Saturday, 22 November 2014

The Genomic Evidence for Common Descent: 1. Synteny and the chromosome 2 fusion event

The evidence for common descent just from comparative genomics alone is overwhelming. As more than one person has said, even if every single fossil vanished, we would still be able to demonstrate the fact of common descent from the record in the genomes of all living creatures. We can see this from:
  • The shared order of genes in living creatures
  • Similar genes in related creatures
  • The presence of identical genetic 'glitches' (pseudogenes, retrotransposons, endogenous retroviral elements, telomeric DNA, 'scars' of DNA repair, and mitochondrial DNA elements in nuclear DNA) in the same places in genomes of related species
This is precisely what we would expect if common descent was true. Conversely, there is simply no credible special creationist explanation, other than to say God has deliberately created life both with genetic errors (our failure to synthesise vitamin C is a fatal inborn error of metabolism as without vitamin C we die from scurvy) and placed exactly the right pattern of mutations, broken genes, remnants of ancient viral infection and fragments of mobile DNA as to simulate common descent. Apart from being an ad hoc explanation writ large, it also makes God out to be a deceiver, and as one person once put it God is not the author of a lie, not even a white one.


If one uses the metaphor of a library to describe the genome, then one could describe a chromosome as a long library shelf with each book on it representing a gene. When we compare life forms, we find an interesting thing: the more closely related species are, the more similar will be their order of genes. The term for this conservation of order is synteny, which as delopmental biologist Paul Myers notes is "the conservation of blocks of order within two sets of chromosomes that are being compared with each other." [1]

This phenomenon is of great use as it provides us with a means of reconstructing evolutionary history. Biologists Darrel Falk and Dennis Venema (both evangelical Christian) shows how understanding synteny allows us to unravel the evolutionary history of fruit flies:
Drosophila species have about 14,000 genes lined up “single file” along their chromosomes. Below is the representation of a tiny portion of a chromosome of Drosophila melanogaster. Each number corresponds to a different gene. Notice that genes, 2799, 2807, 2808, and 2828 (and others which are noted only by the ellipsis) make up a syntenic block, Similarly the genes on the right (along with others not shown) also make up a syntenic block.
Now, here are these genes in a sister species, Drosophila ananassae:
Compare the gene order of the two sister species. Can you figure out what has happened to disrupt the block of genes 2799, 2807, 2808, and 2828—genes which exist side by side in melanogaster
Here’s a little hint:
Got it? There were two simultaneous breaks at some point in history so that 2799, 2807, 2808, and 2828 are no longer syntenic. Nor is the other block syntenic any more. Notice that in ananassae the same genes are present but they are in an inverted order. Two syntenic blocks have been broken up. We know exactly how it happened. 
Now imagine analyzing this for all twelve species and—in each case—examining all 14,000 (or so) genes. The position of every chromosome break in the time since the 12 species had a common ancestor has been mapped out. 40 million years of history has been all laid out showing the set of disruptions of the single file order in which the genes are stored. We even know about how often those disruptions occur in a lineage: breaks, like the two described above, take place about once every 200,000 years. This rate has been fairly constant in the approximately 40 million year history of these twelve lineages. Species that diverged only recently (judged by an independent mechanism) have only a small number of breaks and a large amount of synteny, On the other hand, species which diverged longer ago (again, as judged by an independent mechanism), have a much larger number of breaks and a smaller degree of synteny. [2]
It is easy to see how one can reconstruct an evolutionary family history by comparing the genomes of related creatures, looking for syntenic patterns, and unravelling the order in which such shuffling of gene blocks took place. Conversely, special creation has to explain:
  1. Why closely related species have such reversal of gene orders that look for all the world like translocations if they were specially created
  2. Why they need their genes in that order
In the absence of any compelling answers to those questions which explain the data far more convincingly than the evolutionary model, there is no reason to doubt the long-standing evolutionary explanation for this phenomenon.

Chromosome 2 Fusion

Humans have 23 pairs of chromosomes, while the great apes have 24 pairs of chromosomes. Common descent would predict that one of the human chromosomes would owe its formation to a fusion event. This is indeed the case. Human chromosome 2 owes its origin to the fusion of two chromosomes homologous to ape chromosome. Special creationists are unable to deny this fact, and resort to quote mining technical papers on cell biology in a desperate attempt to cloud the issue.

