Differences in allele frequency

Marked differences in allele frequency between populations can also provide evidence that a locus has been subject to selection, with differing selection pressures between the populations (Weir and Cockerham 1984). This has been highly informative for recent events, notably with genes subject to selection by malaria with the allele frequency of particular variants of the HBB gene (such as Hb S) and DARC (Duffy blood group, chemokine receptor) gene geographically strongly related to malarial endemicity (discussed further in Section 13.2). The utility of the approach requires some degree of reproductive isolation between populations and is therefore more informative for human populations after the proposed migration of modern humans out of Africa over the last 75 000 years (Box 8.5).

Approaches analysing long haplotypes present at high frequency

• Only useful for recent events over last 30 000 years

• Example shown for common long haplotype associated with lactase persistence in Europeans

Analysis based on population differences in allele frequency

• Requires a degree of reproductive isolation between populations and most informative over last 75 000 years.

• Example shown for variation in allele frequency of FY*O allele associated with protection from malaria (Section 13.2.4)

Defining loci with high frequency derived alleles

• Comparison betwen species allowing ancestral and derived alleles to be inferred

• Genetic hitch-hiking means a region containing a favourable allele may contain a high frequency of linked derived alleles carried to near fixation

Analysis of regions of low diversity (heterozygosity) with excess of rare alleles

• Selective sweep with fixation of favourable allele and linked variants leading to loss of diversity (heterozygosity); over time new mutations mean an excess of rare alleles in a region of low diversity may be seen



Europe t

75 000 years ago t t

6 000 000 250 000 years ago years ago t

75 000 years ago


Asia t

25 000 years ago


Analysis of 'functional' variants such as nonsynonymous versus synonymous

• Between and within species

• Define increased rate of fixation for nonsynonymous vs synonymous changes at a locus

• Examples include PRM! gene, encoding protamine 1, involved in spermatogenesis

Figure 10.1 Finding evidence of positive selection using different approaches. Figures and text adapted from Sabeti et al. (2006), reprinted with permission from AAAS.

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