Recent human adaptation: genomic approaches, interpretation and insights

Abstract

The recent availability of genomic data has spurred many genome-wide studies of human adaptation in different populations worldwide. Such studies have provided insights into novel candidate genes and pathways that are putatively involved in adaptation to different environments, diets and disease prevalence. However, much work is needed to translate these results into candidate adaptive variants that are biologically interpretable. In this Review, we discuss methods that may help to identify true biological signals of selection and studies that incorporate complementary phenotypic and functional data. We conclude with recommendations for future studies that focus on opportunities to use integrative genomics methodologies in human adaptation studies.

Distance from sub-Saharan Africa predicts mutational load in diverse human genomes

“…Recent genome-wide studies have stressed the paucity of selective sweeps in the human genome (35,58,59); only 0.5% of nonsynonymous mutations in 1000 Genomes Pilot Project were identified has having undergone positive selection. Others have emphasized evidence for pervasive adaptive selection (60,61) and a variety of studies have identified specific beneficial alleles locally adapted to high altitude, immune response, and pigmentation (62)(63)(64). We considered local adaptive evolution by examining highly differentiated alleles in our dataset, that is, alleles that differ by 80% in frequency between a pair of populations, indicative of a strong local adaptation.…”

Human high-altitude adaptation: forward genetics meets the HIF pathway

“…For well over a century, the unique suite of physiological adaptations to chronic hypoxia observed among long-term resident populations has been well documented (for review, see Hornbein and Schoene 2001). Studies conducted over the past decade as well as more recent genomic studies support a genetic basis for these adaptations (Simonson et al 2012;Scheinfeldt and Tishkoff 2013). Interestingly, the patterns of genetic changes differ among the three populations.…”

“…This interaction of genes determining highaltitude-adaptive phenotypes may be contrasted with other well-known examples of recent human evolution in which selection appears to have acted on single genes. Examples of this would include the selection of a Lactase (LCT) gene variant to allow lactase persistence in European populations and the selection of an EDAR variant to produce a constellation of findings related to ectodermal development in Asian populations (Kamberov et al 2013;Scheinfeldt and Tishkoff 2013). High-altitude adaptation may be more like skin color determination, in which multiple interacting loci determine phenotype (Sturm 2009).…”

The cultural context of biological adaptation to high elevation Tibet

“…In humans, chronic hypoxia has been linked to individual manifestations of heart disease, stroke, anemia, pulmonary hyptertension, low birthweight and infant mortality that carry population-level consequences (excellent recent reviews include : Beall, 2013;Bigham and Lee, 2014;Scheinfeldt and Tishkoff, 2013;Simonson, 2015). As with other organisms (see Storz et al, 2010Storz et al, , 2013, several human populations have developed geographically distinct, and genetically-based pulmonary, hematological and/or vascular adaptations to low-oxygen environments (Beall, 2007;Hornbein and Schoene, 2001;Scheinfeldt and Tishkoff, 2013;Simonson et al, 2012).…”

“…In humans, chronic hypoxia has been linked to individual manifestations of heart disease, stroke, anemia, pulmonary hyptertension, low birthweight and infant mortality that carry population-level consequences (excellent recent reviews include : Beall, 2013;Bigham and Lee, 2014;Scheinfeldt and Tishkoff, 2013;Simonson, 2015). As with other organisms (see Storz et al, 2010Storz et al, , 2013, several human populations have developed geographically distinct, and genetically-based pulmonary, hematological and/or vascular adaptations to low-oxygen environments (Beall, 2007;Hornbein and Schoene, 2001;Scheinfeldt and Tishkoff, 2013;Simonson et al, 2012). Genome-wide analyses of contemporary Tibetan populations, for example, suggest that the genetic foundations for at least some of these adaptations were under strong directional selection, a likely testament to the fitness benefits associated with them (Beall et al, 2004(Beall et al, , 2010Bigham et al, 2010;Peng et al, 2011;Simonson et al, 2010;Wang et al, 2011;Xu et al, 2011;Yi et al, 2010).…”