Evolution of the let-7 microRNA Family

Abstract

The increase of bodyplan complexity in early bilaterian evolution is correlates with the advent and diversification of microRNAs. These small RNAs guide animal development by regulating temporal transitions in gene expression involved in cell fate choices and transitions between pluripotency and differentiation. One of the two known microRNAs whose origins date back before the bilaterian ancestor is mir-100. In Bilateria, it appears stably associated in polycistronic transcripts with let-7 and mir-125, two key regulators of development. In vertebrates, these three microRNA families have expanded to form a complex system of developmental regulators. In this contribution, we disentangle the evolutionary history of the let-7 locus, which was restructured independently in nematodes, platyhelminths, and deuterostomes. The foundation of a second let-7 locus in the common ancestor of vertebrates and urochordates predates the vertebrate-specific genome duplications, which then caused a rapid expansion of the let-7 family.

Fast-evolving microRNAs are highly expressed in the early embryo of Drosophila virilis

“…Using covariance model searches and taking into account synteny information, we uncovered numerous homology relationships that have so far escaped sequence similarity detection. We, therefore, strongly argue for the importance of these methods in the analysis of the complex evolutionary history of microRNA families and their use as markers to infer phylogeny (also discussed in Hertel et al 2012). Second, because of their short sequence, some microRNAs diverge to the point where they cannot be confidently identified as homologs.…”

The miRnome of Fasciola hepatica juveniles endorses the existence of a reduced set of highly divergent micro RNAs in parasitic flatworms

“…In several metazoans, miR-125 is part of a genomic cluster that also includes the precursors for miR-100 and let-7. Interestingly, let-7 and miR-125 are clustered in S. mansoni and in the planarian S. mediterranea (Hertel et al, 2012), but they are separated in the genomes of the cestodes, while miR-100 is absent from all flatworms analysed to date (Jin et al, 2013). Let-7 is the third most highly expressed miRNA in NEJs, if we consider a novel variant of let-7 (let-7c) which is poorly conserved out of the seed region (Table 1).…”

Evolution of themiR199-214cluster and vertebrate skeletal development

“…7 The increase of body plan complexity in early bilaterian, vertebrate, and mammalian evolution is correlated with the increasing number and diversification of microRNAs. [8][9][10] The origin and evolution of only a few miR families have been inferred, [11][12][13][14] but the evolutionary mechanisms underlying the emergence of novel miRs, duplication of existing miRs, and retention or loss of miR duplicates remain unclear.…”