March 07, 2006

Recent positive selection in humans

Yet another study on positive selection in modern humans; you can find many many more by searching for "recent selection" or "positive selection" via the site search on the right sidebar.

The findings are reported in PLoS Biology (free text). Nicholas Wade also covers the study in the New York Times:
Providing the strongest evidence yet that humans are still evolving, researchers have detected some 700 regions of the human genome where genes appear to have been reshaped by natural selection, a principal force of evolution, within the last 5,000 to 15,000 years.

The genes that show this evolutionary change include some responsible for the senses of taste and smell, digestion, bone structure, skin color and brain function.

Many of these instances of selection may reflect the pressures that came to bear as people abandoned their hunting and gathering way of life for settlement and agriculture, a transition well under way in Europe and East Asia some 5,000 years ago.
From the new paper:
A fully rigorous estimation of the ages of the candidate sweeps is difficult with the current data. However, making the simplistic assumption of a star-shaped genealogy for the favored haplotypes and assuming a generation time of 25 y, suggests average ages of ≍6,600 years and ≍10,800 years in the non-African, and African populations, respectively (Materials and Methods).


Some of the strongest signals of recent selection appear in various types of genes related to morphology. For example, four genes involved in skin pigmentation show clear evidence of selection in Europeans (OCA2, MYO5A, DTNBP1, TYRP1). All four genes are associated with Mendelian disorders that cause lighter pigmentation or albinism, and all are in different genomic locations, indicating the action of separate selective events. One of these genes, OCA2, is associated with the third longest haplotype on a high frequency SNP anywhere in the genome for Europeans. A fifth gene, SLC24A5, has recently been shown by another group to impact skin pigmentation and to have a derived, selected allele near fixation in Europeans [45]. Though iHS has reduced power for alleles near fixation, SNPs near this gene also show strong iHS signals in Europeans (Table S2).

Various genes involved in skeletal development have also been targets of recent selection. Three related proteins involved in bone morphogenesis show signals of selection in Europeans (BMP3 and BMPR2) and in East Asians (BMP5). In addition, GDF5, a gene in which mutations cause skeletal malformations, shows strong signals of selection in both Europeans and East Asians. Other morphological features also appear to be targets of selection, including hair formation and patterning in Yoruba (the keratin cluster near 17q12; and FZD6).

An important type of selective pressure that has confronted modern humans is the transition to novel food sources with the advent of agriculture and the colonization of new habitats [19,21]. As noted above, we see a strong signal of selection in the alcohol dehydrogenase (ADH) cluster in East Asians, including the third longest haplotype around a high frequency allele in East Asians. A variety of genes involved in carbohydrate metabolism have evidence for recent selection, including genes involved in metabolizing mannose (MAN2A1 in Yoruba and East Asians), sucrose (SI in East Asians), and lactose (LCT in Europeans). Processing of dietary fatty acids is another system with signals of strong selection, including uptake (SLC27A4 and PPARD in Europeans), oxidation (SLC25A20 in East Asians) and regulation (NCOA1 in Yoruba and LEPR in East Asians). The latter gene (LEPR) is the leptin receptor and plays an important role in regulating adipose tissue mass.

Recent articles have proposed that genes involved in brain development and function may have been important targets of selection in recent human evolution [8,9]. While we do not find evidence for selection in the two genes reported in those studies (MCPH1 and ASPM), we do find signals in two other microcephaly genes, namely, CDK5RAP2 in Yoruba, and CENPJ in Europeans and East Asians [46]. Though there is not an overall enrichment for neurological genes in our gene ontology analysis, several other important brain genes also have signals of selection, including the primary inhibitory neurotransmitter GABRA4, an Alzheimer's susceptibility gene PSEN1, and SYT1 in Yoruba; the serotonin transporter SLC6A4 in Europeans and East Asians; and the dystrophin binding gene SNTG1 in all populations.

PLoS Biology Volume 4 | Issue 3 | MARCH 2006

A Map of Recent Positive Selection in the Human Genome

Benjamin F. Voight1, Sridhar Kudaravalli1, Xiaoquan Wen1, Jonathan K. Pritchard1*

The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP) data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest ∼250 signals of recent selection in each population.


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