2.36 × 10 −9 , and 0.0014, respectively, Fisher’s exact test). The Oreochromini also have the largest amount of total sequence of any teleost annotated as endogenous retrovirus (ERVs), of which LG3a’ and LG3b account for 13.8% (1.06 Mb of the total 7.67 Mb genome-wide). However, the Oreochromini do not have the highest number of ERV insertion events. This either suggests a fragmented and incomplete representation of these elements in teleost assemblies constructed from short-read sequence data ( Conte and Kocher 2015) and/or that oreochromine ERVs are more recent and intact, resulting in fewer annotated ERV copies than more highly decayed ERVs in other species. The Oreochromini also have the highest number of annotated long noncoding RNAs (lncRNAs) among teleosts. LG3a’ and LG3b account for 13.1% of these lncRNAs. LG3b has a high density of zinc-finger proteins relative to the rest of the genome, although the overall number of these zinc-finger proteins is similar to that in other teleosts. Additionally, LG3 contains a higher amount of satellite repeats than expected compared with the rest of the genome (P = 2.81 × 10 −12 , Fisher’s exact test and supplementary file 10 , Supplementary Material online). Finally, a gene ontology (GO) enrichment analysis of LG3b identified several significantly enriched terms, all related to immune regulation and immune response ( supplementary files 11 and 12 , Supplementary Material online).

The giant sex chromosome contains several large, highly repetitive, ampliconic gene arrays which are commonly found on both sex chromosomes and B chromosomes of other species ( Bellott et al. 2010). The extent of these ampliconic arrays can be seen on a chromosome scale by examining sequence similarity across LG3 ( fig. 4 and supplementary file 13 , Supplementary Material online). These ampliconic gene expansions are found most frequently in the nonrecombining regions of LG3b. However, some of these genes have also expanded throughout LG3 and are also seen in lower copy numbers in the freely recombining region on LG3a and lower recombining region of LG3a’. A table of genes that have undergone expansion on LG3 is provided in supplementary file 14 , Supplementary Material online.

(a) Dotplot of the Oreochromis aureus LG3 giant sex chromosome. (b) Locations of the ampliconic gene expansions which are sorted from top to bottom by number of copies on LG3. Supplementary file 14 , Supplementary Material online, provides details of each of these ampliconic genes.

(a) Dotplot of the Oreochromis aureus LG3 giant sex chromosome. (b) Locations of the ampliconic gene expansions which are sorted from top to bottom by number of copies on LG3. Supplementary file 14 , Supplementary Material online, provides details of each of these ampliconic genes.

Patterns of Transposable Elements on the Giant Chromosome

The LG3 giant chromosome has the highest density of repetitive elements across the genome ( Ferreira et al. 2010 Conte et al. 2019), which may be a signature of a fusion with a B chromosome. B chromosomes in cichlids have been characterized as having a much higher content of specific TE families relative to the A genome ( Coan and Martins 2018). One explanation for this might be that B chromosomes can act as a “safe-haven” for particular TEs ( McAllister and Werren 1997 Camacho et al. 2000 Werren 2011). Therefore, B chromosomes may be more likely to contain TE insertions diverged from copies on the A chromosomes. In the most extreme case, one might also expect selfish B chromosomes to contain private TE families not found in the A chromosomes. Oreochromis aureus LG3 contains three different unknown TE families that were not found on any other chromosome and which are present in at least 100 copies (see Materials and Methods), defined here as “completely private TE families.” Additionally, O. aureus LG3 contains six additional TE families that were present in at least 100 copies and were almost exclusively found on LG3 only (>98% of copies), defined here as “predominately private TE families” ( supplementary file 15 , Supplementary Material online). One of these families was annotated as a DNA/Dada element, whereas the remainder were unknown elements. These private TE families on LG3 were mostly found on LG3a’ and LG3b, whereas very few copies of these TE families were found on LG3a. The rest of the O. aureus genome contains only two chromosomes (LG4 and LG13) with completely private TE families (one each) and no other chromosomes containing a predominantly private TE family. The private TE results are similar for O. niloticus LG3 compared with the rest of the genome ( supplementary file 15 , Supplementary Material online).

The age of these private TEs is an important factor to consider as well. For example, if the private TEs were all very recent in age, then perhaps they arrived well after the potential B chromosome fusion event. On the other hand, if the private TEs were older in age, then this may be evidence that they evolved on the original B chromosome prior to a potential fusion. The genome-wide O. aureus repeat landscape ( supplementary file 16 , Supplementary Material online) is similar to the O. niloticus repeat landscape ( Conte et al. 2017, 2019). The completely private TE copies share a similar distribution of sequence divergence as the whole genome, with copies of all ages as is the case for the predominately private TE copies ( supplementary file 16 , Supplementary Material online). However, a two-sample Kolmogorov–Smirnov test indicates a significant difference between these two distributions (D = 0.198, P = 0.000). The difference in the cumulative frequency distributions is highest at a CpG adjusted Kimura substitution level of 10 ( supplementary file 17 , Supplementary Material online). This may indicate that these repeats derive from an older B chromosome.


Deletions

A deletion is simply the loss of a part of one chromosome arm. The process of deletion requires two chromosome breaks to cut out the intervening segment. The deleted fragment has no centromere consequently, it cannot be pulled to a spindle pole in cell division and will be lost. The effects of deletions depend on their size. A small deletion within a gene, called an intragenic deletion, inactivates the gene and has the same effect as other null mutations of that gene. If the homozygous null phenotype is viable (as, for example, in human albinism), then the homozygous deletion also will be viable. Intragenic deletions can be distinguished from single nucleotide changes because they are nonrevertible.

