Institute of Molecular Evolutionary Genetics, Department of Biology, Pennsylvania State University, USA.
Genome Biol Evol. 2011;3:129-39. doi: 10.1093/gbe/evq088. Epub 2010 Dec 27.
MicroRNAs (miRs) are noncoding RNAs that regulate gene expression at the post-transcriptional level. In animals, the target sites of a miR are generally located in the 3' untranslated regions (UTRs) of messenger RNAs. However, how the target sites change during evolution is largely unknown. MiR-iab-4 and miR-iab-4as are known to regulate the expression of two Hox genes, Abd-A and Ubx, in Drosophila melanogaster. We have therefore studied the evolutionary changes of these two miR genes and their target sites of the Hox genes in Drosophila, other insect species, and Daphnia. Our homology search identified a single copy of each miR gene located in the same genomic position of the Hox gene cluster in all species examined. The seed nucleotide sequence was also the same for all species. Searching for the target sites in all Hox genes, we found several target sites of miR-iab-4 and miR-iab-4as in Antp in addition to Abd-A and Ubx in most insect species examined. Our phylogenetic analysis of target sites in Abd-A, Ubx, and Antp showed that the old target sites, which existed before the divergence of the 12 Drosophila species, have been well maintained in most species under purifying selection. By contrast, new target sites, which were generated during Drosophila evolution, were often lost in some species and mostly located in unalignable regions of the 3' UTRs. These results indicate that these regions can be a potential source of generating new target sites, which results in multiple target genes for each miR in animals.
MicroRNAs (miRs) 是一类非编码 RNA，可在转录后水平调控基因表达。在动物中，miR 的靶位点通常位于信使 RNA 的 3'非翻译区 (UTR)。然而，miR 的靶位点在进化过程中如何发生变化，目前还知之甚少。miR-iab-4 和 miR-iab-4as 已知可调节果蝇中两个 Hox 基因 Abd-A 和 Ubx 的表达。因此，我们研究了这两个 miR 基因及其在果蝇、其他昆虫物种和溞类中的 Hox 基因靶位点的进化变化。我们的同源性搜索在所有检查的物种中，在 Hox 基因簇的相同基因组位置鉴定到每个 miR 基因的单个拷贝。所有物种的种子核苷酸序列也相同。在所有 Hox 基因中搜索靶位点时，我们在 Antp 中发现了 miR-iab-4 和 miR-iab-4as 的几个靶位点，除了大多数检查的昆虫物种中的 Abd-A 和 Ubx 之外。我们对 Abd-A、Ubx 和 Antp 的靶位点的系统发育分析表明，在 12 个果蝇物种分化之前存在的旧靶位点，在大多数物种中已通过纯化选择得到很好的保留。相比之下，在果蝇进化过程中产生的新靶位点，在一些物种中经常丢失，并且主要位于 3'UTR 的未对齐区域。这些结果表明，这些区域可能是产生新靶位点的潜在来源，从而导致动物中每个 miR 具有多个靶基因。
