The Pith: You are expected to have 30 new mutations which differentiate you from your parents. But, there is wiggle room around this number, and you may have more or less. This number may vary across siblings, and explain differences across siblings. Additionally, previously used estimates of mutation rates which may have been too high by a factor of 2. This may push the “last common ancestor” of many human and human-related lineages back by a factor of 2 in terms of time.
There’s a new letter in Nature Genetics on de novo mutations in humans which is sending the headline writers in the press into a natural frenzy trying to “hook” the results into the X-Men franchise. I implicitly assume most people understand that they all have new genetic mutations specific and identifiable to them. The important issue in relation to “mutants” as commonly understood is that they have salient identifiable phenotypes, not that they have subtle genetic variants which are invisible to us. Another implicit aspect is that phenotypes are an accurate signal or representation of high underlying mutational load. In other words, if you can see that someone is weird in their traits, presumably they are rather strange in their underlying genetics. This is the logic behind models which assume that mutational load has correlates with intelligence or beauty, and these naturally tie back into evolutionary rationales for human aesthetic preferences (e.g., “good genes” models of sexual selection).
J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline…Diverse studies have supported Haldane’s contention of a higher average mutation rate in the male germline in a variety of mammals, including humans…Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families.
Last summer I made a thoughtless and silly error in relation to a model of human population history when asked by a reader the question: “which population is most distantly related to Africans?” I contended that all non-African populations are equally distant. This is obviously wrong on the face of it if you look at any genetic distance measures. West Eurasians, even those without recent Sub-Saharan African admixture (e.g., North Europeans) are closer than East Eurasians, who are often closer than Oceanians and Amerindians. One explanation I offered is that these latter groups were subject to greater genetic drift through a series of population bottlenecks. In this framework the number of generations until the last common ancestor with Sub-Saharan Africans for all groups outside of Africa should be about the same, but due to evolutionary factors such as more extreme genetic drift or different selective pressures some non-African groups had diverged more from Africans than others in terms of their genetic state. In other words, the most genetically divergent groups in relation to Africans did not diverge any earlier, but simply diverged more rapidly.
Dienekes Pontikos disagreed with such a simple explanation. He argued that admixture or gene flow between Africans and non-African groups since the last common ancestor could explain the differences. I am now of the opinion that Dienekes may have been right. My own confidence in the “serial bottleneck” hypothesis as the primary explanation for the nature of relationships of the phylogenetic tree of human populations is shaky at best. Why my errors of inference?
There were two major issues at work in my misjudgments of the arc of the past and the topology of the present. In the latter instance I saw plenty of phylogenetic trees which illustrated clearly the variation in genetic distance from Africans for various non-African groups. Why didn’t I internalize those visual representations? It was I think the power of the “Out of Africa” (OoA) with replacement paradigm. Even by the summer of 2010 I had come to reject it in its strong form, due to the evidence of admixture with Neanderthals, and rumors of other events which were born out to be true with the publishing of the Denisovan results. But to a first approximation the clean and simple OoA was still looming so large in my mind that I made the incorrect inference, whereby all non-Africans are viewed simply as a branch of Africans without any particular differentiation in relation to their ancestral population. Secondarily, I also was still impacted by the idea that most of the genetic variation you see in the world around us has its roots tens of thousands of years ago. By this, I mean that the phylogeographic patterns of 25,000 years in the past would map on well to the phylogeographic patterns of the present. This assumption is what drove a lot of phylogeography in the early aughts, because the chain of causation could be reversed, and inferences about the past were made from patterns of the present. My own confidence in this model had already been perturbed when I made my errors, but it still held some sort of sway in my head implicitly I believe. It is one thing to move on from old models explicitly, but another thing to remove the furniture from your cognitive basement and attic.
I have moved further from my preconceptions between then and now. It took a while to sink in, but I’m getting there. A cognitive “paradigm shift” if you will. In particular I am more open to the idea of substantive back migration to Africa, as well as secondary migrations out of Africa. A new paper in Genome Research is out which adds some interesting details to this bigger discussion, and seems to weigh in further against my tentative hypothesis that serial bottlenecks and genetic drift can explain variation in distance to Africans of various non-African groups. Human population dispersal “Out of Africa” estimated from linkage disequilibrium and allele frequencies of SNPs: