Institute of Genetics and Biophysics, National Research Council, Naples, Italy.
Department of Biology, University of Naples Federico II, Napoli, Italy.
Sci Rep. 2019 Mar 19;9(1):4843. doi: 10.1038/s41598-019-40360-9.
Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation. We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site of ABCA12. We found no obvious effect of rs10180970 alleles on ABCA12 gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and present in non-Africans 45,000 years ago.
自然选择通过增加负责特定环境中有利细胞功能的等位基因的频率来作用于遗传变异。在之前对当代人类正向选择的全基因组扫描中，我们在欧洲人和亚洲人中鉴定到了位于 ABCA12 基因第二内含子中的遗传变异 rs10180970 处的正向选择信号。该变异与脂质屏障形成有关，并且受到 UVB 辐射的下调。我们在包含古代样本 DNA 序列的更大数据集研究了 rs10180970 周围基因组区域的选择信号。我们还研究了在暴露于相似 UV 辐射的健康志愿者中，rs10180970 及其附近另一个遗传变异的等位基因的基因表达的功能后果。我们证实了选择信号，并将其位置精确定位到 35kb 以上，包括 ABCA12 的第一个内含子、前两个外显子和转录起始位点。我们没有发现 rs10180970 等位基因对 ABCA12 基因表达有明显影响。我们重建了过去 80000 年来 T 等位基因的轨迹，发现它是智人特有的，并且在 45000 年前就存在于非非洲人中。