Our understanding of the origin of chromosome 2 in a fusion event is not new. We've known about the close similarity between human and ape chromosomes as long as thirty years ago, with the researchers behind the seminal paper in Science in which this data was published noting:
"The telomeric fusion of chromosomes 2p and 2q accounts for the reduction of the 24 pairs of chromosomes of the great apes to 23 in modern man. [3]" 
As one can see below, the similarities are striking:


Over the following 30 years, further work has pinpointed the exact location in human chromosome 2 where the fusion event occurred. Twenty years ago, careful examination of human chromosome 2 showed that it was the result of an ancient telomere to telomere fusion: 
The inverted arrangement of the 1TAGGG array and the adjacent sequences, which are similar to sequences found at present-day human telomeres, is precisely that predicted for a head-to-head telomeric fusion of two chromosomes...These data provide strong evidence that the inverted repeats in c8.1 arose from the head-to-head fusion of ancestral telomeres. [4]
One year later, further research showed evidence [5] of an ancient centromere in human chromosome 2, giving us evidence of both centromeric and telomeric remnant DNA which is what one would expect if human chromosome 2 was the product of a fusion event. This is no longer controversial in molecular biology. For example, a decade ago, researchers investigating the structure and evolution of human chromosome two noted in passing: 
Humans have 46 chromosomes, whereas chimpanzee, gorilla, and orangutan have 48. This major karyotypic difference was caused by the fusion of two ancestral chromosomes to form human chromosome 2 and subsequent inactivation of one of the two original centromeres (Yunis and Prakash 1982). As a result of this fusion, sequences that once resided near the ends of the ancestral chromosomes are now located in the middle of chromosome 2, near the borders of bands 2q13 and 2q14.1. For brevity, we refer henceforth to the region surrounding the fusion as 2qFus. Two head-to-head arrays of degenerate telomere repeats are found at this site; their head-to-head orientation indicates that chromosome 2resulted from a telomere to telomere fusion. (Emphasis mine). [6]
The evidence is unambiguous and irrefutable. Human chromosome 2 is the product of an ancient fusion of two ape-like chromosomes, as evidenced by the telomeric and centromeric remnant in the chromosome.  That chromosome 2 owes its origin to a fusion event is no longer in doubt. Recent papers on the subject tend to concentrate the specific details of when and how the fusion event took place. For example, Ventura et al in a 2012 paper in Genome Research proposed a model for how the fusion event occurred, and a scenario for the evolutionary history not only of human chromosome 2, but the two chromosomes that in chimps and gorillas did not fuse. The model proposed by Ventura et al is shown at the link below:

Ventura et al comment on their model:
"(C Anc) Catarrhine ancestor, (HCG Anc) human-chimpanzee-gorilla ancestor, (HC Anc) human-chimpanzee ancestor, (H Anc) human ancestor. 
(A) A pericentric inversion of chromosome IIq in the gorilla-chimpanzee ancestor (Yunis and Prakash 1982; Roberto et al. 2008; Ventura et al. 2011). 
(B) A segment of chromosome 10 was duplicatively transposed to the short arm of chromosome IIq in the common ancestor of human-chimpanzee-gorilla, placing it in close proximity to centromeric satellite sequences. 
(C ) A pericentric inversion that occurred on chromosome IIp in the human-chimpanzee ancestor (Wienberg et al. 1994; Roberto et al. 2008) internalizing the SatIII sequences. 
(D) A smaller local inversion in ancestral human-chimpanzee IIq placed the chromosome 2 segment adjacent to the StSat; StSat and potentially duplicated sequences spread to the distal end of the short arm of chromosome IIp in the human and chimpanzee ancestor. 
(E ) A fusion of IIp and IIq human ancestor created human chromosome 2 (Yunis and Prakash 1982; Wienberg et al. 1994) and squelched the spreading of StSat to human subtelomeric regions. [5]
Do we know the exact details of the fusion event and the evolutionary history of chromosome 2 and the unfused homologous chromosomes in chimps and apes? No, but we have a good idea of how it could have happened. Are we in doubt that a fusion event occurred? Not al all. The evidence is unambiguous and irrefutable. Human chromosome 2 is the product of an ancient fusion of two ape-like chromosomes, as evidenced by the telomeric and centromeric remnant in the chromosome. 

