Gene Evolution and Human Adaptation


Regions of the human genome that have been subject to past positive selection contain patterns of genetic variation that are markedly different in specific ways from regions that have not experienced positive selection. By uncovering these so‐called signatures of positive selection in the genome we can discover the unique ways in which humans have evolved. Genome‐wide scans have revealed signatures of positive selection on the human lineage since we diverged from chimpanzees, as well as signatures of positive selection specific to regional human populations. New research has found that much of human population adaptation may have occurred by positive selection causing modest increases in frequency of beneficial variants at multiple loci that all result in the shift of the expression of a feature (like height) in a particular direction.

Key Concepts:

  • Hundreds of genes have been found that bear signatures of positive selection on the human lineage with genes mainly falling into categories of chemoreception, immune defence, reproduction and fertilisation as well as apoptosis.

  • Most studies of positive selection have focused their work on the protein‐coding portion of the genome, yet many sites of positive selection may fall in noncoding regions where new research is detecting many functional elements.

  • There is much active research trying to identify the extent to which DNA substitutions in regulatory elements underlay our adaptations.

  • Much needed in future research is experimental work that aims to pinpoint causal variants within genomes and the phenotypic effects of genomic regions showing signatures of positive selection.

  • The traditional signature of selection, a ‘classic selective sweep’, appears to be rare in large resequencing datasets of diverse world populations leading researchers to begin searching for signatures of ‘soft selective sweeps’ where weak positive selection acts to subtly increase the frequency of DNA variants at multiple loci with all variants contributing to a shift in a phenotype's expression in the same direction.

Keywords: adaptation; positive selection; human evolution; comparative genomics; population genetics; selective sweep; human variation

Figure 1.

From bottom to top, this illustration shows the evolutionary divergence of chimpanzees and humans from their common ancestor. More recently along the human lineage is represented the origin of Homo sapiens and its subsequent differentiation into different regional populations (Time‐scales along the lineages leading to humans and chimpanzees have been compressed). Human species‐wide adaptations have evolved along the human lineage from the initial time of divergence (∼6–7 million years ago) up until the time of the differentiation of H. sapiens populations. On the other hand, population‐level adaptations have evolved as human populations differentiated and adapted to different geographic regions. On the right, we show five signatures in the patterns of DNA variation that can indicate that a DNA region has experienced positive selection. These are arranged according to the time frame in human evolution in which they can reveal the process of positive selection.

Figure 2.

Proceeding from left to right, the figure illustrates the evolutionary process known as a selective sweep (also called a ‘classic’ or ‘hard’ sweep). Each of the seven DNA sequences represents a copy of DNA carried by an individual in a population. In the left hand panel, the seven DNA copies show a pattern of variants (coloured in blue) that might be expected under neutrality, some variants are present only in a single individual in the sample (i.e. are rare variants) and some are present in more individuals (i.e. are at higher frequencies). The third sequence from the top has recently acquired an advantageous mutation C (coloured in red and denoted by a star). Under positive selection, this DNA copy will be driven to higher and higher frequencies in the population whereas all other copies become lost, so that in the middle panel, all DNA copies drawn from the population possess the advantageous mutation. According to the process known as ‘hitchhiking’, the neutral variants G, A and T (shaded) linked to the beneficial variant are also spread to all individuals in the populations. The selective sweep has also ‘swept’ away (or removed) all other variants originally present in the population, resulting in a decrease in genetic diversity in the population in the region of DNA near the advantageous mutation. The panel on the right represents DNA copies drawn from the population just after the sweep while the population is in recovery‐phase. The mutation process has introduced new variants to the population (coloured in blue). Since the population has not reached equilibrium, all new variants still exist at low frequencies (i.e. they are rare variants).

Figure 3.

A ‘classic selective sweep’ (left) compared with a polygenic ‘soft sweep’ (right). In a classic selective sweep, the beneficial DNA variant (indicated by a red star) arises de novo in the population and immediately spreads relatively rapidly through the population to become near or at 100% frequency. Since all neutral variants linked to the beneficial variant also rise in frequency along with the beneficial variant there is a region (denoted in blue) that surrounds the variant in which all chromosomes are identical by descent (this is also the signature called a long haplotype) and exhibit low variation. In the ‘soft sweep’, adaptation occurs at multiple loci (5 loci in this example), so‐called polygenetic adaptation. At all loci, slight shifts of beneficial variants to higher frequencies cause a phenotype (such as height) to shift in the same direction. At loci numbers 1, 2 and 4, positive selection acts on DNA variants already present at low or modest frequencies in the population (i.e. standing variation) and brings these variants to slightly higher frequencies but does not produce signatures of a ‘classic sweep’ because the fitness effects of each individual locus is relatively small compared with the fitness effects of a locus in a classic sweep. At loci 3 and 5, the beneficial variants arose de novo and increased to slightly higher frequencies. Since they are new variants that quickly spread within the population, they create signatures of partial sweeps, meaning slightly reduced levels of variation in regions surrounding the beneficial variant as well as regions identical by descent on the chromosomes bearing the beneficial variant. Adapted with permission from Pritchard et al., copyright by Elsevier.



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Harris, Eugene E(Jan 2013) Gene Evolution and Human Adaptation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020773.pub2]