Genome-wide landscapes of human local adaptation in Asia

Abstract

Genetic studies of human local adaptation have been facilitated greatly by recent advances in high-throughput genotyping and sequencing technologies. However, few studies have investigated local adaptation in Asian populations on a genome-wide scale and with a high geographic resolution. In this study, taking advantage of the dense population coverage in Southeast Asia, which is the part of the world least studied in term of natural selection, we depicted genome-wide landscapes of local adaptations in 63 Asian populations representing the majority of linguistic and ethnic groups in Asia. Using genome-wide data analysis, we discovered many genes showing signs of local adaptation or natural selection. Notable examples, such as FOXQ1, MAST2, and CDH4, were found to play a role in hair follicle development and human cancer, signal transduction, and tumor repression, respectively. These showed strong indications of natural selection in Philippine Negritos, a group of aboriginal hunter-gatherers living in the Philippines. MTTP, which has associations with metabolic syndrome, body mass index, and insulin regulation, showed a strong signature of selection in Southeast Asians, including Indonesians. Functional annotation analysis revealed that genes and genetic variants underlying natural selections were generally enriched in the functional category of alternative splicing. Specifically, many genes showing significant difference with respect to allele frequency between northern and southern Asian populations were found to be associated with human height and growth and various immune pathways. In summary, this study contributes to the overall understanding of human local adaptation in Asia and has identified both known and novel signatures of natural selection in the human genome.

Figure 1. Functional categories among pairs of different population groups.

Functional analysis was performed using DAVID annotation. The distribution of significant functional categories among the comparisons covered all the terms meeting a criterion of Benjamini FDR corrected p<0.05. Each color represents one functional term. The y-axis represents the frequency at which the functional term showing significant enrichment occurred in the comparisons of the nine groups in pairs.

Figure 2. Outstanding candidate genes underlying local adaptation show consistency in related population groups.

The genetic distance tree was constructed based on the global F_ST of those 9 groups. The genes shown in circles on the tree were selection signals specific to the corresponding group (as the arrows point). They presented great allele frequency differentiations in the comparisons of local group and other groups joint by the line of the same color (on the right) as the arrow.

Figure 3. Signatures of FOXQ1, MAST2, and CDH4 in the comparison of SouthernChinese&Thai2 and Philippine Negritos.

XP-CLR score was calculated as depicted in the Methods. Against the whole-genome distribution of XP-CLR score, the strongest signals were FOXQ1, CDH4 and MAST2 in the comparison between Philippine Negritos and SouthernChinese&Thai2. The horizontal line indicates a top 50 genome-wide cutoff level.

Figure 4. Signatures of MTTP and DAPP1 in the comparison of Southeast Asian populations with Japanese and Koreans.

SNP-specific F_ST statistic between Japanese&Korean populations and Southeast Asian populations was calculated for each genotyped SNP. MTTP and DAPP1 on chromosome 4 showed significantly high F_ST values. The horizontal line indicates a 1% genome-wide cutoff level.