Recurrent Innovation at Genes Required for Telomere Integrity in Drosophila.

Recurrent Innovation at Genes Required for Telomere Integrity in Drosophila.
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果蝇端粒完整性所需基因的反复创新。

DOI:
10.1093/molbev/msw248
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发表时间:
2017-02-01
影响因子:
10.7
通讯作者:
Levine MT
Levine MT
中科院分区:
生物学1区
文献类型:
--
作者:
Lee YC;Leek C;Levine MT

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端粒是位于线性染色体末端的核蛋白复合体。这些特殊的结构确保了基因组的完整性和忠实的染色体遗传。重复的端粒特异性DNA元件反复添加到染色体末端对抗末端磨损,而专门的端粒相关蛋白保护裸露的双链染色体末端免于混杂修复成端对端融合。虽然端粒长度稳态和末端保护在真核生物中普遍存在,但有零星的证据表明支持这些基本过程的分子机制迅速进化。然而,没有对任何真核生物进行过塑造这些快速进化蛋白质的进化力量的全球分析。黑腹果蝇及其近亲丰富的种群和比较基因组资源为我们填补这一空白提供了一个独特的机会。在这里,我们利用群体遗传学,分子进化和端粒基因组学来定义范围和进化机制,推动端粒完整性所需的基因的快速进化。我们发现了在多个进化时间尺度上普遍存在的正选择的证据。我们还记录了端粒蛋白建立的基因家族的多产扩张,营业额和表达进化。受这些快速进化基因的突变表型和分子作用的启发,我们提出了四种可供选择的,但不是相互排斥的,可能在真核染色体末端发生基因组内冲突的模型。我们的发现为研究果蝇及其他动物端粒蛋白进化的遗传原因和功能后果奠定了基础。
Telomeres are nucleoprotein complexes at the ends of linear chromosomes. These specialized structures ensure genome integrity and faithful chromosome inheritance. Recurrent addition of repetitive, telomere-specific DNA elements to chromosome ends combats end-attrition, while specialized telomere-associated proteins protect naked, double-stranded chromosome ends from promiscuous repair into end-to-end fusions. Although telomere length homeostasis and end-protection are ubiquitous across eukaryotes, there is sporadic but building evidence that the molecular machinery supporting these essential processes evolves rapidly. Nevertheless, no global analysis of the evolutionary forces that shape these fast-evolving proteins has been performed on any eukaryote. The abundant population and comparative genomic resources of Drosophila melanogaster and its close relatives offer us a unique opportunity to fill this gap. Here we leverage population genetics, molecular evolution, and phylogenomics to define the scope and evolutionary mechanisms driving fast evolution of genes required for telomere integrity. We uncover evidence of pervasive positive selection across multiple evolutionary timescales. We also document prolific expansion, turnover, and expression evolution in gene families founded by telomeric proteins. Motivated by the mutant phenotypes and molecular roles of these fast-evolving genes, we put forward four alternative, but not mutually exclusive, models of intra-genomic conflict that may play out at very termini of eukaryotic chromosomes. Our findings set the stage for investigating both the genetic causes and functional consequences of telomere protein evolution in Drosophila and beyond.
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