title: Adaptive evolution of testis-specific, recently evolved, clustered miRNAs in Drosophila.
abstract: The propensity of animal miRNAs to regulate targets bearing modest complementarity, most notably via pairing with miRNA positions ∼2-8 (the "seed"), is believed to drive major aspects of miRNA evolution. First, minimal targeting requirements have allowed most conserved miRNAs to acquire large target cohorts, thus imposing strong selection on miRNAs to maintain their seed sequences. Second, the modest pairing needed for repression suggests that evolutionarily nascent miRNAs may generally induce net detrimental, rather than beneficial, regulatory effects. Hence, levels and activities of newly emerged miRNAs are expected to be limited to preserve the status quo of gene expression. In this study, we unexpectedly show that Drosophila testes specifically express a substantial miRNA population that contravenes these tenets. We find that multiple genomic clusters of testis-restricted miRNAs harbor recently evolved miRNAs, whose experimentally verified orthologs exhibit divergent sequences, even within seed regions. Moreover, this class of miRNAs exhibits higher expression and greater phenotypic capacities in transgenic misexpression assays than do non-testis-restricted miRNAs of similar evolutionary age. These observations suggest that these testis-restricted miRNAs may be evolving adaptively, and several methods of evolutionary analysis provide strong support for this notion. Consistent with this, proof-of-principle tests show that orthologous miRNAs with divergent seeds can distinguish target sensors in a species-cognate manner. Finally, we observe that testis-restricted miRNA clusters exhibit extraordinary dynamics of miRNA gene flux in other Drosophila species. Altogether, our findings reveal a surprising tissue-directed influence of miRNA evolution, involving a distinct mode of miRNA function connected to adaptive gene regulation in the testis.
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853, USA Tri-Institutional Training Program in Computational Biology and Medicine, New York, New York 10065, USA.
authors.forename: Jaaved
authors.initials: J
authors.lastname: Mohammed
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Bortolamiol-Becet
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Flynt
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Ilan
authors.initials: I
authors.lastname: Gronau
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Siepel
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D016000:Cluster Analysis; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D015870:Gene Expression; D020869:Gene Expression Profiling; D014644:Genetic Variation; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism*
chemical_list: D035683:MicroRNAs
keywords: Drosophila; microRNA clusters; positive selection; testis specific; tissue specific