For most of this section, we shall be dealing with multigenic deletions, which have more severe consequences than do intragenic deletions. If by inbreeding such a deletion is made homozygous (that is, if both homologs have the same deletion), then the combination is always lethal. This fact suggests that most regions of the chromosomes are essential for normal viability and that complete elimination of any segment from the genome is deleterious. Even an individual organism heterozygous for a multigenic deletion—that is, having one normal homolog and one that carries the deletion—may not survive. Principally, this lethal outcome is due to disruption of normal gene balance. Another cause is the expression of deleterious recessive alleles uncovered by the deletion. (Most diploid organisms carry a load of such deleterious alleles.)

MESSAGE

The lethality of large heterozygous deletions can be explained by genome imbalance and expression of deleterious recessives.

Small deletions are sometimes viable in combination with a normal homolog. The deletion may be identified by cytogenetic analysis. If meiotic chromosomes are examined, the region of the deletion can be determined by the failure of the corresponding segment on the normal homolog to pair, resulting in a deletion loop (Figure 8-25a). In dipteran insects, deletion loops are also detected in the polytene chromosomes, in which the homologs are tightly paired and aligned (Figure 8-25b). A deletion can be assigned to a specific chromosome location by determining which chromosome shows the deletion loop, as well as the position of the loop along the chromosome.

Figure 8-25

Looped configurations in a Drosophila deletion heterozygote. In the meiotic pairing, the normal homolog forms a loop. The genes in this loop have no alleles with which to synapse. Because polytene chromosomes in Drosophila have specific banding patterns, (more. )

Another criterion for inferring the presence of a deletion is that deletion of a segment on one homolog sometimes unmasks recessive alleles present on the other homolog, leading to their unexpected expression. Consider, for example, the deletion shown in the following diagram:

In this case, none of the six recessive alleles is expected to be expressed but, if b and c are expressed, then a deletion that spans the b + and c + genes has probably occurred on the other homolog. Because, in such cases, it seems as if recessive alleles are showing dominance, the effect is called pseudodominance.

The pseudodominance effect can also be used in the opposite direction. A set of defined overlapping deletions is used to locate the map positions of new mutant alleles. This procedure is called deletion mapping. An example from the fruit fly Drosophila is shown in Figure 8-26. In this diagram, the recombination map is shown at the top, marked with distances in map units from the left end. The horizontal bars below the chromosome show the extent of the deletions identified at the left. The mutation prune (pn), for example, shows pseudodominance only with deletion 264�, which determines its location in the 2D-4 to 3A-2 region. However, fa shows pseudodominance with all but two deletions, so its position can be pinpointed to band 3C-7.

Figure 8-26

Locating genes to chromosomal regions by observing pseudodominance in Drosophila heterozygous for deletion and normal chromosomes. The red bars show the extent of the deleted segments in 13 deletions. All recessive alleles spanned by a deletion will be (more. )

MESSAGE

Deletions are recognized by deletion loops and pseudodominance.

Clinicians regularly find deletions in human chromosomes. In most cases, the deletions are relatively small, but they nevertheless have an adverse phenotypic effect, even though heterozygous. Deletions of specific human chromosome regions cause unique syndromes of phenotypic abnormalities. An example is the cri du chat syndrome, caused by a heterozygous deletion of the tip of the short arm of chromosome 5 (Figure 8-27). The specific bands deleted in cri du chat syndrome are 5p15.2 and 5p15.3, the two most distal bands identifiable on 5p. The most characteristic phenotype in the syndrome is the one that gives it its name, the distinctive catlike mewing cries made by infants with this deletion. Other phenotypic manifestations of the syndrome are microencephaly (abnormally small head) and a moonlike face. Like syndromes caused by other deletions, the cri du chat syndrome also includes mental retardation.

Figure 8-27

The cause of the cri du chat syndrome of abnormalities in humans is loss of the tip of the short arm of one of the homologs of chromosome 5.

Most human deletions, such as those that we have just considered, arise spontaneously in the germ line of a normal parent of an affected person thus no signs of the deletions are found in the somatic chromosomes of the parents. In rarer cases, deletion-bearing offspring can arise through adjacent segregation of a reciprocal translocation heterozygote or recombination within a pericentric inversion heterozygote. Cri du chat syndrome, for example, can result from a parent heterozygous for a translocation.

Animals and plants show differences regarding survival of deletions. A male animal that is heterozygous for a deletion and a normal chromosome produces functional sperm carrying one or the other of the two chromosomes in approximately equal numbers. In other words, sperm seem to function to some extent regardless of their genetic content. In diploid plants, on the other hand, the pollen produced by a deletion heterozygote is of two types: functional pollen carrying the normal chromosome, and nonfunctional (aborted) pollen carrying the deficient homolog. Thus, pollen cells seem to be sensitive to changes in amount of chromosomal material, and this sensitivity might act to weed out deletions. This effect is analogous to the sensitivity of pollen to whole-chromosome aneuploidy, described earlier in this chapter. Ovules in either diploid or polyploid plants, in contrast, are quite tolerant of deletions, presumably because of the nurturing effect of the surrounding maternal tissues.


EVENTS

There in the foaming welter of email constantly flooding my in-box was an actual, real, good, sincere question from someone who didn’t understand how chromosome numbers could change over time &mdash and he also asked with enough detail that I could actually see where his thinking was going awry. This is great! How could I not take time to answer?

How did life evolve from one (I suspect) chromosome to… 64 in horses, or whatever organism you want to pick. How is it possible for a sexually reproducing population of organisms to change chromosome numbers over time?

