I’m still doing quick mining of the Denisova sequence for obvious things. One of the simplest is the polymorphism in microcephalin (MCPH1) that Evans and colleagues
The polymorphism, entered in dbSNP as rs930557, is a single nucleotide mutation that changes the ancestral aspartate to a derived histidine. The derived allele, called the “D” allele, is linked to a fairly long haplotype, which Evans and colleagues
The evidence for possible introgression is the unusual paucity of recombination in the period before this putative selection commenced. I wrote about this in 2006 (“Introgression and microcephalin FAQ”). The polymorphism looks very old, by virtue of the high density of linked mutations around it at the sequence level. They estimated the tree root at around 1.8 million years ago. This is not too extreme compared to other loci (between twice and three times the average and well within the expected tail) but the suppression of recombination does seem unusual. Balancing selection on a region where recombination was physically difficult, such as a chromosomal inversion, would be one possible evolutionary history that could give rise to this pattern, but there is no sign of such a feature here. The other candidate is ancient, strong population structure. That was the interpretation favored by Evans and colleagues
Evans and coworkers suggested Neandertals as a possible population from which the derived allele had originated. This seemed likely on the basis of its widespread geographic distribution outside Africa. But the relevant nucleotide of MCPH1 is now known from at least two Neandertals, neither of which show the derived allele. Martina Lari and colleagues
The Denisovans might seem an unlikely source for the derived MCPH1 variant, because the genetic contribution of this population to most living Eurasians was at most slight. But as we pointed out in a 2006 paper
For the Denisova genome, that’s where we have come. The public data release includes three sequence reads across rs930557, all of which include the ancestral (G) nucleotide. That’s not complete evidence about the individual’s genotype nor does it exclude the presence of the derived allele in the population. But there it is, for what it’s worth.
After the population model presented by Reich and colleagues
Maybe there were yet other ancient populations that remain unsampled, contributing to the genealogical depth of some gene loci outside Africa. One of our current challenges is the disconnect between the genome data and fossil and archaeological comparisons. We’re working to apply some archaeologically-informed models of population structure to genomic variation from living humans, to find the hidden traces of ancient population structure. As I noted (“The Denisova genome FAQ”), the signs of interbreeding with Denisovans were apparent in the existing samples from Papua New Guinea, even before the ancient genome was available. Smaller fractions of intermixture will be harder to find, but we now know what to look for, and we’ll soon have much larger samples to work with.
Clearly we have a lot of work ahead of us. An average four percent contribution of some archaic human population to living people implies that substantially more than four percent of loci will be affected by such interbreeding on one person or another. The fraction of affected loci could be as large as 100% (all Neandertal genes persisting in somebody living today). To the extent that it is actually smaller, this fraction will provide substantial information about population history. To do this comparison well, we’ll need much larger samples of genomes of living humans – substantially beyond the 1000 Genomes Project.