PMC:3492649 / 7975-11995 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3492649","sourcedb":"PMC","sourceid":"3492649","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3492649","text":"Local Adaptation of Admixed Populations\nIdentifying targets of positive selection in humans has been a central topic in human evolutionary and population genetics. Traditional studies have been relying on the analysis of individual candidate genes. Since the genomics era, the availability of high-density SNPs has provided essential resources for systematically interrogating the entire genome for detecting signatures of natural selection. As a matter of fact, many genomewide scans for recent or ongoing positive selection have been recently performed in humans, while most of the studies to date have been performed in non-admixed populations. In the situation of genetic admixture, when previously isolated populations meet and mix, the resulting admixed population can benefit from several genetic advantages, including increased genetic variation, the creation of novel genotypes, and the masking of deleterious mutations, and these admixture benefits are thought to play an important role in biological adaptation to local environment. As a result, this has led to the use of admixture estimates to detect the action of natural selection in human populations. Such techniques have been regarded as powerful methods for the detection of selection effects, especially when an appreciable number of generations have elapsed since the original admixture.\nSeveral studies based on genomic data have been conducted in recently admixed populations in the New World [42-44]. Recently, we developed a new approach that can be used to detect natural selection both before and after population admixture, and we applied this method in AfA data. It is particularly meaningful to investigate natural selection in AfAs due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal SNPs genotyped in 5,210 individuals and conducted a genomewide search for selection signals in 1,890 AfAs. Several genomic regions showing excess African or EUR ancestry, which were thought of as the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre- and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfAs and comparing it with indigenous African populations (IAF). Interestingly, many selection candidate genes identified by the new approach were associated with AfA-specific high-risk diseases, such as prostate cancer and hypertension, suggesting an important role that these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than that in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the 2 approaches, indicating the different environmental pressures AfAs experienced pre- and post-population admixture. We suggest that the new approach (see Fig. 2 for a schematic framework of this approach) is reasonably powerful and can also be applied to other admixed populations, such as Latinos and Uyghurs.\nI will not go further on this topic in this review paper, since so far there is no study that has been performed in Asian populations using admixture analysis. However, we believe that the discoveries have greatly enriched our understanding of human origins and history and hold large potential for identifying genes with important biological functions; this, in turn, will elucidate the genetic basis of some human diseases [45, 46]. These studies together provide many new insights into the natural selection process and mechanisms, which will ultimately improve the modern evolution theory.","divisions":[{"label":"Title","span":{"begin":0,"end":39}}],"tracks":[{"project":"2_test","denotations":[{"id":"23166524-17701908-44844040","span":{"begin":1467,"end":1469},"obj":"17701908"},{"id":"23166524-18752003-44844040","span":{"begin":1467,"end":1469},"obj":"18752003"},{"id":"23166524-20080753-44844040","span":{"begin":1467,"end":1469},"obj":"20080753"},{"id":"23166524-17943131-44844041","span":{"begin":3853,"end":3855},"obj":"17943131"},{"id":"23166524-19411596-44844042","span":{"begin":3857,"end":3859},"obj":"19411596"}],"attributes":[{"subj":"23166524-17701908-44844040","pred":"source","obj":"2_test"},{"subj":"23166524-18752003-44844040","pred":"source","obj":"2_test"},{"subj":"23166524-20080753-44844040","pred":"source","obj":"2_test"},{"subj":"23166524-17943131-44844041","pred":"source","obj":"2_test"},{"subj":"23166524-19411596-44844042","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93eccd","default":true}]}]}}