Gene Flow and Natural Selection in Oceanic Human Populations, Inferred from Genome-wide SNP Typing (H/T
Dienekes):
It is suggested that the major prehistoric human colonizations of Oceania occurred twice, namely, about 50,000 and 4,000 years ago. The first settlers are considered as ancestors of indigenous people in New Guinea and Australia. The second settlers are Austronesian-speaking people who dispersed by voyaging in the Pacific Ocean. In this study, we performed genome-wide SNP typing on an indigenous Melanesian (Papuan) population, Gidra, and a Polynesian population, Tongans, by using the Affymetrix 500K assay. The SNP data were analyzed together with the data of the HapMap samples provided by Affymetrix. In agreement with previous studies, our phylogenetic analysis indicated that indigenous Melanesians are genetically closer to Asians than to Africans and European Americans. Population structure analyses revealed that the Tongan population is genetically originated from Asians at 70% and indigenous Melanesians at 30%, which thus supports the so-called "Slow train" model. We also applied the SNP data to genome-wide scans for positive selection by examining haplotypic variation, and identified many candidates of locally selected genes. Providing a clue to understand human adaptation to environments, our approach based on evolutionary genetics must contribute to revealing unknown gene functions as well as functional differences between alleles. Conversely, this approach can also shed some light onto the invisible phenotypic differences between populations.
The stuff about candidates for selection:
Our scans suggested no private mutation to exist on the Tongan autosomes that had reached fixation. However, there remain alternative possibilities that old-standing alleles have reached fixation by local selective pressures and that newly generated advantageous mutations have gained a high frequency but have not yet reached fixation. The block showing the lowest RM value (0.076) in the test of TGN vs EAS using method 1 was located at 92788024-92838919 on chromosome 12...which is at 41 kb distance from the CRADD gene...It is worth noting that an approximately 500 kb deletion around this gene in mouse has been reported to cause a high growth mutant that shows a proportional increase in tissue and organ size without obesity...Another candidate for the selected region in which an old-standing allele reached fixation was VLDLR...which is involved in triglyceride and fatty acid metabolism...In addition, overlapping signatures in both methods 1 and 2...were observed in the gene region of EXT2, which is a causal gene of the type II form of multiple exostoses and it plays a crucial role in bone formation...These genes can be candidates that are associated with the large fat, muscle, and bone masses of Polynesians. A recent paper examining the interpopulation differentiation of the type II diabetes-associated genes has suggested that a susceptible allele of PPARGC1A may play a role in the large difference in the prevalence of the disease between Polynesians and neighboring populations...However, our scans did not identify any signiture of positive selection on the gene region of PPARGC1A.
One of the strongest signatures of selective sweeps in GDP was located at the region 22 including the LHX4 and ACBD6 genes on chromosome 1...LHX4 encodes a transcriptional regulator involved in the control of the development of the pituitary gland, and mutations in this gene are associated with syndromic short stature and pituitary defects...ACBD6 is a binding protein of acyl-Coenzyme A that has a role in fatty acid metabolism...The gene region of IGF1R, which is the receptor for insulin-like growth factor 1...was also considered to be a candidate of the selected genes...These genes may be involved in the slow growth, short stature, and light weight characteristics of New Guineans. Future association studies between genotypes and phenotypes are indispensable.
Other candidates of selective sweeps in Oceanic populations included several interesting genes such as DDX58, SIAT4A...and IVNS1ABP...which code molecules related with infection of the influenza A viruses...If we could identify a protective effect of the selected allele against the influenza, these kinds of signatures may therefore suggest evidence for the epidemic history of the virus in Oceania and human conquest of the disease by genetic adaptation.
Labels: Population genetics
