An evolutionary history of the selectin gene cluster in humans

Molecules involved in leukocyte trafficking have a central role in the development of inflammatory and immune responses. We performed FST analysis of the selectin cluster, as well as of SELPLG, ICAM1 and VCAM1. Peaks of significantly high population genetic differentiation were restricted to two regions in SELP and one in SELPLG. Resequencing data indicated that the region covering SELP exons 11–13 displays high nucleotide diversity in Africans and Europeans (CEU), and a high level of within-species diversity compared with inter-specific divergence. Analysis of inferred haplotypes revealed a complex phylogeny with two deeply separated clades that coalesce at ~3.5 million years (MY) plus a minor clade with a TMRCA (time to the most recent common ancestor) of ~2.2 MY. A splicing assay indicated no haplotype-specific effect on SELP exon 14 inclusion. These data are consistent with a model of multiallelic balancing selection; single-nucleotide polymorphism analysis indicated that the Val640...参与白细胞迁移（leukocyte trafficking）的分子在炎症与免疫应答的发生过程中发挥核心作用。我们针对选择素家族簇（selectin cluster）、SELPLG、ICAM1以及VCAM1开展了固定指数（Fixation Index, FST）分析。群体遗传分化显著升高的峰值仅局限于SELP基因的两个区域与SELPLG基因的一个区域。重测序数据显示，覆盖SELP基因第11~13号外显子的区域在非洲人群与欧洲血统CEU人群中呈现出较高的核苷酸多样性，且相较于种间分化水平，该区域的种内多样性程度更高。对推断得到的单倍型（haplotype）进行系统发育分析后，我们发现了一个复杂的系统发育结构：包含两个分化程度极高的进化枝（clade），二者的溯祖时间约为350万年（million years, MY），此外还存在一个次要进化枝，其最近共同祖先时间（time to the most recent common ancestor, TMRCA）约为220万年（million years, MY）。剪接实验结果表明，单倍型对SELP基因第14号外显子的剪接保留无特异性影响。上述数据与多等位基因平衡选择的模型相符；单核苷酸多态性（single-nucleotide polymorphism, SNP）分析结果显示，Val640……