The Role of Geography in Human Adaptation

122

The relative importance of the roles of adaptation and chance in determining genetic diversity and evolution has received attention in the last 50 years, but our understanding is still incomplete. All statements about the relative effects of evolutionary factors, especially drift, need confirmation by strong demographic observations, some of which are easier to obtain in a species like ours. Earlier quantitative studies on a variety of data have shown that the amount of genetic differentiation in living human populations indicates that the role of positive (or directional) selection is modest. We observe geographic peculiarities with some Y chromosome mutants, most probably due to a drift-related phenomenon called the surfing effect. We also compare the overall genetic diversity in Y chromosome DNA data with that of other chromosomes and their expectations under drift and natural selection, as well as the rate of fall of diversity within populations known as the serial founder effect during the recent “Out of Africa” expansion of modern humans to the whole world. All these observations are difficult to explain without accepting a major relative role for drift in the course of human expansions. The increasing role of human creativity and the fast diffusion of inventions seem to have favored cultural solutions for many of the problems encountered in the expansion. We suggest that cultural evolution has been subrogating biologic evolution in providing natural selection advantages and reducing our dependence on genetic mutations, especially in the last phase of transition from food collection to food production.

Section: Discussionmentioning

confidence: 99%

Y chromosome diversity, human expansion, drift, and cultural evolution

Chiaroni

Underhill

Cavalli-Sforza

2009

122

“…Population differentiation of rs514182 suggests adaptive evolution of caspase-1 response. The map and bar graphs display the geographic distribution of imputed APIP rs514182 allele frequencies from the HGDP Selection Browser (74,75). Allele frequencies for the derived procell death allele in each continent are summarized to the right of bar graphs, with earlier adopters of agriculture shown in green.…”

Section: Resultsmentioning

confidence: 99%

“…Maps, bar graphs, and genotype frequencies for rs514182 and rs2043211 were downloaded from the Human Genome Diversity Project (HGDP) Selection Browser (74)(75)(76). Quantification of the correlation between allele frequency and geographic distribution (Europe and Asia vs. sub-Saharan Africa, the Americas, and Oceania) was conducted using bayenv (59).…”

Section: Methodsmentioning

confidence: 99%

Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death

Ko¹,

Gamazon

Shukla³

et al. 2012

Genome-wide association studies can identify common differences that contribute to human phenotypic diversity and disease. When genome-wide association studies are combined with approaches that test how variants alter physiology, biological insights can emerge. Here, we used such an approach to reveal regulation of cell death by the methionine salvage pathway. A common SNP associated with reduced expression of a putative methionine salvage pathway dehydratase, apoptotic protease activating factor 1 (APAF1)-interacting protein (APIP), was associated with increased caspase-1-mediated cell death in response to Salmonella. The role of APIP in methionine salvage was confirmed by growth assays with methionine-deficient media and quantitation of the methionine salvage substrate, 5′-methylthioadenosine. Reducing expression of APIP or exogenous addition of 5′-methylthioadenosine increased Salmonellae-induced cell death. Consistent with APIP originally being identified as an inhibitor of caspase-9-dependent apoptosis, the same allele was also associated with increased sensitivity to the chemotherapeutic agent carboplatin. Our results show that common human variation affecting expression of a single gene can alter susceptibility to two distinct cell death programs. Furthermore, the same allele that promotes cell death is associated with improved survival of individuals with systemic inflammatory response syndrome, suggesting a possible evolutionary pressure that may explain the geographic pattern observed for the frequency of this SNP. Our study shows that in vitro association screens of disease-related traits can not only reveal human genetic differences that contribute to disease but also provide unexpected insights into cell biology.HapMap | lymphoblastoid | pyroptosis | quantitative trait | polygenic adaptation

“…However, in contrast to the classic model, we also expect the presence of many incomplete selective sweeps. Indeed, the genomic signatures of such incomplete sweeps appear to be plentiful in a number of organisms (31)(32)(33). Incomplete sweeps also appear to be common in experimental evolution in Drosophila, where virtually no classic sweeps have been detected after 600 generations of evolution despite abundant evidence of phenotypic adaptation over this period (34).…”

Section: Discussionmentioning

confidence: 99%

Heterozygote advantage as a natural consequence of adaptation in diploids

Sellis¹,

Callahan

Petrov³

et al. 2011

186

200

Molecular adaptation is typically assumed to proceed by sequential fixation of beneficial mutations. In diploids, this picture presupposes that for most adaptive mutations, the homozygotes have a higher fitness than the heterozygotes. Here, we show that contrary to this expectation, a substantial proportion of adaptive mutations should display heterozygote advantage. This feature of adaptation in diploids emerges naturally from the primary importance of the fitness of heterozygotes for the invasion of new adaptive mutations. We formalize this result in the framework of Fisher's influential geometric model of adaptation. We find that in diploids, adaptation should often proceed through a succession of short-lived balanced states that maintain substantially higher levels of phenotypic and fitness variation in the population compared with classic adaptive walks. In fast-changing environments, this variation produces a diversity advantage that allows diploids to remain better adapted compared with haploids despite the disadvantage associated with the presence of unfit homozygotes. The short-lived balanced states arising during adaptive walks should be mostly invisible to current scans for long-term balancing selection. Instead, they should leave signatures of incomplete selective sweeps, which do appear to be common in many species. Our results also raise the possibility that balancing selection, as a natural consequence of frequent adaptation, might play a more prominent role among the forces maintaining genetic variation than is commonly recognized.A daptation by natural selection is the key process responsible for the fit between organisms and their environments. The invasion of new adaptive mutations is an essential component of this process that fundamentally differs between haploid and diploid populations. In diploids, while a new mutation is still rare, natural selection acts primarily on the mutant heterozygote (1). As a result, only those adaptive mutations that confer a fitness advantage as heterozygotes have an appreciable chance of invading the population ("Haldane's sieve"). However, if the heterozygote of an invading adaptive mutation is fitter than the mutant homozygote, the mutation will not be driven to fixation but, instead, maintained at an intermediate, balanced frequency.We argue that heterozygote advantage should be very common during adaptation in diploids if selection is stabilizing and at least some mutations are large enough to overshoot the optimum. Consider, for example, adaptation through changes in gene expression (Fig. 1A), which is an important, if not the dominant, mechanism of adaptation (2). Here, mutations of small effect (Fig. 1B) will be adaptive when they modify expression in the adaptive direction whether the organism is haploid or diploid. However, mutations of large effect (Fig. 1C) can be nonadaptive in haploids, because they overshoot the optimum, yet be adaptive in diploids, because their phenotypic effect is moderated when heterozygous. These mutations will have heterozy...