RT Journal A1 Lu, Guang-An A1 Zhao, Yixin A1 Yang, Hao A1 Lan, Ao A1 Shi, Suhua A1 Liufu, Zhongqi A1 Huang, Yumei A1 Tang, Tian A1 Xu, Jin A1 Shen, Xu A1 Wu, Chung-I T1 Death of new microRNA genes in Drosophila via gradual loss of fitness advantages JF Genome Research JO Genome Research YR 2018 FD September 01 VO 28 IS 9 SP 1309 OP 1318 DO 10.1101/gr.233809.117 UL http://genome.cshlp.org/content/28/9/1309.abstract AB The prevalence of de novo coding genes is controversial due to length and coding constraints. Noncoding genes, especially small ones, are freer to evolve de novo by comparison. The best examples are microRNAs (miRNAs), a large class of regulatory molecules ∼22 nt in length. Here, we study six de novo miRNAs in Drosophila, which, like most new genes, are testis-specific. We ask how and why de novo genes die because gene death must be sufficiently frequent to balance the many new births. By knocking out each miRNA gene, we analyzed their contributions to the nine components of male fitness (sperm production, length, and competitiveness, among others). To our surprise, the knockout mutants often perform better than the wild type in some components, and slightly worse in others. When two of the younger miRNAs are assayed in long-term laboratory populations, their total fitness contributions are found to be essentially zero. These results collectively suggest that adaptive de novo genes die regularly, not due to the loss of functionality, but due to the canceling out of positive and negative fitness effects, which may be characterized as “quasi-neutrality.” Since de novo genes often emerge adaptively and become lost later, they reveal ongoing period-specific adaptations, reminiscent of the “Red-Queen” metaphor for long-term evolution.