Firstly: there would have to be some benefit to the replication probability of the organisms which carry the chromosomes. I don’t see how this would work. How is having more chromosomes of any extra benefit to an organism’s replicative success? Yes, perhaps if those chromosomes were full of useful information… but the chances of that happening are non existent and fly in the face of ‘small adaptations over time’.

Secondly, the extra chromosomes need to come from somewhere. I’m not sure about this, but I believe chromosome number are not determined by genes, are they? There isn’t a set of genes which determines the number of chromosomes an organism has. So the number is fixed, determined by the sexually reproducing parents. Which leads me to believe that if the number does change, and by chance the organism is still alive and capable of sexual reproduction, that the number will start swinging back and forward, by 1 or 2, every generation, and never stabilising. The chances of this happening are also very very slim.

Let’s clear up a few irrelevant misconceptions first. Life probably started with no chromosomes &mdash early replicators would have been grab bags of metabolites, proteins, and RNA that would have simply sloppily split in two, with no real sorting. DNA and chromosomes evolved as accounting and archiving tools: they were a way to guarantee that each daughter cell in a division reliably received a copy of every gene. Also, most living things now just have one ‘chromosome’, a loop of DNA, and perhaps a small cloud of DNA fragments. So to keep this simple we’re going to ignore all that, and consider only us diploid eukaryotes, where the question of chromosome numbers becomes a real issue.

Normally, I’d be scribbling madly on a whiteboard, so we’ll have to make do with some scribbles on the computer screen. Here, for instance, is a typical cartoon chromosome. It’s a string of DNA, and scattered along it we have sequences for genes, that I’ve labeled “A”, “B”, “C”, “D”, and “E”. I’ve also drawn a circular blob in the middle: that’s important. It’s not a gene, it’s a structure called the centromere, which gets all wrapped up in proteins to form a kinetochore. It’s a sort of anchor point when the cell needs to move chromosomes around, as it does during cell division, it hitches motor proteins to the kinetochore and using drag lines called spindle fibers, tows it to a new destination.

I mentioned that this was a diploid organism &mdash that just means that every chromosome comes in pairs. This cell would have a similar chromosome to the one that has the ABCDE genes on it here I’ve draw it as containing the same genes, but in slightly different forms: abcde. This matters because during meiosis, when gametes (sperm and egg) are formed, the two chromosomes line up with one another and the cell machinery tows one chromosome to one daughter cell, and the other to the other daughter cell. It’s accounting it makes sure each daughter gets a copy of all of the genes, one A or one a, one B or one b, etc., for instance.

For now, put the fact that there are two copies of each chromosome at the back of your mind and don’t worry about it. Let’s think about a single chromosome and ask what can happen to it.

Here’s something fairly common. An error in copying the DNA can lead to the loss of a piece of DNA. This happens with a low frequency, but it does happen &mdash if we sequenced your DNA, we might well find a few bits missing here and there. We can get situations like this, where a whole gene gets lost.

Don’t panic! Remember that we have two copies of every chromosome, so while this one is missing the “D” gene, there’s that other chromosome floating around with a “d” gene. This is not necessarily bad for the individual, it just means he doesn’t have a spare any more.

Another kind of error that can happen with a low frequency is a duplication, where the machinery of the cell accidentally repeats itself when copying, and you get an extra copy of a piece of a chromosome, like so:

This person has two copies of D on this chromosome now (and remember that other chromosome, with it’s d gene &mdash he actually has 3 copies in total now). This is not usually harmful: it gives the individual a little extra redundancy, and that’s about it. It can change the total amount of the D gene product in the cell, and if it’s a gene for which precise dosage is important, it can have visible effects&hellipbut in most cases, this is a neutral change.

You may have noticed that nothing has changed the chromosome numbers yet. Here’s a situation that can lead to the formation of a new chromosome: what if there is a duplication of the centromere, rather than a gene?

Remember, I told you that the centromere/kinetochore is where the cell attaches lines and motors to haul the chromosome to the appropriate daughter cell. In this case, two lines are attached what if one tries to pull one centromere to the left, and the other tries to pull the other centromere to the right? Tug of war!

The end result is that the chromosome is broken into two chromosomes. I think this is a key concept that the questioner is missing: chromosome numbers really aren’t significant at all! You don’t need to add significant new information to create a new chromosome, and as I’ll show you in a moment, a reduction in chromosome numbers does not represent a loss of genetic information. Chromosome are disorganized filing cabinets, nothing more we can shuffle genes around between them willy-nilly, and the cell mostly doesn’t care. A fission event like the one described above basically does nothing but take one pile of genes and split them into two piles.

But there are some important effects. This may not be an entirely neutral situation. Let’s bring back that abcde chromosome, and pair it up with our two new chromosomes, AB and CDE.

The accounting is accurate. This cell has two copies of the A gene, an “A” and an “a”, just like normal, and the two new chromosomes can still pair up efficiently with the old chromosome in meiosis, just like before. This is a healthy, functioning, normal cell, except for one thing: if it goes through meiosis to make a sperm or egg, it’s going to make a larger number of errors. There are three centromeres there, to be split into two daughter cells! Never mind what the Intelligent Design creationists tell you &mdash the cell is really, really stupid, and it will more or less decide by eeny-meeny-miny-moe how to divvy up those chromosomes. If by chance the split is that one daughter gets AB + CDE, and the other gets abcde, both daughters have the full complement of genes and all is well. However, the split could also be that one daughter gets AB and nothing else, while the other gets CDE + abcde &hellip and that’s no good. One is missing a whole bunch of genes, and the other has an overdose of a bunch.

