Identifying Regions of the Human Genome that Exhibit Evidence of Positive Selection


The recent availability of genomic data from humans has driven genome‐wide scans for natural selection; these scans use several approaches based on comparative genetics and population genetics. Such studies have identified many possible occurrences of positive selection in the human genome, but the results should be interpreted with caution because false positives are unavoidable. Here, we review approaches for identifying positive selection in the human genome, and explain in detail an approach designed to detect recent positive selection; this approach is based on haplotype variation and linkage disequilibrium. Signatures of positive selection in the human genome offer clues on how biological features of humans have evolved and on how humans have genetically adapted to their environments and own lifestyles – including climate, diet and pathogens.

Key Concepts:

  • Comparative genetics approaches identify human‐specific constraint or accelerated gene evolution, but have a methodological limitation.

  • Population genetics approaches based on haplotype variation effectively detect recent positive selection.

  • Genome‐wide scans for selection have identified a number of candidate loci; these findings enable us to reconstruct the history of human genetic adaptation.

  • The results of scans for selection have to be interpreted with caution since the occurrence of false positives and false negatives is inevitable.

  • Further improvements in statistical analysis and establishment of functional analysis are required for future studies to validate variants associated with adaptive phenotypes.

Keywords: natural selection; genetic adaptation; human genome; genetic diversity; selective sweep; haplotype variation; phenotypic difference; selective pressure

Figure 1.

Approaches for detecting natural selection and the relevant time scales.

Figure 2.

Conservation of the haplotype harbouring a beneficial mutation.

Figure 3.

Scheme for determining Extended Haplotype Homozygosity (EHH). (a) Extended haplotypes. Dark and light grey boxes represent different alleles. Extended haplotypes are determined for each distance from the core SNP. (b) The decay of EHH. Relative EHH can be calculated at any arbitrary distance. X1, 100 kb of physical distance; X2, the point just before EHH for the test allele drops below 0.4 and X3, the point just after EHH for the test allele drops below 0.05. EHH can be integrated (iHH).

Figure 4.

The patterns of EHHR/EHHT values around a selected locus. (a) The results from simulations under neutrality. (b) The results from simulations modelling various frequencies (p) of the selected allele (2Nes=300). EHHR/EHHT values (y axis) of SNPs within 200 kb around the selected loci were counted for each bin of the allele frequency (x axis). Data from 500 replications were put together and counted.

Figure 5.

Definition of blocks that cover a region under a complete selective sweep in a population: (a) HH1≥0.5, (b) HH1≥0.9.



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Further Reading

Biswas S and Akey JM (2006) Genomic insights into positive selection. Trends in Genetics 22: 437–446.

Nielsen R , Hellmann I , Hubisz M , Bustamante C and Clark AG (2007) Recent and ongoing selection in the human genome Nature Reviews Genetics 8: 857–868.

Sabeti PC , Schaffner SF , Fry B et al. (2006) Positive natural selection in the human lineage. Science 312: 1614–1620.

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Kimura, Ryosuke, and Ohashi, Jun(Nov 2013) Identifying Regions of the Human Genome that Exhibit Evidence of Positive Selection. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020850.pub2]