Spatial patterns of variation due to natural selection in humans Export

@article{citeulike:5971537, abstract = {Empowered by technology and sampling efforts designed to facilitate genome-wide association mapping, human geneticists are now studying the geography of genetic variation in unprecedented detail. With high genomic coverage and geographic resolution, these studies are identifying loci with spatial signatures of selection, such as extreme levels of differentiation and correlations with environmental variables. Collectively, patterns at these loci are beginning to provide new insights into the process of human adaptation. Here, we review the challenges of these studies and emerging results, including how human population structure has influenced the response to novel selective pressures.}, author = {Novembre, John and Di Rienzo, Anna}, citeulike-article-id = {5971537}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nrg2632}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nrg2632}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19823195}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19823195}, comment = {1. Marked geographic patterns for the distribution of some heritable traits are observed in humans, including traits related to disease risk, pathogen resistance and drug response. In some cases, the geographic patterns may be due to natural selection, as shown by correlations between traits and environmental variables (for example, correlations between skin pigmentation and latitude). 2. Spatial patterns of adaptive genetic variation are informative about selective processes. For example, during the spread of an advantageous allele, one can transiently observe 'wave of advance' patterns, or if spatial selection pressures vary across space, stable correlations of allele frequency with environmental variables may be generated. 3. Spatial patterns of neutral variation are also influenced by demographic history. Because some of these genome-wide features may resemble signals of selection, it is important to incorporate information on background spatial patterns of variation when assessing the evidence for adaptations. 4. The extent of allele frequency differentiation across populations can be summarized by the FST statistic. The excess of highly differentiated alleles seen in humans has been interpreted as an effect of positive selection driving diversification between populations. 5. High FST values may also be due to background selection. Because background selection is likely to act more strongly in genic then in non-genic regions, negative rather than positive selection could account for part or all of the observed excess of high FST for genic relative to non-genic SNPs. 6. If selection is strong, targets of local adaptations are expected to have extreme levels of differentiation relative to neutral loci. Accordingly, several variants that confer locally advantageous phenotypes exhibit unusually high levels of allele frequency differences across populations. 7. In natural populations of many species, several quantitative traits are distributed clinally, which mirrors the selective pressures acting on the phenotypes. This observation is consistent with the idea that adaptive genetic variants are also correlated with geographic or environmental variables. 8. Clines of allele frequencies with latitude have been observed for several hypertension susceptibility variants. Moreover, polymorphisms in candidate genes for metabolic syndrome were found to be correlated with climate variables, which is consistent with the hypothesis that spatial patterns of variation are influenced by selective pressures related to thermal stress. 7. Spatial population structure seems to limit the spread of advantageous alleles in humans. Therefore novel mutations and/or standing variation may be more important sources of adaptive variation at a continental scale than the arrival of adaptive alleles through dispersal}, day = {13}, doi = {10.1038/nrg2632}, issn = {1471-0056}, journal = {Nat Rev Genet}, keywords = {genetics, geography, natural\_selection, population, population\_genetics, population\_structure}, month = {October}, number = {11}, pages = {745--755}, posted-at = {2009-11-05 12:55:24}, priority = {2}, publisher = {Nature Publishing Group}, title = {Spatial patterns of variation due to natural selection in humans}, url = {http://dx.doi.org/10.1038/nrg2632}, volume = {10}, year = {2009} }

TY - JOUR ID - citeulike:5971537 L3 - citeulike-article-id:5971537 N2 - Empowered by technology and sampling efforts designed to facilitate genome-wide association mapping, human geneticists are now studying the geography of genetic variation in unprecedented detail. With high genomic coverage and geographic resolution, these studies are identifying loci with spatial signatures of selection, such as extreme levels of differentiation and correlations with environmental variables. Collectively, patterns at these loci are beginning to provide new insights into the process of human adaptation. Here, we review the challenges of these studies and emerging results, including how human population structure has influenced the response to novel selective pressures. IS - 11 JF - Nat Rev Genet SN - 1471-0056 EP - 755 TI - Spatial patterns of variation due to natural selection in humans PB - Nature Publishing Group VL - 10 SP - 745 KW - genetics KW - geography KW - natural_selection KW - population KW - population_genetics KW - population_structure N1 - 1. Marked geographic patterns for the distribution of some heritable traits are observed in humans, including traits related to disease risk, pathogen resistance and drug response. In some cases, the geographic patterns may be due to natural selection, as shown by correlations between traits and environmental variables (for example, correlations between skin pigmentation and latitude). 2. Spatial patterns of adaptive genetic variation are informative about selective processes. For example, during the spread of an advantageous allele, one can transiently observe 'wave of advance' patterns, or if spatial selection pressures vary across space, stable correlations of allele frequency with environmental variables may be generated. 3. Spatial patterns of neutral variation are also influenced by demographic history. Because some of these genome-wide features may resemble signals of selection, it is important to incorporate information on background spatial patterns of variation when assessing the evidence for adaptations. 4. The extent of allele frequency differentiation across populations can be summarized by the FST statistic. The excess of highly differentiated alleles seen in humans has been interpreted as an effect of positive selection driving diversification between populations. 5. High FST values may also be due to background selection. Because background selection is likely to act more strongly in genic then in non-genic regions, negative rather than positive selection could account for part or all of the observed excess of high FST for genic relative to non-genic SNPs. 6. If selection is strong, targets of local adaptations are expected to have extreme levels of differentiation relative to neutral loci. Accordingly, several variants that confer locally advantageous phenotypes exhibit unusually high levels of allele frequency differences across populations. 7. In natural populations of many species, several quantitative traits are distributed clinally, which mirrors the selective pressures acting on the phenotypes. This observation is consistent with the idea that adaptive genetic variants are also correlated with geographic or environmental variables. 8. Clines of allele frequencies with latitude have been observed for several hypertension susceptibility variants. Moreover, polymorphisms in candidate genes for metabolic syndrome were found to be correlated with climate variables, which is consistent with the hypothesis that spatial patterns of variation are influenced by selective pressures related to thermal stress. 7. Spatial population structure seems to limit the spread of advantageous alleles in humans. Therefore novel mutations and/or standing variation may be more important sources of adaptive variation at a continental scale than the arrival of adaptive alleles through dispersal AU - Novembre, John AU - Di Rienzo, Anna PY - 2009/10/13/ UR - http://dx.doi.org/10.1038/nrg2632 ER -