Max-Delbrück Center for Molecular Medicine, Robert Rössle Str, 10, 13125 Berlin, Germany.
BMC Evol Biol. 2010 Nov 3;10:338. doi: 10.1186/1471-2148-10-338.
Naturally occurring antisense transcripts (NATs) are non-coding RNAs that may regulate the activity of sense transcripts to which they bind because of complementarity. NATs that are not located in the gene they regulate (trans-NATs) have better chances to evolve than cis-NATs, which is evident when the sense strand of the cis-NAT is part of a protein coding gene. However, the generation of a trans-NAT requires the formation of a relatively large region of complementarity to the gene it regulates.
Pseudogene formation may be one evolutionary mechanism that generates trans-NATs to the parental gene. For example, this could occur if the parental gene is regulated by a cis-NAT that is copied as a trans-NAT in the pseudogene. To support this we identified human pseudogenes with a trans-NAT to the parental gene in their antisense strand by analysis of the database of expressed sequence tags (ESTs). We found that the mutations that appeared in these trans-NATs after the pseudogene formation do not show the flat distribution that would be expected in a non functional transcript. Instead, we found higher similarity to the parental gene in a region nearby the 3' end of the trans-NATs.
Our results do not imply a functional relation of the trans-NAT arising from pseudogenes over their respective parental genes but add evidence for it and stress the importance of duplication mechanisms of genetic material in the generation of non-coding RNAs. We also provide a plausible explanation for the large transcripts that can be found in the antisense strand of some pseudogenes.
天然存在的反义转录本（NATs）是非编码 RNA，由于互补性，它们可能会调节与其结合的有意义转录本的活性。与不位于其调节基因（反义 NATs）中的 NATs 相比，反义 NATs 具有更好的进化机会，这在 cis-NAT 的有意义链是编码基因的一部分时更为明显。然而，产生反义 NAT 需要与它所调节的基因形成相对较大的互补区域。
假基因形成可能是产生反义 NATs 到亲本基因的一种进化机制。例如，如果亲本基因受到 cis-NAT 的调节，而 cis-NAT 作为反义链的反义 NAT 被复制到假基因中，就可能发生这种情况。为了支持这一点，我们通过分析表达序列标签（ESTs）数据库，鉴定了人类反义链上具有反义 NAT 的假基因。我们发现，这些反义 NAT 形成后出现在这些反义 NAT 中的突变并没有表现出非功能转录本中预期的平坦分布。相反，我们在反义 NAT 的 3'端附近区域发现了与亲本基因更高的相似性。
我们的结果并不意味着来自假基因的反义 NAT 与其各自的亲本基因之间存在功能关系，但增加了证据支持，并强调了遗传物质复制机制在非编码 RNA 生成中的重要性。我们还为一些假基因反义链中可以发现的大转录本提供了一个合理的解释。
