Human MicroRNAs Originated from Two Periods at Accelerated Rates in Mammalian Evolution

Abstract

MicroRNAs (miRNAs) are short, noncoding RNAs that modulate genes posttranscriptionally. Frequent gains and losses of miRNA genes have been reported to occur during evolution. However, little is known systematically about the periods of evolutionary origin of the present miRNA gene repertoire of an extant mammalian species. Thus, in this study, we estimated the evolutionary periods during which each of 1,433 present human miRNA genes originated within 15 periods, from human to platypus–human common ancestral branch and a class “conserved beyond theria,” primarily using multiple genome alignments of 38 species, plus the pairwise genome alignments of five species. The results showed two peak periods in which the human miRNA genes originated at significantly accelerated rates. The most accelerated rate appeared in the period of the initial phase of hominoid lineage, and the second appeared shortly before Laurasiatherian divergence. Approximately 53% of the present human miRNA genes have originated within the simian lineage to human. In particular, approximately 28% originated within the hominoid lineage. The early phase of placental mammal radiation comprises approximately 28%, while no more than 15% of human miRNAs have been conserved beyond placental mammals. We also clearly showed a general trend, in which the miRNA expression level decreases as the miRNA becomes younger. Intriguingly, amid this decreasing trend of expression, we found one significant rise in the expression level that corresponded to the initial phase of the hominoid lineage, suggesting that increased functional acquisitions of miRNAs originated at this particular period.

Evolution of themiR199-214cluster and vertebrate skeletal development

“…63,64 Furthermore, the evolution of the complementary strand of miR214 into a functional processed miR, miR3120, reveals a new type of miR emergence by complementarity with the mirrored miR gene. Altogether, the evolution of the miR199-214 cluster provides various examples of duplication, retention, and lineage-specific loss or gain of miR sequences illustrating the range of processes in miR gene evolution.…”

MicroRNA analysis in model species based on evolutionary rates

“…In the mammal lineage, miRNAs seemed to have evolved rapidly, with some newborn miRNAs getting lost while many others with increased expression were conserved in the nervous system, thus displaying robustness in the gene networks (Meunier et al, 2013). Such rapid evolutionary rates have also been observed during the early evolution of marsupials and the late evolutionary history of humans (Iwama et al, 2013). All of these findings indicate that miRNAs are linked to phenotype formation and thus species evolution.…”

“…This suggests that differences in expression levels between young and old miRNAs may have been decreased, and that young miRNAs could have already performed important functions in humans. Iwama et al (2013) reported an increase in miRNA expression that was specific to the initial hominoid lineage. Therefore, fast-evolving miRNAs in humans may have been subjected to high, positive selection pressure, which may not have been the case in the other five species.…”

Comparative genomic analysis of upstream miRNA regulatory motifs in Caenorhabditis

“…Because they can regulate hundreds of target genes (Farh et al 2005;Lewis et al 2005), miRNAs have emerged as key modulators of gene function with links to human disease (Calin et al 2004;Jazdzewski et al 2009) and possible roles in phenotypic innovation (Heimberg et al 2008;Iwama et al 2013;Meunier et al 2013). miRNAs were first identified in the nematode Caenorhabditis elegans through cloning of mutations affecting temporal control of cell fate determination during larval development (Lee et al 1993;Reinhart et al 2000).…”