Malik H S, Bayes J J
Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, A1-162, Seattle, WA 98109, USA.
Biochem Soc Trans. 2006 Aug;34(Pt 4):569-73. doi: 10.1042/BST0340569.
Centromeric DNA evolves rapidly, ranging in size and complexity over several orders of magnitude. Traditional attempts at studying centromeres have left unexplained the causes underlying this complexity and rapid evolution. Instead of directly studying centromeric DNA sequence, our approach has been to study the proteins that epigenetically determine centromere identity. We have discovered that centromeric histones (CenH3s) have evolved under positive selection in multiple lineages, suggesting an involvement in recurrent genetic conflict. Our hypothesis is that 'centromere-drive' is the source of this conflict. Under this model, centromeres compete via microtubule attachments for preferential transmission in female meioses occurring in animals and plants. Since only one of four meiotic products will become the egg, this competition confers a selfish advantage to chromosomes that can make more microtubule attachments, resulting in runaway expansions of centromeric satellites. While beneficial to the 'driving' chromosome, these expansions can have deleterious effects on the fitness of an organism and of the species. CenH3s as well as other heterochromatin proteins have evolved under positive selection to suppress the deleterious consequences of 'centromere-drive' by restoring meiotic parity.
着丝粒DNA进化迅速，其大小和复杂度跨越几个数量级。以往对着丝粒的研究未能解释这种复杂性和快速进化背后的原因。我们的方法不是直接研究着丝粒DNA序列，而是研究那些在表观遗传上决定着丝粒身份的蛋白质。我们发现着丝粒组蛋白（CenH3s）在多个谱系中经历了正选择进化，这表明其参与了反复出现的遗传冲突。我们的假设是，“着丝粒驱动”是这种冲突的根源。在这个模型中，着丝粒通过微管附着在动植物雌性减数分裂中竞争优先传递。由于四个减数分裂产物中只有一个会成为卵子，这种竞争赋予了那些能形成更多微管附着的染色体一种自私的优势，导致着丝粒卫星序列失控扩张。虽然这些扩张对着丝粒“驱动”染色体有益，但可能对生物体和物种的适应性产生有害影响。CenH3s以及其他异染色质蛋白通过恢复减数分裂均等性，在正选择下进化以抑制“着丝粒驱动”的有害后果。