The net result is that although this individual is fine and healthy, a significant number of his or her gametes may carry serious chromosomal errors, which means they may have reduced fertility. They aren’t sterile, though some of their gametes will have the full complement of genes, and can similarly produce new healthy individuals who will probably have fertility problems. (Note: the significance of those fertility problems will vary from species to species. Organisms that rely on producing massive numbers of progeny so that a few survive to adulthood would be hit hard by a change that cuts fecundity species that rely on producing a few progeny that we raise carefully to adulthood, like us, not so much. So you have to have sex 20 times to successfully produce a child instead of 5 times that won’t usually be a handicap.)

So our two chromosome individual will have a reduced fertility as long as he or she is breeding with the normal one chromosome organisms, but those split chromosomes can continue to spread through the population. They are not certain to spread &mdash they’re more likely to eventually go extinct &mdash but by chance alone there can be continued propagation of the two chromosome variant. Which leads to another misconception in the question: something doesn’t have to provide a benefit to spread through a population! Chance alone can do it. We don’t have to argue for a benefit of chromosome fission at all in order for it to happen.

So we can have a population with a low frequency of scattered chromosomal variants, some carrying the rare two chromosome variant and others the more common one chromosome form. What if two individuals carrying the two chromosome variant breed? They can produce offspring that look like this:

How many centromeres are there? Four, not three. This is a situation the cell machinery can handle reliably, and this individual will consistently produce good gametes that accurately carry AB + CDE, nothing more, nothing less, and will have no reduction in fertility. Now we have a potentially interesting situation: individuals with the one chromosome situation have full fertility when breeding with other individuals with one chromosome individuals with two chromosomes have full fertility when breeding with other individuals with two chromosomes it’s when individuals with two different chromosome arrangements try to breed that fecundity is reduced. This is a situation where speciation is a possibility.

One last thing: what about reducing chromosome numbers? That’s easy, too. Here’s an organism with an AB chromosome, and a different chromosome with the genes MN on it. They can simply fuse in the region of the centromere.

This happens with a low frequency, too, and has been observed many times (hint: look up Robertsonian fusions on the web.) I think the key issue to understand here is that chromosome number changes are typically going to represent nothing but reorganizations of the genes &mdash the same genes are just being moved around to different filing cabinets. This has some consequences, of course &mdash you increase the chances of losing some important file folders in the process, and making it more difficult to sort out important information &mdash but it’s not as drastic as some seem to think, and chromosome numbers can change dramatically with no obvious effect on the phenotype of the organism. These really are “small adaptations over time”, or more accurately, “small changes over time”, since there is no necessary presumption that these are adaptive at all.

I’ve discussed fusion events and how they relate to evolution before, and there’s an interesting difference in context there, too. My prior article was a response to Casey Luskin, an ignorant creationist who used his misunderstanding of genetics to foolishly assert the existence of a major problem, and that’s where we have a conflict: ignorance is not a problem, but stupidly using your ignorance to push invalid ideas is. This question in my mailbox is also ignorant &mdash the fellow really doesn’t understand the basics of genetics &mdash but it’s self-recognized ignorance that, in a good way, prompts him to ask a sincere question.

If you want to dig a little deeper, there are many ways genetic information can be rearranged on chromosomes, and this has opened the doors to some interesting evolutionary research. I’ve described how we can map the reshuffling of chunks of genetic information over time, a process called synteny mapping, which allows us to reconstruct ancestral chromosomes. A fish might have 42 chromosomes, and we might have 46, but we can still trace how the ancestral arrangement was scrambled in many different ways to generate the modern arrangements.


Basics: How can chromosome numbers change?

There in the foaming welter of email constantly flooding my in-box was an actual, real, good, sincere question from someone who didn't understand how chromosome numbers could change over time — and he also asked with enough detail that I could actually see where his thinking was going awry. This is great! How could I not take time to answer?

How did life evolve from one (I suspect) chromosome to. 64 in horses, or whatever organism you want to pick. How is it possible for a sexually reproducing population of organisms to change chromosome numbers over time?

Firstly: there would have to be some benefit to the replication probability of the organisms which carry the chromosomes. I don't see how this would work. How is having more chromosomes of any extra benefit to an organism's replicative success? Yes, perhaps if those chromosomes were full of useful information. but the chances of that happening are non existent and fly in the face of 'small adaptations over time'.

Secondly, the extra chromosomes need to come from somewhere. I'm not sure about this, but I believe chromosome number are not determined by genes, are they? There isn't a set of genes which determines the number of chromosomes an organism has. So the number is fixed, determined by the sexually reproducing parents. Which leads me to believe that if the number does change, and by chance the organism is still alive and capable of sexual reproduction, that the number will start swinging back and forward, by 1 or 2, every generation, and never stabilising. The chances of this happening are also very very slim.

Let's clear up a few irrelevant misconceptions first. Life probably started with no chromosomes — early replicators would have been grab bags of metabolites, proteins, and RNA that would have simply sloppily split in two, with no real sorting. DNA and chromosomes evolved as accounting and archiving tools: they were a way to guarantee that each daughter cell in a division reliably received a copy of every gene. Also, most living things now just have one 'chromosome', a loop of DNA, and perhaps a small cloud of DNA fragments. So to keep this simple we're going to ignore all that, and consider only us diploid eukaryotes, where the question of chromosome numbers becomes a real issue.

