Department of Evolutionary Studies of Biosystems, School of Advanced Science, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa, 240-0193, Japan.
Research Center for Integrative Evolutionary Science, SOKENDAI, Hayama, Kanagawa, 240-0193, Japan.
Heredity (Edinb). 2023 Aug;131(2):156-169. doi: 10.1038/s41437-023-00631-8. Epub 2023 Jun 23.
Selection on standing genetic variation is important for rapid local genetic adaptation when the environment changes. We report that, for the prostate stem cell antigen (PSCA) gene, different populations have different target haplotypes, even though haplotypes are shared among populations. The C-C-A haplotype, whereby the first C is located at rs2294008 of PSCA and is a low risk allele for gastric cancer, has become a target of positive selection in Asia. Conversely, the C-A-G haplotype carrying the same C allele has become a selection target mainly in Africa. However, Asian and African share both haplotypes, consistent with the haplotype divergence time (170 kya) prior to the out-of-Africa dispersal. The frequency of C-C-A/C-A-G is 0.344/0.278 in Asia and 0.209/0.416 in Africa. Two-dimensional site frequency spectrum analysis revealed that the extent of intra-allelic variability of the target haplotype is extremely small in each local population, suggesting that C-C-A or C-A-G is under ongoing hard sweeps in local populations. From the time to the most recent common ancestor (TMRCA) of selected haplotypes, the onset times of positive selection were recent (3-55 kya), concurrently with population subdivision from a common ancestor. Additionally, estimated selection coefficients from ABC analysis were up to ~3%, similar to those at other loci under recent positive selection. Phylogeny of local populations and TMRCA of selected haplotypes revealed that spatial and temporal switching of positive selection targets is a unique and novel feature of ongoing selection at PSCA. This switching may reflect the potential of rapid adaptability to distinct environments.
当环境发生变化时，选择存在的遗传变异对于快速的局部遗传适应很重要。我们报告称，对于前列腺干细胞抗原（PSCA）基因，尽管不同人群共享单倍型，但不同人群具有不同的目标单倍型。C-C-A 单倍型中，第一个 C 位于 PSCA 的 rs2294008 处，是胃癌的低风险等位基因，已成为亚洲的正选择目标。相反，携带相同 C 等位基因的 C-A-G 单倍型已成为非洲的主要选择目标。然而，亚洲和非洲都共享这两种单倍型，这与非洲以外扩散前的单倍型分化时间（170kya）一致。C-C-A/C-A-G 的频率在亚洲为 0.344/0.278，在非洲为 0.209/0.416。二维位点频率谱分析表明，每个局部人群中目标单倍型的等位基因内变异性程度极小，表明 C-C-A 或 C-A-G 正在局部人群中进行持续的硬选择。从选择单倍型的最近共同祖先（TMRCA）到时间，正选择的开始时间较近（3-55kya），同时伴随着从共同祖先开始的种群分化。此外，ABC 分析估计的选择系数高达约 3%，与其他近期正选择位点的选择系数相似。局部人群的系统发育和选择单倍型的 TMRCA 表明，正选择目标的时空转换是 PSCA 持续选择的一个独特而新颖的特征。这种转换可能反映了对不同环境快速适应的潜力。
