Thursday, December 10, 2015

Dog genome ruminations

The other day I was re-reading the original dog genome paper, as you do. This is the paper published in 2005 to accompany the release of the first full dog genome sequence (of a boxer named Tasha) and accompanying annotation (a mapbook of what genes are located where in the very long sequence of bases that is the genome).

You might think that a genome paper wouldn’t be very interesting, because basically the point of it is to say “here is this genome. We published it. It was a lot of work, and it’s done, and now you can use it.” But most groups try to have something interesting to say in their descriptions of a new genome, and this one actually had a lot of interesting stuff about dog genomics in it.

Don’t just take my word for it. It’s open access, so you can read it for yourself.

Lindblad-Toh, Kerstin, et al. “Genome sequence, comparative analysis and haplotype structure of the domestic dog.” Nature 438.7069 (2005): 803-819.

The dog was one of the earlier mammals to be sequenced, so a lot of this paper consists of comparisons between dog and the other sequences we had at the time, human and mouse. We already knew that humans and mice were more closely related than humans and dogs in one sense: they share a most recent common ancestor. This means that as you follow the branches (and tangles) of the tree of life, first you get a branch that divides the most recent common ancestors of human, mouse, dog, and relatives from species like opossum and chicken; then you get a branch that divides the most recent common ancestors of human and mouse and relatives from dog and relatives; and only then do you get a branch that divides the most recent common ancestors of human and mouse. It looks like this:

Tirindelli, Roberto, et al. "From pheromones to behavior." Physiological reviews 89.3 (2009): 921-956. Fig 5
So we’d expect that human and mouse would share more genomic sequence than dog and human, right? Each of those branches in the tree of life represent a point at which one species becomes two, with resulting divergence in genomic sequence. So if the species divergence between humans and mice happened more recently than the species divergence between humans and dogs, then the genomes of humans and mice should look more similar than the genomes of humans and dogs. But it turns out, as this dog genome introductory paper reports, that dog and human share more genomic sequence, more base pairs, than human and mouse do. So how can that be, if humans and mice are closer together on the branches of the tree?

There are several forces contributing to this result, but the one that made me smile was the different rates at which each species reproduces. In the time since humans, mice, and dogs branched off from their shared common ancestor (before humans and mice branched off from their shared common ancestor), mice have had many more generations than humans and dogs. They reproduce so quickly compared to us and dogs that they have more chances to change their genetics from generation to generation. And as a result, while the number of divisions (places where the tree branches) are greater between human and dog than human and mouse, the number of generations of mice between today’s mouse and that last common ancestor of mice and humans and dogs is greater in mice than in dogs or humans. As the paper’s authors put it:

The lineage-specific divergence rates (human < dog < mouse) are probably explained by differences in metabolic rates or generation times, but the relative contributions of these factors remain unclear.

The other way of looking at it is saying that species age at different rates. So while behaviorally modern humans appeared around 50,000 years ago, and dogs appeared arguably 10,000-32,000 years ago, nevertheless the human population is about 4,000 generations old while the dog population is around 9,000 generations old. Because dog generations are shorter.

We created them, but they’re now older than us. Just like how my dog was younger than me when I got him, but aged right past me. Science!

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