Positive Natural Selection in the Human Lineage

Abstract

Positive natural selection is the force that drives the increase in prevalence of advantageous traits, and it has played a central role in our development as a species. Until recently, the study of natural selection in humans has largely been restricted to comparing individual candidate genes to theoretical expectations. The advent of genome-wide sequence and polymorphism data brings fundamental new tools to the study of natural selection. It is now possible to identify new candidates for selection and to reevaluate previous claims by comparison with empirical distributions of DNA sequence variation across the human genome and among populations. The flood of data and analytical methods, however, raises many new challenges. Here, we review approaches to detect positive natural selection, describe results from recent analyses of genome-wide data, and discuss the prospects and challenges ahead as we expand our understanding of the role of natural selection in shaping the human genome.

An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) gene

“…This is particularly true for the Val di Scalve sample, for which the presence of a single predominant haplotype and the results of neutrality tests suggest the occurrence of a founder effect followed by strong genetic Looking back to the evolutionary history of such a young and cosmopolitan species as H. sapiens, it is coherent to believe that our pathogens, which live in the extremely diversified environments colonized by modern humans, may have represented one of the major selective pressures on our genome. Thereby, genes whose function is strictly related to the immune system are supposed to be more likely subjected to the action of natural selection respect to other typology of genes, as recently confirmed by Sabeti et al 38 In particular, genes involved in adaptive immunity, such as TNFRSF13B, are likely to be subjected to recent geographically localized selective pressures, as they may interact with local pathogen landscapes, resulting in increased interpopulations genetic differentiation. We therefore sought for genetic footprints of selection at the TNFRSF13B gene by means of several neutrality tests based on the frequency spectrum of mutations (Tajima's D, Fu and Li's D, F and Fay and Wu's H) and on the comparison of human intraspecific genetic diversity and human/chimpanzee interspecific divergence (McDonald-Kreitman and HKA tests).…”

Signatures of strong population differentiation shape extended haplotypes across the human CD28 , CTLA4 , and ICOS costimulatory genes

“…One could envision continuous selective pressure in Afri- can populations leading to the predominance of haplotypes ICOSp.h5, ICOSp.h6, and ICOSp.h7 (Ͼ60%), all bearing ICOSp.2C, whereas the migration out of Africa favored a gradual rise in frequency of ICOSp.h4 and the derived haplotypes ICOSp.h1 and ICOSp.h8. Because these events are expected to have happened over the last 60,000-80,000 years, selective signatures such as EHH over long stretches would be more modest than the selective signature of malaria or cattle domestication, both of which are more recent (12,23,24,32).…”

“…In the case of a bottlenecked population, the overall diversity is expected to be reduced, with a few haplotypes accounting for the bulk of the chromosomes. Recent positive selection (20,000 years or less), differentially affecting population groups, is characterized by a pattern of high-frequency haplotypes maintaining long neighboring segments in strong LD (23). To explore the costimulatory locus for such signatures, we analyzed the LD patterns using extended haplotype homozygosity (EHH) statistics, which focus on the relationship between the frequency of a given core haplotype and the span of SNP homozygosity at increasing distances from that core (24).…”

Evolutionary genetics of affective disorders

“…The primary models based on effects of positive selection (selection 'for' particular genetic variants, that arise and sweep through populations to some frequency; Sabeti et al 2006;Hughes 2007) that have been proposed include: (1) changing selection pressures, such that common alleles that were advantageous in ancestral environments (for example, 'thrifty' genes affecting the regulation of metabolism) are now deleterious, and derived alleles are selected for (Di Rienzo and Hudson 2005;Di Rienzo 2006), (2) balancing selection, whereby individuals with heterozygous genotypes are favored, resulting in the maintenance at high frequency of deleterious homozygotes, and (3) antagonistic pleiotropy, whereby selected alleles exert positive effects in one context, or early in the lifespan, that are stronger than, or balanced by, negative effects expressed in some other context or later in life (Keller and Miller 2006;Kryukov et al 2007). …”

“…Thus, just as a phenotype may be adaptive or maladaptive in some environmental context, an allele or haplotype may have increased or decreased in frequency as a result of selection over evolutionary time, or it may be maintained at some intermediate frequency. For evolutionary analyses of mental disorders, a focus at the level of alleles and haplotypes offers a number of useful analytic properties, such as the ability to infer the action of population-genetic processes, including selection for advantageous alleles, selection against deleterious alleles, or genetic drift, from data collected in extant populations (e. g., Biswas and Akey 2006; Sabeti et al 2006;Boyko et al 2008). Such evolutionary-genetic analyses permit rigorous quantification of how natural selection, drift, mutation, and other processes have influenced genetic liability to affective disorders, which in turn provides direct insights into the proximate genetic, physiological and developmental underpinnings of mental disorders, and the role of optimization by selection in ultimate-level studies of adaptive significance (Crespi et al 2007).…”