Ancestry-Specific Analyses Reveal Differential Demographic Histories and Opposite Selective Pressures in Modern South Asian Populations.

Genetic variation in contemporary South Asian populations follows a northwest to southeast decreasing cline of shared West Eurasian ancestry. A growing body of ancient DNA evidence is being used to build increasingly more realistic models of demographic changes in the last few thousand years. Through high-quality modern genomes, these models can be tested for gene and genome level deviations. Using local ancestry deconvolution and masking, we reconstructed population-specific surrogates of the two main ancestral components for more than 500 samples from 25 South Asian populations and showed our approach to be robust via coalescent simulations. Our f3 and f4 statistics-based estimates reveal that the reconstructed haplotypes are good proxies for the source populations that admixed in the area and point to complex interpopulation relationships within the West Eurasian component, compatible with multiple waves of arrival, as opposed to a simpler one wave scenario. Our approach also provides reliable local haplotypes for future downstream analyses. As one such example, the local ancestry deconvolution in South Asians reveals opposite selective pressures on two pigmentation genes (SLC45A2 and SLC24A5) that are common or fixed in West Eurasians, suggesting post-admixture purifying and positive selection signals, respectively.

Genetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents.

Gene variants in the UGT1A1 gene are strongly associated with circulating bilirubin levels in several populations, as well as other variants of modest effect across the genome. However, the effects of such variants are unknown regarding the Native American ancestry of the admixed Latino population. Our objective was to assess the Native American genetic determinants of serum bilirubin in Chilean admixed adolescents using the local ancestry deconvolution approach. We measured total serum bilirubin levels in 707 adolescents of the Chilean Growth and Obesity Cohort Study (GOCS) and performed high-density genotyping using the Illumina-MEGA array (>1.7 million genotypes). We constructed a local ancestry reference panel with participants from the 1000 Genomes Project, the Human Genome Diversity Project, and our GOCS cohort. Then, we inferred and isolated haplotype tracts of Native American, European, or African origin to perform genome-wide association studies. In the whole cohort, the rs887829 variant and others near UGT1A1 were the unique signals achieving genome-wide statistical significance (b = 0.30; p = 3.34 × 10-57). After applying deconvolution methods, we found that significance is also maintained in Native American (b = 0.35; p = 3.29 × 10-17) and European (b = 0.28; p = 1.14 × 10-23) ancestry components. The rs887829 variant explained a higher percentage of the variance of bilirubin in the Native American (37.6%) compared to European ancestry (28.4%). In Native American ancestry, carriers of the TT genotype of this variant averaged 4-fold higher bilirubinemia compared to the CC genotype (p = 2.82 × 10-12). We showed for the first time that UGT1A1 variants are the primary determinant of bilirubin levels in Native American ancestry, confirming its pan-ethnic relevance. Our study illustrates the general value of the local ancestry deconvolution approach to assessing isolated ancestry effects in admixed populations.

Extent of wild-to-crop interspecific introgression in grapevine (Vitis vinifera) as a consequence of resistance breeding and implications for the crop species definition.

Over the past two centuries, introgression through repeated backcrossing has introduced disease resistance from wild grape species into the domesticated lineage Vitis vinifera subsp. sativa. Introgression lines are being cultivated over increasing vineyard surface areas, as their wines now rival in quality those obtained from preexisting varieties. There is, however, a lot of debate about whether and how wine laws defining commercial product categories, which are based on the classification of V. vinifera and interspecific hybrid grapes, should be revised to accommodate novel varieties that do not fit either category. Here, we developed a method of multilocus genotype analysis using short-read resequencing to identify haplotypic blocks of wild ancestry in introgression lines and quantify the physical length of chromosome segments free-of-introgression or with monoallelic and biallelic introgression. We used this genomic data to characterize species, hybrids and introgression lines and show that newly released resistant varieties contain 76.5-94.8% of V. vinifera DNA. We found that varietal wine ratings are not always commensurate with the percentage of V. vinifera ancestry and linkage drag of wild alleles around known resistance genes persists over at least 7.1-11.5 Mb, slowing down the recovery of the recurrent parental genome. This method also allowed us to identify the donor species of known resistance haplotypes, define the ancestry of wild genetic background in introgression lines with complex pedigrees, validate the ancestry of the historic varieties Concord and Norton, and unravel sample curation errors in public databases.