Run or Die in the Evolution of New MicroRNAs—Testing the Red Queen Hypothesis on De Novo New Genes

Abstract

The Red Queen hypothesis depicts evolution as the continual struggle to adapt. According to this hypothesis, new genes, especially those originating from nongenic sequences (i.e., de novo genes), are eliminated unless they evolve continually in adaptation to a changing environment. Here, we analyze two Drosophila de novo miRNAs that are expressed in a testis-specific manner with very high rates of evolution in their DNA sequence. We knocked out these miRNAs in two sibling species and investigated their contributions to different fitness components. We observed that the fitness contributions of miR-975 in Drosophila simulans seem positive, in contrast to its neutral contributions in D. melanogaster, whereas miR-983 appears to have negative contributions in both species, as the fitness of the knockout mutant increases. As predicted by the Red Queen hypothesis, the fitness difference of these de novo miRNAs indicates their different fates.

Spatiotemporal Regulation of a Single Adaptively EvolvingTrans-Regulatory Element Contributes to Spermatogenetic Expression Divergence inDrosophila

“…We and others previously reported that miR-983 has evolved adaptively in both D. melanogaster and D. simulans ( Lyu et al 2014 ; Mohammed et al 2014 ). Consistent with the expectation of distinct seed sequences, which are crucial for target recognition ( Agarwal et al 2018 ), loss-of-function mutants of miR-983 exhibit divergent mis-expression of genes between D. melanogaster and D. simulans ( Zhao et al 2021 ). However, it is unclear whether such divergence is caused by changes in miR-983 or in genomic contexts.…”

“…To overcome the caveats of previous approaches, we used gene replacement and single-cyst RNA-seq analysis. The trans -regulatory element we analyzed is an adaptively evolving microRNA (miRNA), miR-983, which shows sequence divergence between Drosophila species ( Lyu et al 2014 ; Mohammed et al 2014 ), possesses a large number of targets, exhibits testis-preferential expression ( Lyu et al 2014 ; Mohammed et al 2014 ; Mohammed et al 2018 ), and affects different components of male fitness ( Lu et al 2018 ; Zhao et al 2021 ) so is suitable for this study. Our results suggest that despite antagonism with the often-predominant cis effects, trans regulators may reduce pleiotropy and respond to natural selection via spatiotemporally specific regulation.…”

A Rapid Evolving microRNA Cluster Rewires Its Target Regulatory Networks in Drosophila

“…New genes continuously contribute to genetic novelty and offer a unique opportunity to understand the phenotypic divergence between species and the evolution of genetic regulatory networks (Tang et al, 2010;Chen et al, 2012;Ross et al, 2013;Zhao et al, 2021). As key players in gene regulation, miRNAs repress their targets weakly but broadly in animals (Zhao et al, 2017;Chen et al, 2019).…”

“…The long-term survival of these novel miRNAs remains unclear. Previously we have shown that miR-975 exerts different influences on male fertility between D. melanogaster and D. simulans, and its lossof-function might be adaptive in some lineages (Lu et al, 2018a(Lu et al, , 2018bZhao et al, 2021). Another good example in Drosophila is the mir-310/311/312/313 cluster (mir-310C), which is another adaptive miRNA cluster with a same age as mir-972C (Lu et al, 2008;Lyu et al, 2014).…”

“…Among the members of miR-972C, miR-975 is especially intriguing as it has distinct effects on male reproduction between D. melanogaster and D. simulans (Zhao et al, 2021), and thus offers an opportunity to study the functional evolution of miRNAs. mir-975 has undergone substitutions in both seed and non-seed regions (Figure 2A, Supplementary Figure S1).…”