Normally, I'd be scribbling madly on a whiteboard, so we'll have to make do with some scribbles on the computer screen. Here, for instance, is a typical cartoon chromosome. It's a string of DNA, and scattered along it we have sequences for genes, that I've labeled "A", "B", "C", "D", and "E". I've also drawn a circular blob in the middle: that's important. It's not a gene, it's a structure called the centromere, which gets all wrapped up in proteins to form a kinetochore. It's a sort of anchor point when the cell needs to move chromosomes around, as it does during cell division, it hitches motor proteins to the kinetochore and using drag lines called spindle fibers, tows it to a new destination.

I mentioned that this was a diploid organism — that just means that every chromosome comes in pairs. This cell would have a similar chromosome to the one that has the ABCDE genes on it here I've draw it as containing the same genes, but in slightly different forms: abcde. This matters because during meiosis, when gametes (sperm and egg) are formed, the two chromosomes line up with one another and the cell machinery tows one chromosome to one daughter cell, and the other to the other daughter cell. It's accounting it makes sure each daughter gets a copy of all of the genes, one A or one a, one B or one b, etc., for instance.

For now, put the fact that there are two copies of each chromosome at the back of your mind and don't worry about it. Let's think about a single chromosome and ask what can happen to it.

Here's something fairly common. An error in copying the DNA can lead to the loss of a piece of DNA. This happens with a low frequency, but it does happen — if we sequenced your DNA, we might well find a few bits missing here and there. We can get situations like this, where a whole gene gets lost.

Don't panic! Remember that we have two copies of every chromosome, so while this one is missing the "D" gene, there's that other chromosome floating around with a "d" gene. This is not necessarily bad for the individual, it just means he doesn't have a spare any more.

Another kind of error that can happen with a low frequency is a duplication, where the machinery of the cell accidentally repeats itself when copying, and you get an extra copy of a piece of a chromosome, like so:

This person has two copies of D on this chromosome now (and remember that other chromosome, with it's d gene — he actually has 3 copies in total now). This is not usually harmful: it gives the individual a little extra redundancy, and that's about it. It can change the total amount of the D gene product in the cell, and if it's a gene for which precise dosage is important, it can have visible effects…but in most cases, this is a neutral change.

You may have noticed that nothing has changed the chromosome numbers yet. Here's a situation that can lead to the formation of a new chromosome: what if there is a duplication of the centromere, rather than a gene?

Remember, I told you that the centromere/kinetochore is where the cell attaches lines and motors to haul the chromosome to the appropriate daughter cell. In this case, two lines are attached what if one tries to pull one centromere to the left, and the other tries to pull the other centromere to the right? Tug of war!

The end result is that the chromosome is broken into two chromosomes. I think this is a key concept that the questioner is missing: chromosome numbers really aren't significant at all! You don't need to add significant new information to create a new chromosome, and as I'll show you in a moment, a reduction in chromosome numbers does not represent a loss of genetic information. Chromosome are disorganized filing cabinets, nothing more we can shuffle genes around between them willy-nilly, and the cell mostly doesn't care. A fission event like the one described above basically does nothing but take one pile of genes and split them into two piles.

But there are some important effects. This may not be an entirely neutral situation. Let's bring back that abcde chromosome, and pair it up with our two new chromosomes, AB and CDE.

The accounting is accurate. This cell has two copies of the A gene, an "A" and an "a", just like normal, and the two new chromosomes can still pair up efficiently with the old chromosome in meiosis, just like before. This is a healthy, functioning, normal cell, except for one thing: if it goes through meiosis to make a sperm or egg, it's going to make a larger number of errors. There are three centromeres there, to be split into two daughter cells! Never mind what the Intelligent Design creationists tell you — the cell is really, really stupid, and it will more or less decide by eeny-meeny-miny-moe how to divvy up those chromosomes. If by chance the split is that one daughter gets AB + CDE, and the other gets abcde, both daughters have the full complement of genes and all is well. However, the split could also be that one daughter gets AB and nothing else, while the other gets CDE + abcde … and that's no good. One is missing a whole bunch of genes, and the other has an overdose of a bunch.

The net result is that although this individual is fine and healthy, a significant number of his or her gametes may carry serious chromosomal errors, which means they may have reduced fertility. They aren't sterile, though some of their gametes will have the full complement of genes, and can similarly produce new healthy individuals who will probably have fertility problems. (Note: the significance of those fertility problems will vary from species to species. Organisms that rely on producing massive numbers of progeny so that a few survive to adulthood would be hit hard by a change that cuts fecundity species that rely on producing a few progeny that we raise carefully to adulthood, like us, not so much. So you have to have sex 20 times to successfully produce a child instead of 5 times that won't usually be a handicap.)

So our two chromosome individual will have a reduced fertility as long as he or she is breeding with the normal one chromosome organisms, but those split chromosomes can continue to spread through the population. They are not certain to spread — they're more likely to eventually go extinct — but by chance alone there can be continued propagation of the two chromosome variant. Which leads to another misconception in the question: something doesn't have to provide a benefit to spread through a population! Chance alone can do it. We don't have to argue for a benefit of chromosome fission at all in order for it to happen.

So we can have a population with a low frequency of scattered chromosomal variants, some carrying the rare two chromosome variant and others the more common one chromosome form. What if two individuals carrying the two chromosome variant breed? They can produce offspring that look like this:

How many centromeres are there? Four, not three. This is a situation the cell machinery can handle reliably, and this individual will consistently produce good gametes that accurately carry AB + CDE, nothing more, nothing less, and will have no reduction in fertility. Now we have a potentially interesting situation: individuals with the one chromosome situation have full fertility when breeding with other individuals with one chromosome individuals with two chromosomes have full fertility when breeding with other individuals with two chromosomes it's when individuals with two different chromosome arrangements try to breed that fecundity is reduced. This is a situation where speciation is a possibility.

