Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2009 Dec 30;4(12):e8505. doi: 10.1371/journal.pone.0008505.
Recent work indicates that allelic incompatibility in the mouse PRDM9 (Meisetz) gene can cause hybrid male sterility, contributing to genetic isolation and potentially speciation. The only phenotype of mouse PRDM9 knockouts is a meiosis I block that causes sterility in both sexes. The PRDM9 gene encodes a protein with histone H3(K4) trimethyltransferase activity, a KRAB domain, and a DNA-binding domain consisting of multiple tandem C2H2 zinc finger (ZF) domains. We have analyzed human coding polymorphism and interspecies evolutionary changes in the PRDM9 gene. The ZF domains of PRDM9 are evolving very rapidly, with compelling evidence of positive selection in primates. Positively selected amino acids are predominantly those known to make nucleotide specific contacts in C2H2 zinc fingers. These results suggest that PRDM9 is subject to recurrent selection to change DNA-binding specificity. The human PRDM9 protein is highly polymorphic in its ZF domains and nearly all polymorphisms affect the same nucleotide contact residues that are subject to positive selection. ZF domain nucleotide sequences are strongly homogenized within species, indicating that interfinger recombination contributes to their evolution. PRDM9 has previously been assumed to be a transcription factor required to induce meiosis specific genes, a role that is inconsistent with its molecular evolution. We suggest instead that PRDM9 is involved in some aspect of centromere segregation conflict and that rapidly evolving centromeric DNA drives changes in PRDM9 DNA-binding domains.
最近的研究表明，小鼠 PRDM9（Meisetz）基因的等位基因不兼容可能导致杂种雄性不育，从而促进遗传隔离和潜在的物种形成。小鼠 PRDM9 敲除的唯一表型是减数分裂 I 阻滞，导致雌雄两性不育。PRDM9 基因编码一种具有组蛋白 H3（K4）三甲基转移酶活性、KRAB 结构域和由多个串联 C2H2 锌指（ZF）结构域组成的 DNA 结合结构域的蛋白质。我们分析了人类编码多态性和 PRDM9 基因在种间进化中的变化。PRDM9 的 ZF 结构域进化非常迅速，在灵长类动物中存在强烈的正选择证据。正选择的氨基酸主要是那些已知在 C2H2 锌指中与核苷酸特异性结合的氨基酸。这些结果表明，PRDM9 受到反复选择以改变 DNA 结合特异性。人类 PRDM9 蛋白在其 ZF 结构域中高度多态性，几乎所有的多态性都影响到受正选择影响的相同核苷酸结合残基。ZF 结构域核苷酸序列在物种内强烈同质化，表明指间重组有助于其进化。PRDM9 以前被认为是一种转录因子，需要诱导减数分裂特异性基因，但其分子进化与其不一致。相反，我们认为 PRDM9 参与着着丝粒分离冲突的某些方面，而快速进化的着丝粒 DNA 导致 PRDM9 DNA 结合结构域的变化。
