Parallel pathways for recruiting effector proteins determine centromere drive and suppression.
Parallel pathways for recruiting effector proteins determine centromere drive and suppression.
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DOI：
10.1016/j.cell.2021.07.037
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发表时间：
2021-09-16
期刊：
影响因子：
64.5
通讯作者：
Lampson MA
中科院分区：
文献类型：
--
作者：
Kumon T;Ma J;Akins RB;Stefanik D;Nordgren CE;Kim J;Levine MT;Lampson MA
在雌性减数分裂中，自私的着丝粒DNA序列将它们的传递偏向卵子。进化论认为着丝粒蛋白的进化是为了抑制这种“着丝粒驱动”的成本。在母系和父系着丝粒基因不同的杂交小鼠模型中，自私的着丝粒DNA利用动粒途径招募微管破坏稳定的蛋白作为驱动效应器。我们发现，这种功能差异被异染色质重新招募效应器的平行途径所抑制，这与该系统中着丝粒之间的途径类似。用CENP-C的不同等位基因扰乱着丝粒途径可以减少着丝粒之间的功能差异，而通过CENP-B缺失扰乱异染色质则会放大这些差异。利用Murinae基因组进行的分子进化分析确定了这两条途径中蛋白质的适应性进化。我们认为，着丝粒蛋白的反复进化使自私DNA利用的动粒途径相对于平衡着丝粒的异染色质途径最小化，同时保持基本功能。着丝粒蛋白的循环进化通过平衡促进和抑制自私序列驱动的途径，最小化了遗传上不同的着丝粒之间的功能差异。
Selfish centromere DNA sequences bias their transmission to the egg in female meiosis. Evolutionary theory suggests that centromere proteins evolve to suppress costs of this “centromere drive”. In hybrid mouse models with genetically different maternal and paternal centromeres, selfish centromere DNA exploits a kinetochore pathway to recruit microtubule-destabilizing proteins that act as drive effectors. We show that such functional differences are suppressed by a parallel pathway for effector recruitment by heterochromatin, which is similar between centromeres in this system. Disrupting the kinetochore pathway with a divergent allele of CENP-C reduces functional differences between centromeres, whereas disrupting heterochromatin by CENP-B deletion amplifies the differences. Molecular evolution analyses using Murinae genomes identify adaptive evolution in proteins in both pathways. We propose that centromere proteins have recurrently evolved to minimize the kinetochore pathway, which is exploited by selfish DNA, relative to the heterochromatin pathway that equalizes centromeres, while maintaining essential functions. Recurrent evolution of centromere proteins minimizes functional differences between genetically different centromeres by balancing the pathways that promote and suppress drive by selfish sequences.
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