Sun Miao, Hurst Laurence D, Carmichael Gordon G, Chen Jianjun
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Genome Res. 2006 Jul;16(7):922-33. doi: 10.1101/gr.5210006. Epub 2006 Jun 12.
Given that humans have about the same number of genes as mice and not so many more than worm, what makes us more complex? Antisense transcripts are implicated in many aspects of gene regulation. Is there a functional connection between antisense transcription and organismic complexity, that is, is antisense regulation especially prevalent in humans? We used the same robust protocol to identify antisense transcripts in humans and five other metazoan genomes (mouse, rat, chicken, fruit fly, and nematode), and found that the estimated proportions of genes involved in antisense transcription are highly sensitive to the number of transcripts included in the analysis. By controlling for transcript abundance, we find that the probability that any given transcript is putatively involved in sense-antisense regulation is no higher in humans than in other vertebrates but appears unusually high in flies and especially low in nematodes. Similarly, there is no evidence that the proportion of sense-antisense transcripts is especially higher in humans than other vertebrates in a given subset of transcript sequences such as mRNAs, coding sequences, conserved, or nonconserved transcripts. Although antisense transcription might be enriched in mammalian brains compared with nonbrain tissues, it is no more enriched in human brain than in mouse brain. Overall, therefore, while we see striking variation between multicellular animals in the abundance of antisense transcripts, there is no evidence for a link between antisense transcription and organismic complexity. More particularly, we see no evidence that humans are in any way unusual among the vertebrates in this regard. Instead, our results suggest that antisense transcription might be prevalent in almost all metazoan genomes, nematodes being an unexplained exception.
鉴于人类的基因数量与小鼠大致相同，比线虫多不了多少，那是什么让我们更复杂呢？反义转录本与基因调控的许多方面都有关联。反义转录与生物体复杂性之间是否存在功能联系，也就是说，反义调控在人类中是否特别普遍？我们使用相同可靠的方案在人类和其他五个后生动物基因组（小鼠、大鼠、鸡、果蝇和线虫）中鉴定反义转录本，发现参与反义转录的基因估计比例对分析中包含的转录本数量高度敏感。通过控制转录本丰度，我们发现任何给定转录本可能参与正义-反义调控的概率在人类中并不比其他脊椎动物高，但在果蝇中似乎异常高，而在线虫中尤其低。同样，没有证据表明在给定的转录本序列子集（如mRNA、编码序列、保守或非保守转录本）中，正义-反义转录本的比例在人类中比其他脊椎动物特别高。虽然与非脑组织相比，反义转录可能在哺乳动物大脑中富集，但在人类大脑中的富集程度并不比小鼠大脑更高。因此，总体而言，虽然我们看到多细胞动物之间反义转录本丰度存在显著差异，但没有证据表明反义转录与生物体复杂性之间存在联系。更具体地说，我们没有证据表明人类在这方面在脊椎动物中有任何异常。相反，我们的结果表明反义转录可能在几乎所有后生动物基因组中普遍存在，线虫是一个无法解释的例外。