One last thing: what about reducing chromosome numbers? That's easy, too. Here's an organism with an AB chromosome, and a different chromosome with the genes MN on it. They can simply fuse in the region of the centromere.

This happens with a low frequency, too, and has been observed many times (hint: look up Robertsonian fusions on the web.) I think the key issue to understand here is that chromosome number changes are typically going to represent nothing but reorganizations of the genes — the same genes are just being moved around to different filing cabinets. This has some consequences, of course — you increase the chances of losing some important file folders in the process, and making it more difficult to sort out important information — but it's not as drastic as some seem to think, and chromosome numbers can change dramatically with no obvious effect on the phenotype of the organism. These really are "small adaptations over time", or more accurately, "small changes over time", since there is no necessary presumption that these are adaptive at all.

I've discussed fusion events and how they relate to evolution before, and there's an interesting difference in context there, too. My prior article was a response to Casey Luskin, an ignorant creationist who used his misunderstanding of genetics to foolishly assert the existence of a major problem, and that's where we have a conflict: ignorance is not a problem, but stupidly using your ignorance to push invalid ideas is. This question in my mailbox is also ignorant — the fellow really doesn't understand the basics of genetics — but it's self-recognized ignorance that, in a good way, prompts him to ask a sincere question.

If you want to dig a little deeper, there are many ways genetic information can be rearranged on chromosomes, and this has opened the doors to some interesting evolutionary research. I've described how we can map the reshuffling of chunks of genetic information over time, a process called synteny mapping, which allows us to reconstruct ancestral chromosomes. A fish might have 42 chromosomes, and we might have 46, but we can still trace how the ancestral arrangement was scrambled in many different ways to generate the modern arrangements.


Luskin's ludicrous genetics

I mentioned before that IDEA clubs insist that expertise is optional well, it's clear that that is definitely true. Casey Luskin, the IDEA club coordinator and president, has written an utterly awful article "rebutting" part of Ken Miller's testimony in the Dover trial. It is embarrassingly bad, a piece of dreck written by a lawyer that demonstrates that he knows nothing at all about genetics, evolution, biology, or basic logic. I'll explain a few of his misconceptions about genetics, errors in the reproductive consequences of individuals with Robertsonian fusions, and how he has completely misrepresented the significance of the ape:human chromosome comparisons.

In Miller's testimony, he talked about a basic fact of biology: most apes have 24 pairs chromosomes for a total of 48, while we have 23, for a total of 46. We are familiar with the fact that errors in chromosome number, called aneuploidies, within the human species are devastating and have dramatic effects the most familiar aneuploidy is Down syndrome, but there are others, which all lead to very short lifespans and extremely disabling phenotypes. Most aneuploidies are embryonically lethal and lead to spontaneous abortions. If evolution is valid, we should be able to see how that occurred historically, in a way that requires no mysterious interventions and only natural, observable mechanisms. Miller summarized it quite well.

Now, there's no possibility that that common ancestry which would have had 48 chromosomes because the other three species have 48, there's no possibility the chromosome could have just got lost or thrown away. Chromosome has so much genetic information on it that the loss of a whole chromosome would probably be fatal. So that's not a hypothesis.

Therefore, evolution makes a testable prediction, and that is, somewhere in the human genome we've got to be able to find a human chromosome that actually shows the point at which two of these common ancestors were pasted together. We ought to be able to find a piece of Scotch tape holding together two chromosomes so that our 24 pairs -- one of them was pasted together to form just 23. And if we can't find that, then the hypothesis of common ancestry is wrong and evolution is mistaken.

The answer is, of course, that the evolutionary prediction holds true: we do find the homologs of two genes fused together in our chromosome 2. We have the human and chimpanzee sequences, and we can see the same genes in our chromosome 2 that are found on two other chimpanzee chromosomes we can see the structure of two centromeres in our one chromosome, and also the relics of telomeres (normally at the ends of chromosomes) imbedded in the middle. It is an open-and-shut case.

Casey Luskin doesn't understand any of it. His response is to throw out a series of foolish speculations that have long since been discarded and that completely contradict all of the evidence.

Why couldn't it be the case that the common ancestor had 23 distinct chromosomes, and one chromosome underwent duplication in the line that led to apes? Or maybe the common ancestor had 20 distinct chromosomes and there have been 4 duplications events in the ape line, and 3 in the human line? or maybe the ancestor had 30 distinct chromosomes and there have been 6 fusion events for ape-line but 7 fusion events for the human-line.

Do you see my point? Simple chromosome-counting or comparisons of numbers of chromosomes does not lead common ancestry to make any hard predictions about how many chromosomes our alleged ape-human common ancestor had. So, under Miller's logic, there is no reason why a chromosomal fusion event is a necessary prediction of common ancestry for all upper primates.

That's pathetic. The reason evolutionists proposed a chromosomal fusion event is that all of the duplication events he proposes would have major phenotypic consequences (Down syndrome is caused by a duplication of one very small chromosome, for instance) and would represent a serious obstacle to evolution—Miller stated so very plainly. Some lineages are tolerant of that kind of massive genomic change, but ours is not. Multiple independent fusions are possible, but improbable we can see evidence of it in species that have diverged for a long time (mouse and human chromosomes are dramatically rearranged relative to one another, for instance), but apes haven't been separated as long. We have also had evidence for about 40 years that on a gross level, the structure of the chromosomes in all apes was very similar.

Luskin is tossing around these wild ideas in a very lawyerly tactic—he's trying to cast doubt on the best explanation by pretending there are a multitude of alternatives. Those alternatives are not reasonable, and he knows it: he even admits it.

So I am more than willing to acknowledge and affirm that Miller did provide some very good direct empirical evidence for a chromosomal fusion event which created human chromosome #2. But I'm more interested in two other questions: if we accept Miller's chromosomal fusion evidence as accurate, then (1) is his chromosome fusion story good evidence for Neo-Darwinian common ancestry between humans and apes? Or (2) does it perhaps pose great problems for a Neo-Darwinian account?

The answer to question (1) is "NO" and the answer to question (2) is "YES!"

Oh, dear. This is where Luskin goes off the rails, and abandons all reason.

(1) is a bogus framing of the issue. The fusion is not evidence of common ancestry it's the common genomic content of all ape chromosomes that is the evidence. The fusion accounts for a superficial difference in the appearance of the karyotype, but the underlying genetic sequence is what exposes the relatedness of humans and other apes. Luskin harps on this bizarre notion of his, that the occurrence of a fusion is the key to human evolution.

All Miller has done is documented direct empirical evidence of a chromosomal fusion event in humans. But evidence for a chromosomal fusion event is not evidence for when that event took place, nor is it evidence for the ancestry prior to that event.

Yes, that is correct. Miller wasn't claiming anything about when it occurred, or that the fusion says anything about prior ancestry: it's the sequence, stupid. But look here, here's Luskin's real agenda.

Given that we had a 48-chromosome ancestor, we don't know if our 48-chromosome ancestor was an ape or not. For all we know, our 48-chromosome ancestor was a part of a separately designed species, as fully human as anyone you meet on the street today. There is no good reason to think that going from a 46-chromosome individual to a 48-chromosome individual would make our species more ape-like.

Separate creation. We ain't descended from no monkeys. Miller's point is that chromosome number is not a good indicator of different ancestry, but Luskin wants to turn that around and claim any ol' ancestry is therefore equally valid…but it's not. It's the sequence, not the fusion, that tells us of our relatedness. And of course no one has proposed that a simple chromosome fusion or separation is responsible for the differences between us and other apes.

That humans are most closely related to apes and that we all had a common ancestor in the relatively recent past is not a point in contention by any reasonable scientist. This is the kind of false malarkey the IDists want to push in our schools—it's simply bad science to deny common ancestry.

What about Luskin's point (2), that the fused chromosome is a problem for the neo-Darwinian account? It's more nonsense (what else would you expect?).

Under Neo-Darwinism, genetic mutation events (including chromosomal aberrations) are generally assumed to be random and unguided. Miller's Cold-Fusion tale becomes more suspicious when one starts to ask harder questions like "how could a natural, unguided chromosomal fusion event get fixed into a population, much less how could it result in viable offspring?" Miller's account must overcome two potential obstacles:

(1) In most of our experience, individuals with the randomly-fused chromosome can be normal, but it is very likely that their offspring will ultimately have a genetic disease. A classic example of such is a cause of Down syndrome.

Not quite. What we see in humans is a classic instance of a Robertsonian translocation. These happen quite often—1 in 900 births bear a fusion of this kind—and they cause no immediate problems at all. The affected individual has a full and normal genetic complement it's just that two of their chromosomes are stuck together. It can cause reduced fertility, but is unlikely (except in some known, specific cases) to lead to offspring with a genetic disease.

Let me explain why. Assume we have a set of genes (a) found on one chromosome, and a set of genes (b) found on another. Everyone has two copies of each set, so in a normal diploid cell, we have (a) (a) (b) (b). In meiosis, the cellular mechanisms segregate the chromosomes in an orderly way, so each gamete gets one set (a) and one set (b), each gamete looks like this: (a) (b).

In an individual with a Robertsonian fusion, though, each diploid cell looks like this: (a) (b) (a:b). They have three chromosomes instead of four, even if they do have the proper doses of (a) and (b). Now when meiosis occurs, the cell has to sort 3 chromosomes into two cells, and there are multiple ways this can happen:

(a) (b) a normal gamete : normal
(a:b) a gamete carrying the fusion, but with the normal complement of genes: normal
(a) (a:b) a gamete with an extra (a)—lethal
(a) a gamete with an no (b)—lethal
(b) (a:b) a gamete with an extra (b)—lethal
(b) a gamete with a no (a)—lethal

As you can see, several of the combinations produce viable gametes, and this individual can have healthy children with no detectable problems, although half of them will carry the Robertsonian fusion. The other gametes have serious problems, and will typically lead to very early miscarriages, especially if they involve a large chromosome, like chromosome 2. They will have more problems conceiving, but their children will be normal.

If the fusion chromosome spreads through the population, something interesting will happen, and some people will have diploid cells like this: (a:b) (a:b). All of their gametes will be (a:b), and all will be normal. Fusions like this put up measurable but not at all insurmountable barriers to reproduction and can make it easier for carriers to reproduce with each other, so they can be mechanisms for reproductive isolation and speciation.

Again, Luskin doesn't understand this basic concept, and he compounds his error with quote mining and poor scholarship.

(2) One way around the problem in (1) is to find a mate that also had an identical chromosomal fusion event. But Valentine and Erwin imply that such events would be highly unlikely: "[T]he chance of two identical rare mutant individuals arising in sufficient propinquity to produce offspring seems too small to consider as a significant evolutionary event."

(Erwin, D..H., and Valentine, J.W. "'Hopeful monsters,' transposons, and the Metazoan radiation", Proc. Natl. Acad. Sci USA, 81:5482-5483, Sept 1984)

The problem in (1) is not a problem. As I just explained, you don't need a mate with an identical fusion event to successfully reproduce.

