Desvignes Thomas, Sydes Jason, Montfort Jerôme, Bobe Julien, Postlethwait John H
Institute of Neuroscience, University of Oregon, Eugene, OR, USA.
INRAE, LPGP, Rennes, France.
Mol Biol Evol. 2021 Jul 29;38(8):3308-3331. doi: 10.1093/molbev/msab105.
MicroRNAs (miRNAs) are important gene expression regulators implicated in many biological processes, but we lack a global understanding of how miRNA genes evolve and contribute to developmental canalization and phenotypic diversification. Whole-genome duplication events likely provide a substrate for species divergence and phenotypic change by increasing gene numbers and relaxing evolutionary pressures. To understand the consequences of genome duplication on miRNA evolution, we studied miRNA genes following the teleost genome duplication (TGD). Analysis of miRNA genes in four teleosts and in spotted gar, whose lineage diverged before the TGD, revealed that miRNA genes were retained in ohnologous pairs more frequently than protein-coding genes, and that gene losses occurred rapidly after the TGD. Genomic context influenced retention rates, with clustered miRNA genes retained more often than nonclustered miRNA genes and intergenic miRNA genes retained more frequently than intragenic miRNA genes, which often shared the evolutionary fate of their protein-coding host. Expression analyses revealed both conserved and divergent expression patterns across species in line with miRNA functions in phenotypic canalization and diversification, respectively. Finally, major strands of miRNA genes experienced stronger purifying selection, especially in their seeds and 3'-complementary regions, compared with minor strands, which nonetheless also displayed evolutionary features compatible with constrained function. This study provides the first genome-wide, multispecies analysis of the mechanisms influencing metazoan miRNA evolution after whole-genome duplication.
微小RNA（miRNA）是重要的基因表达调控因子，参与许多生物学过程，但我们对miRNA基因如何进化以及如何促进发育稳态和表型多样化缺乏全面的了解。全基因组复制事件可能通过增加基因数量和减轻进化压力为物种分化和表型变化提供一个基础。为了了解基因组复制对miRNA进化的影响，我们研究了硬骨鱼全基因组复制（TGD）后的miRNA基因。对四种硬骨鱼和在TGD之前其谱系就已分化的雀鳝中的miRNA基因进行分析，结果显示，与蛋白质编码基因相比，miRNA基因以同源基因对的形式保留下来的频率更高，而且在TGD之后基因丢失迅速发生。基因组背景影响保留率，成簇的miRNA基因比非成簇的miRNA基因保留得更频繁，基因间miRNA基因比基因内miRNA基因保留得更频繁，基因内miRNA基因通常与其蛋白质编码宿主具有相同的进化命运。表达分析揭示了跨物种保守和不同的表达模式，分别与miRNA在表型稳态和多样化中的功能一致。最后，与次要链相比，主要链的miRNA基因经历了更强的纯化选择，尤其是在其种子区和3'互补区域，不过次要链也显示出与功能受限相一致的进化特征。这项研究首次对全基因组复制后影响后生动物miRNA进化的机制进行了全基因组、多物种分析。
