Positive Selection in East Asians for an EDAR Allele that Enhances NF-κB Activation

Bryk, Jarosław; Hardouin, Emilie A.; Pugach, Irina; Hughes, David A.; Strotmann, Rainer; Stoneking, Mark; Myles, Sean

doi:10.1371/journal.pone.0002209

Cited by 92 publications

(107 citation statements)

References 47 publications

(60 reference statements)

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“…This is likely an unrealistic scenario in human populations, where positive selection is perhaps less common (Hernandez et al 2011). However, some have argued that selection may be pervasive in the human genome as well (Boyko et al 2008;Enard et al 2014), and certainly humans show many adaptations to local environments (e.g., Li et al 2007;Perry et al 2007;Tishkoff et al 2007;Barreiro et al 2008;Bryk et al 2008). Thus while it seems unlikely that every site in the genome would be affected by linked selection, some currently unknown subset of sites must be, and thus we should expect demographic estimation to be subject to some degree of bias (perhaps negligible in well-designed studies; see below).…”

Section: Discussionmentioning

confidence: 99%

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

2016

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The availability of large-scale population genomic sequence data has resulted in an explosion in efforts to infer the demographic histories of natural populations across a broad range of organisms. As demographic events alter coalescent genealogies, they leave detectable signatures in patterns of genetic variation within and between populations. Accordingly, a variety of approaches have been designed to leverage population genetic data to uncover the footprints of demographic change in the genome. The vast majority of these methods make the simplifying assumption that the measures of genetic variation used as their input are unaffected by natural selection. However, natural selection can dramatically skew patterns of variation not only at selected sites, but at linked, neutral loci as well. Here we assess the impact of recent positive selection on demographic inference by characterizing the performance of three popular methods through extensive simulation of data sets with varying numbers of linked selective sweeps. In particular, we examined three different demographic models relevant to a number of species, finding that positive selection can bias parameter estimates of each of these models-often severely. We find that selection can lead to incorrect inferences of population size changes when none have occurred. Moreover, we show that linked selection can lead to incorrect demographic model selection, when multiple demographic scenarios are compared. We argue that natural populations may experience the amount of recent positive selection required to skew inferences. These results suggest that demographic studies conducted in many species to date may have exaggerated the extent and frequency of population size changes.KEYWORDS population genetics; positive selection; demographic inference T HE widespread availability of population genomic data has spurred a new generation of studies aimed at understanding the histories of natural populations from a host of model and nonmodel organisms alike. In particular, genomescale variation data allows for inference of demographic factors such as population size changes, the timing and ordering of population splits, migration rates between populations, and the founding of admixed populations (Pool et al. 2010;Pickrell and Pritchard 2012;Sousa and Hey 2013). Such efforts can refine our picture of demographic events inferred from the archaeological record (e.g., Fagundes et al. 2007;Goebel et al. 2008), or reveal such events in species where no archaeological data are available, and can aid conservation efforts by complementing census data (e.g., Hájková et al. 2007;Garrick et al. 2015).Population genomic data sets are well suited for this task simply because demographic changes leave their mark on patterns of genetic variation. Recent population growth, for example, will result in an excess of rare variation compared to equilibrium expectations (Fu 1997), while population contraction will result in an excess of intermediate frequency alleles (Maruyama and Fuerst 198...

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Section: Discussionmentioning

confidence: 99%

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

2016

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“…40,41 The 370A allele reportedly has a more potent signaling activity than the 370V allele in vitro. 42,43 Therefore, it is supposed that the strong activity of the 370A causes a high prevalence of hypoconulid in the AA genotype. However, the possibility that another polymorphism in strong LD with EDAR 370V/R is responsible for the phenotypic variation has not been completely denied.…”

