What Separates Humans from Egg-layers?

Part of what makes the platypus seem strange is that it lays eggs--like amphibians, reptiles, and birds--and yet it is a mammal. In contrast, like many other mammals we give birth to live young which receive nourishment during development by means of a placenta instead of from egg yolk. We have no need for the yolk protein vitellogenin; we don't make it, nor do we have the gene (or genes--there can be multiple copies) for it. The presence of vitellogenin sets egg-laying animals apart from us placentals. Or if you want to put it the other way, the absence of vitellogenin separates us from egg-layers. But there is more to the story, of course.

A quick digression: Did you know that when you 'delete' a file on a computer disk, what you have really done is tell the operating system not to recognize the file anymore? The data in the file remains on the disk until the space is overwritten by a different file. In fact there are programs that can find and resurrect deleted files.

Genomes can be like that and, wouldn't you know it, the remains of vitellogenin are in our genome, as well as the genomes of other placental animals. Genes that have become broken and degraded by mutation are called pseudogenes, and there are bits and pieces of between one and three vitellogenin pseudogenes in the human genome. (The number is debatable because two of the copies are degraded to the point of being difficult to statistically distinguish from background sequence.) Perhaps the clearest illustration of this is Figure S2 from Brawand et al, which shows an alignment of a portion of one of the vitellogenin genes (VIT1) from four species. (Click for larger view.)

Figure S2. Sequence Alignment of the VIT1 Exon 3 from Human (Homo sapiens), Dog (Canis familiaris), Armadillo (Dasypus novemcinctus), and Chicken (Gallus gallus). The alignment shows two indels that are shared between human, dog, and armadillo, indicating inactivation of these genes in the common ancestor of these species (see main text for discussion).

The figure shows an alignment of sequences from the genome of chicken, human, dog, and armadillo, with chicken as the standard of comparison (since it's VIT1 gene is in tact.) I added the green arrows to draw attention to the deletions shared by human, dog, and armadillo. That the deletions are shared by all three suggests that they occurred in common ancestors, and that this was a pseudogene before the lineages that gave rise to the three species diverged. The asterisks indicate positions where all four sequences are identical.

Now the genome is a big place, and you could argue that if you search hard enough you will find a spurious sequence that yields some alignment to the chicken vitellogenin genes. However, the authors also found alignment in the sequences flanking the VIT genes, which provides added support to the authenticity of the alignment. This is represented in Figure 2 as a dot plot comparing human and chicken sequence. (Click for larger view.)

Figure 2. Genome Alignment (Dot Plot Representing SIM Alignments) of Human/Chicken Syntenic Regions VIT 1-VIT3 Regions. The chain with the best cumulative score is shown. Alignment of flanking genes confirms the synteny of the aligned regions. The combined alignments of VIT1 coding sequences showed significantly higher alignment scores than the genomic background (introns and intergenic regions) in the chain, as assessed by a Mann-Whitney U test (p < 0.05). Thus, we can statistically exclude that detected VIT1 remnants from humans represent spurious sequence matches. The coding sequence matches for VIT2/3 may be too short to provide statistical significance or partially spurious.

Black dots represent identical sequence, and you can see--especially in the top panel--that there is some significant alignment with not only VIT1, but with ELTD1 as well. So not only do portions of the VIT genes align, but they are found in the same context relative to other genes. Again, this gives added support to their authenticity.

So the presence/absence of vitellogenin indeed sets us apart from egg-laying animals. But at the same time it paradoxically ties us together.


Reference:

Brawand D, Wahli W, Kaessmann H (2008) Loss of Egg Yolk Genes in Mammals and the Origin of Lactation and Placentation. PLoS Biol 6(3): e63

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