Universal common ancestry in the hotseat II

The Vitellogenin Pseudogene Story: Unequally Yolked

Ann Gauger

Synteny refers to how well chromosomal sequences from different species align with one another. Genes can be in the same general order and location between species, for example rat and mouse, or chimp and human. If they align well, evolutionists take the alignment as evidence for common ancestry. Sometimes, the gene sequences may be interrupted by deletions or insertions, and stop codons, which prevent the gene from making functional protein.

These "inactivated" genes are calledpseudogenes, and are taken by evolutionists as further evidence for common descent. Their presence is explained as the remnants of once functional genes broken by mutation and no longer needed by the organism.

"Why should a designer litter the genome with so much trash?" the evolutionists say.

One particular story that combines ancient pseudogenes and synteny to argue for common descent is circulating on the web, right now. See here for comments yesterday by Evolution Newson "Functional Pseuodogenes and Common Descent." The story is several years old, but it's popular because it seems to confirm the old evolutionary idea that our long ago ancestors were egg-laying creatures that then evolved to live-bearing placental mammals. And it's being challenged because of new evidence coming from ENCODE and other genome projects.

Egg-bearing animals use proteins called vitellogenins to transport nutrients in their egg yolk. Each vitellogenin is a very long complicated protein composed of many exons (stretches of DNA that must be copied into RNA and then spliced together into one contiguous piece before being translated into vitellogenin). An article by Dennis Venema lays out the supposed story: humans retain the remnants of DNA that used to code for egg yolk proteins called vitellogenins. Since humans don't lay eggs, the argument goes, these "vitellogenin" pseudogenes, now long since mutated into near unrecognizability, must be inherited from common ancestors who did lay eggs. Venema claims that all three human "vitellogenin" pseudogenes, VIT1 through VIT3, show traces of sequence similarity to the functioning vitellogenin genes of the chicken.

All of this argument depends on three ideas: 1) we share common ancestry with egg laying animals, 2) any sequence similarity is due to ancestry not function, and 3) there was just one function for the vitellogenin gene, and that was making vitellogenin. Any function now is due to secondarily evolved function.

This story is based on a 2008 paper by Brawand et al. that discusses yolk proteins in egg-laying animals and mammals. In that paper they identified the region of the chicken genome where vitellogenin genes are located, then found the similar regions in humans, dogs, and various marsupials and platypus, to see if vitellogenin pseudogenes could be found in the right syntenic neighborhoods.

Patches of sequence similarity to the chicken genome that might be interpreted as pseudogenes can be found in syntenic regions of marsupial genomes. Evidence for vitellogenin pseudogenes in human and dog genomes, on the other hand, is very weak. It is practically nonexistent for vitellogenin genes VIT2 and VIT3 (it is not statistically significant compared to the genomic background). The remaining gene, VIT1, has two patches of similarity in its putative former coding sequence, according to a supplemental figure in the paper.

The best of them is a patch 150 bases long (out of 42,637 total bases for the gene!) that has roughly 50 percent identity, by my estimation, and a few deletions to help make things match up. According to the authors, there is a 95 percent chance that the amount of similarity between VIT1 for humans and dogs, and the chicken VIT1, is not due to random chance -- but that's just at the borderline for statistical significance. (They don't specify exactly what sequences they were comparing, so I am guessing it was the one whose sequence they reported in the paper.)

So what if the similarity is statistically significant? What apparent similarity there is could well be due to an overlapping gene with an entirely different function that is present in that stretch of sequence in the chicken, marsupial, dog, and human genomes. (I am guessing it is present in the other genomes -- I know it is present in humans.) Indeed, there is evidence of another gene with other possible functions in that region of the genome. As reported byTomkins:

...the alleged vtg [vitellogenin] fragment in human is not a pseudogene remnant at all, but a functional enhancer element in the fifth intron of a "genomic address messenger" (GAM) gene. This GAM gene produces long noncoding RNAs that have been experimentally shown to selectively inhibit the translation of known target genes, a majority of which are implicated in a variety of human diseases. Messenger RNAs from this gene are also expressed in a variety of human brain tissues. The alleged 150 base vtg sequence contains a variety of highly conserved mammalian transcription factor binding domains, nucleosome depleted open-active chromatin, is hypo-methylated, associates with RNA polymerase 2 in long-range chromatin interactions, and binds the Mafk transcriptional regulator. These combinatorial data clearly show that it is a functional enhancer element in a GAM gene expressed in the human brain -- strongly challenging the idea that this sequence is an egg-laying pseudogene genomic fossil.The long non-coding RNAs mentioned above are widely believed to have many important regulatory functions in the cell. They are implicated in long- and short-range interactions between genes, the way the DNA loops, whether genes are sequestered or not -- all these things and more are affected.

Let's summarize some of the main points we have discussed:

1. A similar arrangement of genes exists among mammalian genomes and the chicken genome in the neighborhood of the chicken vitellogenin genes, with the very important exception that in mammals, the vitellogenin genes are either absent or pseudogenized.
2. This similar order could be due to ancestry or functional reasons.
3. In humans the evidence for a vitellogenin pseudogene fragment is very weak.
4. It is possible that any sequence similarity there might be due to a shared function, because of the regulatory gene that exists in the same region. (This despite Venema's disparaging comments to the contrary. See above.)
5. If the sequence similarity is due to function, then it need not indicate common ancestry, or the former presence of an egg-laying protein in the human genome --
6. That is, if there is sufficient sequence similarity to make the claim in the first place.
7. Claiming exaptation, à la Venema, is a post hoc argument based on the prior assumption of common descent. It goes like this:
1. There is sequence similarity to vitellogenins in the human genome.
2. It must be due to common descent.
3. There is evidence of another possible function for the sequence.
4. It must have evolved as a secondary function, because we know that it was originally vitellogenin.
8. Claiming a functional reason for the similarity is a creationist dodge.
9. Claiming exaptation sounds like a dodge to me.