Computational identification and characterization of primate-specific microRNAs in human genome

Sheng Lin, William K C Cheung, Shen Chen, Gang Lu, Zifeng Wang, Dan Xie, Kui Li, Marie C M Lin, Hsiang-Fu Kung
Computational Biology and Chemistry 2010, 34 (4): 232-41
A number of microRNAs (miRNAs) that are evolutionarily conserved not beyond primate lineage have been identified. These primate-specific miRNAs (ps-miRNAs) may attribute to the difference between high-level primates and non-primate mammals or lower vertebrates. Despite of their importance, the genome-wide miRNA conservation patterns and the properties of these ps-miRNAs are largely elusive. In this study, we developed a robust classification system to assess the conservation pattern of all human mature miRNAs across 44 vertebrate genomes. By this comparative genomic analysis, a novel set of 269 ps-miRNAs were identified. We found that many ps-miRNAs were enriched in chromosome 19 and X, forming two main clusters hereafter referred as C19MC and CXMC, respectively. When comparing the seed of ps-miRNAs themselves or with non-ps-miRNAs, more than one half ps-miRNAs sharing common seeds were belonged to C19MC, 9 of which retained a unique seed that had been reported to be enriched in human embryonic stem cells (hESCs) specific miRNAs. Moreover, the most abundant ps-miRNA common seed was possessed by miR-548 family. Most ps-miRNAs had very low expression in adult tissues, which may be attributed to temporal and spatial specific transcript regulation. The ps-miRNAs with relatively high expression were mainly belonged to C19MC and CXMC, and preferentially expressed in hESCs and reproductive system. Sequence anatomy revealed that C19MC ps-miRNAs were highly conserved but not beyond primates and of great sequence similarity. Gene Ontology and KEGG pathway enrichment analyses of predicted target genes indicated that C19MC ps-miRNAs were strongly associated with developmental processes and various cancers. In conclusion, ps-miRNAs may play critical roles in differentiation and growth regulation during early development, especially in maintaining the pluripotency of hESCs. Results from this study may help explaining the differences between primates and lower vertebrates at genetic level.

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