Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage

Abstract

At the center of the debate on the emergence of modern humans and their spread throughout the globe is the question of whether archaic Homo lineages contributed to the modern human gene pool, and more importantly, whether such contributions impacted the evolutionary adaptation of our species. A major obstacle to answering this question is that low levels of admixture with archaic lineages are not expected to leave extensive traces in the modern human gene pool because of genetic drift. Loci that have undergone strong positive selection, however, offer a unique opportunity to identify low-level admixture with archaic lineages, provided that the introgressed archaic allele has risen to high frequency under positive selection. The gene microcephalin (MCPH1) regulates brain size during development and has experienced positive selection in the lineage leading to Homo sapiens. Within modern humans, a group of closely related haplotypes at this locus, known as haplogroup D, rose from a single copy Ϸ37,000 years ago and swept to exceptionally high frequency (Ϸ70% worldwide today) because of positive selection. Here, we examine the origin of haplogroup D. By using the interhaplogroup divergence test, we show that haplogroup D likely originated from a lineage separated from modern humans Ϸ1.1 million years ago and introgressed into humans by Ϸ37,000 years ago. This finding supports the possibility of admixture between modern humans and archaic Homo populations (Neanderthals being one possibility). Furthermore, it buttresses the important notion that, through such adminture, our species has benefited evolutionarily by gaining new advantageous alleles. The interhaplogroup divergence test developed here may be broadly applicable to the detection of introgression at other loci in the human genome or in genomes of other species. human evolution ͉ introgression ͉ admixture

European early modern humans and the fate of the Neandertals

“…Yet, the overwhelming phenetic and cladistic modernity of these EEMH (and Gravettian) human remains indicates that the majority of their ancestry was that of the MPMHs. Indeed, this is the pattern that is also emerging from current interpretations of the human molecular record, both extant (8,9,54) and ancient (55,56), despite the small sample sizes used in most of the latter analyses.…”

Inferring Past Demography Using Spatially Explicit Population Genetic Models

“…Based on these data, simple descriptive approaches have shown that the distance from East Africa is a good predictor of the genetic diversity in human populations worldwide (Handley et al 2007;Ramachandran et al 2005), making geography a better determinant of human genetic differentiation than ethnicity . These studies have strengthened the case for the recent African origin (RAO) model of human evolution, as opposed to alternative models, such as the multiregional evolution model (Wolpoff et al 2000) or some forms of assimilation models in which modern humans migrating outside Africa hybridized with local Homo erectus and incorporated old lineages (Eswaran et al 2005;Evans et al 2006). Using a Bayesian framework, we have been able to statistically assess the relative probabilities of different fl avors of all these models using DNA data from 50 nuclear loci sequenced in African, Asian, and native American samples (Fagundes et al 2007).…”

“…A possible example of such a problem are two genes involved in the control of brain size, MCPH1 and ASPM (Evans et al 2006;Mekel-Bobrov et al 2005), which show an increased frequency of a derived haplotype outside Africa, interpreted to be the consequence of local positive selection for increased cognitive abilities in non-African populations. However, the link between the presence of the derived haplotype and a phenotypic trait could not be found (Dobson-Stone et al 2007;Mekel-Bobrov et al 2007;Timpson et al 2007;Woods et al 2006;Yu et al 2007).…”

Les prémices du génome de Néandertal

“…Le fait que le chromosome X de Néandertal ait un degré de divergence plus important que celui des autosomes tendrait à montrer que les croisements auraient eu lieu de façon unilatérale : les humains mâles auraient engendré des enfants avec des femmes néandertaliennes. À l'inverse, dans un récent article [19], B.T. Lahn et al semblent suggérer le contraire : le gène de la microcéphaline (MCPH1), supposé réguler la taille du cerveau chez l'homme, posséderait de nombreux haplogroupes ; parmi ceux-ci, l'haplogroupe D, très ancien, aurait été réintroduit récemment (il y a environ 37 000 ans) chez les humains modernes par… qui sait ?…”