His choice of an article to back up his assertion is weird. The article is from 1984, for one thing why dig up a 22 year old article to support a basic point? For another, the article does not discuss the viability of hybrids with Robertsonian fusions at all. It is specifically about the possibility of large scale mutations that generate major morphological novelties.

The article is a short speculative work that suggests a way to get around the objection they mention, and that is the center of Luskin's argument—in other words, it's a paper that says how Luskin is wrong. (It also happens to be a proposal I don't find too likely: Erwin and Valentine suggest that one way the frequency of novel mutations could rapidly rise to overcome the problem is by site-specific horizontal transfer of transposable elements. Mmmm, maybe, but I'd want to see more evidence of such transformations associated with key innovations.)

Fortunately for the short attention span of creationist, their quote is from the second sentence of the paper. I can only assume they didn't bother to read any further. Does anyone else have this mental image of Discovery Institute "scholars" poring over science papers with almost no comprehension, but happily plucking out random sentences here and there that they can misuse? I suspect they have a compendium of such fragments that their fellows use, without the need of ever having to actually read any science.

In other words, Miller has to explain why a random chromosomal fusion event which, in our experience ultimately results in offspring with genetic diseases, didn’t result in a genetic disease and was thus advantageous enough to get fixed into the entire population of our ancestors. Given the lack of empirical evidence that random chromosomal fusion events are not disadvantageous, perhaps the presence of a chromosomal fusion event is not good evidence for a Neo-Darwinian history for humans.

No, no. Duplications in humans lead to genetic diseases. Miller was explaining that there is a normal genetic mechanism for fusions that represents an evolutionary pathway without the detriment of a major duplication/deletion that leads to our current chromosome arrangements.

The only guy proposing a path by way of duplications and their concomitant problems was Luskin.

Miller may have found good empirical evidence for a chromosomal fusion event. But all of our experience with mammalian genetics tells us that such a chromosomal aberration should have resulted in a non-viable mutant, or non-viable offspring. Thus, Neo-Darwinism has a hard time explaining why such a random fusion event was somehow advantageous.

Whoa, irony meter, calm down. Luskin telling us about "all of our experience with mammalian genetics"? He's wrong. He doesn't even have basic textbook knowledge of genetics. Our experience with mammalian genetics tells us that he is babbling out of his butt: fusions have no such problem yielding viable offspring.

If you bother to take a look at the list of articles maintained by the IDEA center, you'll see that the majority of them are by Luskin, and he's usually pontificating about similarly imaginary problems in evolutionary theory, problems that are actually with his own shameful lack of knowledge about the subject. This pathetic ignoramus is the primary source of information for the collegians they're trying to recruit into their IDEA clubs? I'd consider it a source of embarrassment to have an organization dedicated to such foolishness on my campus.


Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals.

Almost every cell in our body contains 23 pairs of chromosomes, for a total of 46 chromosomes. Half of the chromosomes come from our mother, and the other half come from our father. The first 22 pairs are called autosomes. The 23rd pair consists of the sex chromosomes, X and Y. Females usually have two X chromosomes, and males usually have one X and one Y chromosome in each cell. All of the information that the body needs to grow and develop comes from the chromosomes. Each chromosome contains thousands of genes, which make proteins that direct the body’s development, growth, and chemical reactions.

Many types of chromosomal abnormalities exist, but they can be categorized as either numerical or structural. Numerical abnormalities are whole chromosomes either missing from or extra to the normal pair. Structural abnormalities are when part of an individual chromosome is missing, extra, switched to another chromosome, or turned upside down.

Chromosomal abnormalities can occur as an accident when the egg or the sperm is formed or during the early developmental stages of the fetus. The age of the mother and certain environmental factors may play a role in the occurrence of genetic errors. Prenatal screening and testing can be performed to examine the chromosomes of the fetus and detect some, but not all, types of chromosomal abnormalities.

Chromosomal abnormalities can have many different effects, depending on the specific abnormality. For example, an extra copy of chromosome 21 causes Down syndrome (trisomy 21). Chromosomal abnormalities can also cause miscarriage, disease, or problems in growth or development.

The most common type of chromosomal abnormality is known as aneuploidy, an abnormal chromosome number due to an extra or missing chromosome.Most people with aneuploidy have trisomy (three copies of a chromosome) instead of monosomy (single copy of a chromosome). Down syndrome is probably the most well-known example of a chromosomal aneuploidy. Besides trisomy 21, the major chromosomal aneuploidies seen in live-born babies are: trisomy 18 trisomy 13 45, X (Turner syndrome) 47, XXY (Klinefelter syndrome) 47, XYY and 47, XXX.

Structural chromosomal abnormalities result from breakage and incorrect rejoining of chromosomal segments. A range of structural chromosomal abnormalities result in disease. Structural rearrangements are defined as balanced if the complete chromosomal set is still present, though rearranged, and unbalanced if information is additional or missing. Unbalanced rearrangements include deletions, duplications, or insertions of a chromosomal segment. Ring chromosomes can result when a chromosome undergoes two breaks and the broken ends fuse into a circular chromosome. An isochromosome can form when an arm of the chromosome is missing and the remaining arm duplicates.

Balanced rearrangements include inverted or translocated chromosomal regions. Since the full complement of DNA material is still present, balanced chromosomal rearrangements may go undetected because they may not result in disease. A disease can arise as a result of a balanced rearrangement if the breaks in the chromosomes occur in a gene, resulting in an absent or nonfunctional protein, or if the fusion of chromosomal segments results in a hybrid of two genes, producing a new protein product whose function is damaging to the cell.

All Genetic Alliance content, except where otherwise noted, is licensed under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Watch the video: Strukturne hromozomske mutacije (August 2022).