Guo Xuejiang, Su Bing, Zhou Zuomin, Sha Jiahao
Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, PR China.
BMC Genomics. 2009 Mar 4;10:97. doi: 10.1186/1471-2164-10-97.
MicroRNAs (miRNAs), which are small, non-coding RNAs approximately 21-nucleotides in length, have become a major focus of research in molecular biology. Mammalian miRNAs are proposed to regulate approximately 30% of all protein-coding genes. Previous studies have focused on highly conserved miRNAs, but nonconserved miRNAs represent a potentially important source of novel functionalities during evolution.
An analysis of the chromosome distribution of miRNAs showed higher densities of miRNAs on the X chromosome compared to the average densities on autosomes in all eight mammalian species analyzed. The distribution pattern did not, however, apply well to species beyond mammals. In addition, by comparing orthologous human and mouse miRNAs, we found that X-linked miRNAs had higher substitution rates than autosomal miRNAs. Since the highest proportion of X-linked miRNAs were found in mouse testis, we tested the hypothesis that testis miRNAs are evolving faster on the X chromosome than on autosomes. Mature X-linked testis miRNAs had an average substitution rate between mouse and human that was almost 25-fold higher than mature testis miRNAs on autosomes. In contrast, for mature miRNAs with precursors not expressed in testis, no significant difference in the substitution rate between the X chromosome and autosomes was found. Among mammals, the rapid evolution of X-linked testis miRNAs was also observed in rodents and primates.
The rapid evolution of X-linked testis miRNAs implies possible important male reproductive functions and may contribute to speciation in mammals.
微小RNA(miRNA)是长度约为21个核苷酸的小型非编码RNA,已成为分子生物学研究的主要焦点。据推测,哺乳动物的miRNA可调控约30%的所有蛋白质编码基因。以往的研究主要集中在高度保守的miRNA上,但非保守miRNA在进化过程中可能是新功能的重要来源。
对miRNA的染色体分布分析表明,在所有分析的八个哺乳动物物种中,X染色体上miRNA的密度高于常染色体上的平均密度。然而,这种分布模式并不适用于哺乳动物以外的物种。此外,通过比较直系同源的人类和小鼠miRNA,我们发现X连锁的miRNA比常染色体miRNA具有更高的替换率。由于在小鼠睾丸中发现X连锁miRNA的比例最高,我们检验了睾丸miRNA在X染色体上比在常染色体上进化更快的假设。成熟的X连锁睾丸miRNA在小鼠和人类之间的平均替换率几乎比常染色体上成熟的睾丸miRNA高25倍。相比之下,对于前体在睾丸中不表达的成熟miRNA,在X染色体和常染色体之间未发现替换率有显著差异。在哺乳动物中,啮齿动物和灵长类动物也观察到X连锁睾丸miRNA的快速进化。
X连锁睾丸miRNA的快速进化意味着可能具有重要的雄性生殖功能,并可能有助于哺乳动物的物种形成。