Project description:MicroRNAs (miRNAs) are small, endogenously expressed RNAs that regulate mRNAs post-transcriptionally. The class of miRNA genes, like other gene classes, should experience birth, death and persistence of its members. We carried out deep sequencing of miRNAs from three species of Drosophila, and obtained 107,000 sequences that map to no fewer than 300 loci that were not previously known. We observe a large class of miRNA genes that are evolutionarily young, with a rate of birth of 12 new genes per million years (Myr). Most of these new miRNAs originated from non-miRNA sequences. Among the new genes, we estimate that 96% disappeared quickly in the course of evolution; only 4% of new miRNA genes were retained by natural selection. Furthermore, only 60% of these retained genes became integrated into the transcriptome in the long run (60 Myr). This small fraction (2.5%) of surviving miRNAs may later on become moderately or highly expressed. Our results suggest that there is a high birth rate of new miRNA genes, accompanied by a comparably high death rate. The estimated net gain of long-lived miRNA genes, which is not strongly affected by either the depth or the breadth (number of tissues) of sequencing, is 0.3 genes per Myr in Drosophila Keywords: 454 microRNA deep sequencing
Project description:MicroRNAs (miRNAs) are small, endogenously expressed RNAs that regulate mRNAs post-transcriptionally. The class of miRNA genes, like other gene classes, should experience birth, death and persistence of its members. We carried out deep sequencing of miRNAs from three species of Drosophila, and obtained 107,000 sequences that map to no fewer than 300 loci that were not previously known. We observe a large class of miRNA genes that are evolutionarily young, with a rate of birth of 12 new genes per million years (Myr). Most of these new miRNAs originated from non-miRNA sequences. Among the new genes, we estimate that 96% disappeared quickly in the course of evolution; only 4% of new miRNA genes were retained by natural selection. Furthermore, only 60% of these retained genes became integrated into the transcriptome in the long run (60 Myr). This small fraction (2.5%) of surviving miRNAs may later on become moderately or highly expressed. Our results suggest that there is a high birth rate of new miRNA genes, accompanied by a comparably high death rate. The estimated net gain of long-lived miRNA genes, which is not strongly affected by either the depth or the breadth (number of tissues) of sequencing, is 0.3 genes per Myr in Drosophila Keywords: 454 microRNA deep sequencing Three small RNA samples from male heads of D. melanogaster, D. simulans and D. pseudoobscura were analyzed. The small RNAs were sequenced by 454 technology. After removing the flank adaptor sequences, the inserted sequences greater than 18nt were extracted.
Project description: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.
Project description:Here we analyze the molecular evolution of the beta-esterase gene cluster in the Drosophila genus using the recently released genome sequences of 12 Drosophila species. Molecular evolution in this small cluster is noteworthy because it contains contrasting examples of the types and stages of loss of gene function. Specifically, missing orthologs, pseudogenes, and null alleles are all inferred. Phylogenetic analyses also suggest a minimum of 9 gene gain-loss events; however, the exact number and age of these events is confounded by interparalog recombination. A previous enigma, in which allozyme loci were mapped to beta-esterase genes that lacked catalytically essential amino acids, was resolved through the identification of neighbouring genes that contain the canonical catalytic residues and thus presumably encode the mapped allozymes. The originally identified genes are evolving with selective constraint, suggesting that they have a "noncatalytic" function. Curiously, 3 of the 4 paralogous beta-esterase genes in the D. ananassae genome sequence have single inactivating (frame-shift or nonsense) mutations. To determine whether these putatively inactivating mutations were fixed, we sequenced other D. ananassae alleles of these four loci. We did not find any of the 3 inactivating mutations of the sequenced strain in 12 other strains; however, other inactivating mutations were observed in the same 3 genes. This is reminiscent of the high frequency of null alleles observed in one of the beta-esterase genes (Est7/EstP) of D. melanogaster.
Project description:Preterm birth, defined as birth <37 weeks of gestation, is a leading cause of infant morbidity and mortality. In the United States, approximately 12% of all births are preterm.1 Despite decades of research, there has been little progress in developing effective interventions to prevent preterm birth. In fact, the rate of preterm birth has increased slightly over the last several decades.2 The ultimate goal of the Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR) is to identify possible biomarkers that could predict the susceptibility to spontaneous preterm birth (SPTB) as well as to shed light on the molecular mechanisms involved in its etiologies. Understanding those mechanisms will help us predict SPTB and may facilitate the introduction of more effective prevention and treatment strategies.