近日，BMC Genomics杂志在线发表中国科学院水生生物研究所研究员何舜平研究组的一篇研究论文，题为evolutionary fate and implications of retrocopies in the African coelacanth genome。博士研究生杜康为论文第一作者，何舜平研究员为论文通讯作者。

矛尾鱼是现存已知最古老的肉鳍类动物(包括总鳍鱼和四足类)之一，有研究认为它的存在已经超过4亿年。最近的基因组资料显示，在现存物种中，除了肺鱼之外，矛尾鱼是在系统发育上最接近四足类的物种，因此它为3.5亿年前脊椎动物的“登陆”事件提供了重要线索。在脊椎动物“登陆”过程中，其基因组会相应发生动态变化，变化之一就是已有基因的丢失和“新生”基因的加入。“反转座拷贝”就很有可能成为这一过程中新加入基因组的一类“新生”基因。

“反转座拷贝”是某些基因通过转录成RNA再反转录成cdna片段重新插入基因组而形成的该基因的拷贝。这类拷贝只拥有“父”基因的编码片段而丢失了对应的调控序列，因此很长时间被认为是基因组中的“垃圾”。最近研究显示，一些“反转座拷贝”利用它“邻居”基因的调控序列，成功完成了自己的翻译和表达，成为有生物学功能的“反转座基因”。

何舜平带领的学科组利用生物信息学方案，在矛尾鱼基因组中鉴定了472个“反转座拷贝”，通过研究它们的进化年龄、选择压力、表达模式以及相关的基因功能，探讨了它们对脊椎动物“登陆”事件以及矛尾鱼进化的意义。研究结果显示：1)这472个“反转座拷贝”的年龄结构与四足类的“反转座拷贝”相似，而与辐鳍鱼不同，暗示了脊椎动物基因组在“登陆”进化时可能发生了一次相应的动态调整;2)选择压力以及表达的研究结果显示，85~355个“反转座拷贝”是有潜在的生物学功能的“反转座基因”，它们在较大年龄层的“反转座拷贝”中占比更多一些，暗示了一些无功能的“反转座拷贝”在进化过程中会逐渐丢失;3)发现了23个“反转座拷贝”相关基因存在于辐鳍鱼类中，而在四足类丢失，可能与“登陆”进化相关。

原文链接：evolutionary fate and implications of retrocopies in the African coelacanth genome

原文摘要：

Background

The coelacanth is known as a “living fossil” because of its morphological resemblance to its fossil ancestors. Thus, it serves as a useful model that provides insight into the fish that first walked on land. Retrocopies are a type of novel genetic element that are likely to contribute to genome or phenotype innovations. Thus, investigating retrocopies in the coelacanth genome can determine the role of retrocopies in coelacanth genome innovations and perhaps even water-to-land adaptations.

Results

We determined the dS values, dN/dS ratios, expression patterns, and enrichment of functional categories for 472 retrocopies in the African coelacanth genome. Of the retrocopies, 85–355 were shown to be potentially functional (i.e., retrogenes). The distribution of retrocopies based on their dS values revealed a burst pattern of young retrocopies in the genome. The retrocopy birth pattern was shown to be more similar to that in tetrapods than ray-finned fish, which indicates a genomic transformation that accompanied vertebrate evolution from water to land. Among these retrocopies, retrogenes were more prevalent in old than young retrocopies, which indicates that most retrocopies may have been eliminated during evolution, even though some retrocopies survived, attained biological function as retrogenes, and became old. Transcriptome data revealed that many retrocopies showed a biased expression pattern in the testis, although the expression was not specifically associated with a particular retrocopy age range. We identified 225 Ensembl genes that overlapped with the coelacanth genome retrocopies. GO enrichment analysis revealed different overrepresented GO (gene ontology) terms between these “retrocopy-overlapped genes” and the retrocopy parent genes, which indicates potential genomic functional organization produced by retrotranspositions. Among the 225 retrocopy-overlapped genes, we also identified 46 that were coelacanth-specific, which could represent a potential molecular basis for coelacanth evolution.

Conclusions

Our study identified 472 retrocopies in the coelacanth genome. Sequence analysis of these retrocopies and their parent genes, transcriptome data, and GO annotation information revealed novel insight about the potential role of genomic retrocopies in coelacanth evolution and vertebrate adaptations during the evolutionary transition from water to land.