Cell biologist Kenneth Miller - who is also a Christian - summarises the reasons why the chromosomal fusion provides strong evidence of human-ape common ancestry:

The fused chromosome 2 exists in ancient hominids

One attempted rebuttal to this is that such chromosomal fusion events hinder fertility. This is not true. The molecular biologist Arthur Hunt points out that contrary to creationist assertions, such chromosomal translocations do not necessarily impact on fertility and quotes numerous examples of observed chromosomal translocations in mammals, and concludes that "it should be clear that [the creationist claims] are simply not reflective of the current thinking in mammalian cytogenetics." [7]

Genomic data from extinct hominids provides further support for the reality of human-ape common ancestry just from this line of evidence. Recently, DNA from a hominid bone found in the Denisova cave in Siberia was sequenced, showing that it came from a species closely related to the Neanderhals. It turns out that the Denisovan hominids also had the fused second chromosome. Palaeoanthropologist John Hawks quotes the researchers, noting that:
Sometime in our evolution, two separate chromosomes fused into one, giving us a karyotype of 46 chromosomes where chimpanzees, bonobos and gorillas have 48chromosomes. The high-coverage genome was sufficient to show that Denisova shared the human fusion: 
"Of more relevance may be examination of aspects of the Denisovan karyotype. The great apes have 24 pairs of chromosomes while humans have 23. This difference is caused by a fusion of two acrocentric chromosomes that formed the metacentric human chromosome 2 , and resulted in the unique head-to-head joining of the telomeric hexameric repeat GGGGTT. A difference in karyotype would likely have reduced the fertility of any offspring of Denisovans and modern humans. We searched all DNA fragments sequenced from the Denisovan individual and identified twelve fragments containing joined repeats. By contrast, reads from several chimpanzees and bonobos failed to yield any such fragments. We conclude that Denisovans and modern humans (and presumably Neandertals) shared a karyotype consisting of 46 chromosomes." 
We still have no idea whether this fusion made any difference to any phenotype in ancient humans. 
Many, many people have written me over the years to ask whether this fusion of two ancestral chromosomes might have been important to our evolution. Perhaps, many suggested, if Neandertals had a chromosomal incompatibility with us, that would explain why they became extinct. I have always doubted this, but without information it was impossible to be certain. 
It's nice to now have the information in hand: This fusion happened earlier in our evolution. [8]
This poses a huge problem for special creationists. Why would God not only create humans with chromosome 2 looking like the product of a fusion of two ape chromosomes, but do the same thing to an extinct species of humans who lived thouisands of years before Adam (assuming we place Adam around the time animals and plants were domesticated in the ANE)? Common descent solves this problem neatly - the Denisovans and Homo sapiens share a common ancestor in which he chromosomal fusion took place. Special creationists have no credible answer.


1. Myers, P. "Synteny: Inferring ancestral genomes.Nature Education (2008) 1(1):47
2. Falk D, Venema D "Signature in the Synteny" BioLogos Blog April 19 2010
3. Yunis J.J. Prakash O, "The origin of man: a chromosomal pictorial legacy". Science (1982) 215:1525–1530.
4. IJdo JW, Baldini A, Ward DC, Reeders ST, Wells RA, Origin of human chromosome 2: an ancestral telomere-telomere fusion. Proc Natl Acad Sci USA (1991) 88:9051-5
5.  Avarello R et al "Evidence for an ancestral alphoid domain on the long arm of human chromosome 2" Hum Genet (1992) 89:247-9
6. Fan Y, Linardopoulou E, Friedman C, et al  "Genomic Structure and Evolution of the Ancestral Chromosome Fusion Site in 2q13–2q14.1 and Paralogous Regions on Other Human Chromosomes" Genome Res. 2002 12:1651-1662
7. Hunt A "The Rise of Chromosome 2: The Fertility Problem" The Panda's Thumb February 8th 2009 
8. Hawks, J "The fused chromosome 2 was in Denisova" John Hawks Weblog 1st Sep 2012