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

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

On the possibility of death of new genes – evidence from the deletion of de novo microRNAs

Abstract Background New genes are constantly formed, sometimes from non-genic sequences, creating what is referred to as de novo genes. Since the total number of genes remains relatively steady, gene deaths likely balance out new births. In metazoan genomes, microRNAs (miRs) genes, small and non-coding, account for the bulk of functional de novo genes and are particularly suited to the investigation of gene death. Results In this study, we discover a Drosophila-specific de novo miRNA (mir-977) that may be facing impending death. Strikingly, after this testis-specific gene is deleted from D. melanogaster, most components of male fitness increase, rather than decrease as had been expected. These components include male viability, fertility and males’ ability to repress female re-mating. Given that mir-977 has a negative fitness effect in D. melanogaster, this de novo gene with an adaptive history for over 60 Myrs may be facing elimination. In some other species where mir-977 is not found, gene death may have already happened. Conclusion The surprising result suggests that de novo genes, constantly rising and falling during evolution, may often be transiently adaptive and then purged from the genome

Additional file 1: of On the possibility of death of new genes – evidence from the deletion of de novo microRNAs

Figure S1. Independent deletion confirms male fertility increase due to mir-977 deletion. Figure S2. Lifecycle of new gene. Table S1. mir-977 expression in Drosophila species. Table S2. Expression variation of mir-977 in testes across 5 lines of D. melanogaster. Table S3. Male fertility of mir-977 KO. Table S4. Stimulating ovulation and sperm quality of mir-977 KO. Table S5. Meiotic drive of mir-977 KO. Table S6. Viability of mir-977 KO. Table S7. Mating success of mir-977 KO. Table S8. Primers used in this study. Table S9. TALEN pairs design for mir-977. (PPTX 277 kb

Additional file 3: of On the possibility of death of new genes – evidence from the deletion of de novo microRNAs

Raw data of male fitness components for mir-977 KO. Detail components: male fertility (related to Fig. 3a and Additional file 1: Figure S1b), stimulating ovulation (related to Fig. 3a), sperm quality (related to Fig. 3a), meiotic drive (related to Fig. 3b). (XLSX 12 kb

Additional file 2: of On the possibility of death of new genes – evidence from the deletion of de novo microRNAs

Supplementary Text 1.The choice of genetic background. Supplementary Text 2. Discussion about the off-target effect. Supplementary Text 3. Possible mechanism of mir-977’s phenotypic effect. (PDF 414 kb

Canalization of Phenotypes-When the Transcriptome is Constantly but Weakly Perturbed

Recent studies have increasingly pointed to microRNAs (miRNAs) as the agent of gene regulatory network (GRN) stabilization as well as developmental canalization against constant but small environmental perturbations. To analyze mild perturbations, we construct a Dicer-1 knockdown line (dcr-1 KD) in Drosophila that modestly reduces all miRNAs by, on average, ∼20%. The defining characteristic of stabilizers is that, when their capacity is compromised, GRNs do not change their short-term behaviors. Indeed, even with such broad reductions across all miRNAs, the changes in the transcriptome are very modest during development in stable environment. By comparison, broad knockdowns of other regulatory genes (esp. transcription factors) by the same method should lead to drastic changes in the GRNs. The consequence of destabilization may thus be in long-term development as postulated by the theory of canalization. Flies with modest miRNA reductions may gradually deviate from the developmental norm, resulting in late-stage failures such as shortened longevity. In the optimal culture condition, the survival to adulthood is indeed normal in the dcr-1 KD line but, importantly, adult longevity is reduced by ∼90%. When flies are stressed by high temperature, dcr-1 KD induces lethality earlier in late pupation and, as the perturbations are shifted earlier, the affected stages are shifted correspondingly. Hence, in late stages of development with deviations piling up, GRN would be increasingly in need of stabilization. In conclusion, miRNAs appear to be a solution to weak but constant environmental perturbations