Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans.

The human DARC (Duffy antigen receptor for chemokines) gene encodes a membrane-bound chemokine receptor crucial for the infection of red blood cells by Plasmodium vivax, a major causative agent of malaria. Of the three major allelic classes segregating in human populations, the FY*O allele has been shown to protect against P. vivax infection and is at near fixation in sub-Saharan Africa, while FY*B and FY*A are common in Europe and Asia, respectively. Due to the combination of strong geographic differentiation and association with malaria resistance, DARC is considered a canonical example of positive selection in humans. Despite this, details of the timing and mode of selection at DARC remain poorly understood. Here, we use sequencing data from over 1,000 individuals in twenty-one human populations, as well as ancient human genomes, to perform a fine-scale investigation of the evolutionary history of DARC. We estimate the time to most recent common ancestor (TMRCA) of the most common FY*O haplotype to be 42 kya (95% CI: 34-49 kya). We infer the FY*O null mutation swept to fixation in Africa from standing variation with very low initial frequency (0.1%) and a selection coefficient of 0.043 (95% CI:0.011-0.18), which is among the strongest estimated in the human genome. We estimate the TMRCA of the FY*A mutation in non-Africans to be 57 kya (95% CI: 48-65 kya) and infer that, prior to the sweep of FY*O, all three alleles were segregating in Africa, as highly diverged populations from Asia and ≠Khomani San hunter-gatherers share the same FY*A haplotypes. We test multiple models of admixture that may account for this observation and reject recent Asian or European admixture as the cause

Comparison of village dog and wolf genomes highlights the role of the neural crest in dog domestication

Abstract Background Domesticated from gray wolves between 10 and 40 kya in Eurasia, dogs display a vast array of phenotypes that differ from their ancestors, yet mirror other domesticated animal species, a phenomenon known as the domestication syndrome. Here, we use signatures persisting in dog genomes to identify genes and pathways possibly altered by the selective pressures of domestication. Results Whole-genome SNP analyses of 43 globally distributed village dogs and 10 wolves differentiated signatures resulting from domestication rather than breed formation. We identified 246 candidate domestication regions containing 10.8 Mb of genome sequence and 429 genes. The regions share haplotypes with ancient dogs, suggesting that the detected signals are not the result of recent selection. Gene enrichments highlight numerous genes linked to neural crest and central nervous system development as well as neurological function. Read depth analysis suggests that copy number variation played a minor role in dog domestication. Conclusions Our results identify genes that act early in embryogenesis and can confer phenotypes distinguishing domesticated dogs from wolves, such as tameness, smaller jaws, floppy ears, and diminished craniofacial development as the targets of selection during domestication. These differences reflect the phenotypes of the domestication syndrome, which can be explained by alterations in the migration or activity of neural crest cells during development. We propose that initial selection during early dog domestication was for behavior, a trait influenced by genes which act in the neural crest, which secondarily gave rise to the phenotypes of modern dogs

Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans

<div><p>The human DARC (Duffy antigen receptor for chemokines) gene encodes a membrane-bound chemokine receptor crucial for the infection of red blood cells by <i>Plasmodium vivax</i>, a major causative agent of malaria. Of the three major allelic classes segregating in human populations, the FY*O allele has been shown to protect against <i>P. vivax</i> infection and is at near fixation in sub-Saharan Africa, while FY*B and FY*A are common in Europe and Asia, respectively. Due to the combination of strong geographic differentiation and association with malaria resistance, DARC is considered a canonical example of positive selection in humans. Despite this, details of the timing and mode of selection at DARC remain poorly understood. Here, we use sequencing data from over 1,000 individuals in twenty-one human populations, as well as ancient human genomes, to perform a fine-scale investigation of the evolutionary history of DARC. We estimate the time to most recent common ancestor (T</p><p>_MRCA</p>) of the most common FY*O haplotype to be 42 kya (95% CI: 34–49 kya). We infer the FY*O null mutation swept to fixation in Africa from standing variation with very low initial frequency (0.1%) and a selection coefficient of 0.043 (95% CI:0.011–0.18), which is among the strongest estimated in the human genome. We estimate the T<p>_MRCA</p> of the FY*A mutation in non-Africans to be 57 kya (95% CI: 48–65 kya) and infer that, prior to the sweep of FY*O, all three alleles were segregating in Africa, as highly diverged populations from Asia and ≠Khomani San hunter-gatherers share the same FY*A haplotypes. We test multiple models of admixture that may account for this observation and reject recent Asian or European admixture as the cause.<p></p></div

FY*O selection coefficient results.

<p>Prior and posterior distributions of FY*O selection coefficient.</p

Geographical distribution of allelic classes in samples.

<p>*The FY*O/FY*A haplotype is a very rare haplotype that includes both the FY*A and FY*O mutations and is present only in the Zulu samples.</p

Haplotype networks.

<p>Median joining networks of three subsets of haplotypes in the 5kb region centered on the FY*O mutation. The FY*A mutation is located 671 bps downstream from the FY*O mutation. Arrows indicates ancestral sequence. A) All haplotypes observed at least four times B) All FY*O haplotypes observed at least twice. (Note that none of the FY*O haplotypes in this network also carry the FY*A mutation.) C) All FY*A haplotypes observed at least twice. (Note that none of the FY*A hapotypes in this network also include the FY*O mutation.)</p

Selection scan results.

<p>Selection scan results.</p