Section: Discussionmentioning

confidence: 99%

Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits

et al. 2012

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Dental morphology is highly diverse among individuals and between human populations. Although it is thought that genetic factors mainly determine common dental variations, only a few such genetic factors have been identified. One study demonstrated that a nonsynonymous single-nucleotide polymorphism (370V/A, rs3827760) in the ectodysplasin A receptor gene (EDAR) is associated with shoveling and double-shoveling grades of upper first incisors and tooth crown size. Here, we examined the association of EDAR 370V/A with several dental characters in Korean and Japanese subjects. A meta-analysis that combined analyses of Korean and Japanese subjects revealed that the Asian-specific 370A allele is associated with an increase in the grades of shoveling and double shoveling, as previously found. We also showed a highly significant association between EDAR 370V/A genotype and crown size, especially mesiodistal diameters of anterior teeth. Moreover, we found that the 370A allele was associated with the presence of hypoconulids of lower second molars. These results indicated that the EDAR polymorphism is responsible, in part, for the Sinodonty and Sundadonty dichotomy in Asian populations, and clearly demonstrated that the EDAR polymorphism has pleiotropic effects on tooth morphology. As the 370A allele is known to be a most likely target of positive selection in Asian populations, some phenotypes associated with the variant may be 'hitchhiking phenotypes', while others may be actual targets of selection.

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“…The functional annotations of genes identified in large-scale scans (e.g., 68) flag many as potentially of significance in disease resistance or dietary adaptations. As the vast task of identifying the functions of many genes proceeds, we anticipate many similar cases to emerge (112)(113)(114).…”

Section: Current Evidence and Problems To Solvementioning

confidence: 99%

Gene-culture coevolution in the age of genomics

Richerson

Boyd

Henrich

2010

Proc. Natl. Acad. Sci. U.S.A.

287

198

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The use of socially learned information (culture) is central to human adaptations. We investigate the hypothesis that the process of cultural evolution has played an active, leading role in the evolution of genes. Culture normally evolves more rapidly than genes, creating novel environments that expose genes to new selective pressures. Many human genes that have been shown to be under recent or current selection are changing as a result of new environments created by cultural innovations. Some changed in response to the development of agricultural subsistence systems in the Early and Middle Holocene. Alleles coding for adaptations to diets rich in plant starch (e.g., amylase copy number) and to epidemic diseases evolved as human populations expanded (e.g., sickle cell and G6PD deficiency alleles that provide protection against malaria). Large-scale scans using patterns of linkage disequilibrium to detect recent selection suggest that many more genes evolved in response to agriculture. Genetic change in response to the novel social environment of contemporary modern societies is also likely to be occurring. The functional effects of most of the alleles under selection during the last 10,000 years are currently unknown. Also unknown is the role of paleoenvironmental change in regulating the tempo of hominin evolution. Although the full extent of culture-driven gene-culture coevolution is thus far unknown for the deeper history of the human lineage, theory and some evidence suggest that such effects were profound. Genomic methods promise to have a major impact on our understanding of gene-culture coevolution over the span of hominin evolutionary history.T he human cultural system supports the cumulative evolution of complex adaptations to local, often ephemeral environments. Using elaborate technology and depending on large bodies of cultural knowledge about plants and animals, stone-age foragers spread to a much wider range of habitats than any other mammal, from the frigid tundra in the Arctic to the arid deserts of Australia. The Polynesian outrigger canoe and the Arctic kayak are examples of the astoundingly sophisticated cultural adaptations that people have used to occupy distant corners of the globe. The forms of social organizations observed in humans are more diverse than the rest of the primate order combined. Humans constitute one of the world's most impressive adaptive radiations. We have occupied virtually every habitat on earth by using technology and social organization to generate thousands of socioeconomic systems (1, 2). Cultural Evolution and Gene-Culture CoevolutionCulture has many definitions, but for our purposes a useful one is all of the information that individuals acquire from others by a variety of social learning processes including teaching and imitation (3). Transmission fidelity is often sufficiently high for culture to act as an inheritance system (4). We commonly observe that the ideas, practices, skills, attitudes, norms, art styles, technology, ways of speaking, and other elements...

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Positive Selection in East Asians for an EDAR Allele that Enhances NF-κB Activation

Cited by 92 publications

References 47 publications

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

Effects of an Asian-specific nonsynonymous EDAR variant on multiple dental traits

Gene-culture coevolution in the age of genomics

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