The life history of retrocopies illuminates the evolution of new mammalian genes.
The life history of retrocopies illuminates the evolution of new mammalian genes.
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DOI：
10.1101/gr.198473.115
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发表时间：
2016-03
期刊：
影响因子：
7
通讯作者：
Kaessmann H
中科院分区：
文献类型：
--
作者：
Carelli FN;Hayakawa T;Go Y;Imai H;Warnefors M;Kaessmann H
新基因对适应性进化创新做出了重大贡献，但哺乳动物新基因的功能进化却很少在大范围内得到探索。先前的工作建立了mrna衍生的基因复制，即逆转录，作为研究新基因起源的模型。在这里，我们结合了哺乳动物转录组学和表观基因组学的数据，揭示了剥离的逆转录成复杂的新基因的进化过程。我们发现，尽管一些健壮表达的逆转录拷贝是从先前存在的启动子转录而来，但大多数从头开始进化新的启动子或在其基因组附近招募原启动子。特别是，许多逆转录启动子来自祖先的增强子（或二价调控元件）或位于与其他基因无关的CpG岛。我们在每个哺乳动物物种中检测到88-280个选择性保存的逆转录拷贝，说明这些机制促进了哺乳动物进化过程中许多功能性逆转录基因的诞生。最初的单外显子逆转录的调控进化经常伴随着外显子的获得，这促进了远端启动子的共选择，并允许替代同种异构体的表达。虽然年轻的逆转录基因通常最初在睾丸中表达，但增加的调节和结构复杂性允许逆转录基因在功能上多样化和进化成体细胞器官功能，有时与其父母一样复杂。因此，在雄性减数分裂X失活过程中，一些逆转录基因进化出了暂时替代亲本的能力，而另一些逆转录基因则使亲本功能变得多余，从而导致亲本基因的丢失。总的来说，我们对哺乳动物逆转录基因“生活史”的重建突出了逆转录作为理解新基因诞生和功能进化的一般模型。
New genes contribute substantially to adaptive evolutionary innovation, but the functional evolution of new mammalian genes has been little explored at a broad scale. Previous work established mRNA-derived gene duplicates, known as retrocopies, as models for the study of new gene origination. Here we combine mammalian transcriptomic and epigenomic data to unveil the processes underlying the evolution of stripped-down retrocopies into complex new genes. We show that although some robustly expressed retrocopies are transcribed from preexisting promoters, most evolved new promoters from scratch or recruited proto-promoters in their genomic vicinity. In particular, many retrocopy promoters emerged from ancestral enhancers (or bivalent regulatory elements) or are located in CpG islands not associated with other genes. We detected 88–280 selectively preserved retrocopies per mammalian species, illustrating that these mechanisms facilitated the birth of many functional retrogenes during mammalian evolution. The regulatory evolution of originally monoexonic retrocopies was frequently accompanied by exon gain, which facilitated co-option of distant promoters and allowed expression of alternative isoforms. While young retrogenes are often initially expressed in the testis, increased regulatory and structural complexities allowed retrogenes to functionally diversify and evolve somatic organ functions, sometimes as complex as those of their parents. Thus, some retrogenes evolved the capacity to temporarily substitute for their parents during the process of male meiotic X inactivation, while others rendered parental functions superfluous, allowing for parental gene loss. Overall, our reconstruction of the “life history” of mammalian retrogenes highlights retroposition as a general model for understanding new gene birth and functional evolution.