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The birth and death of microRNA genes in Drosophila


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.

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Figure 1: Gains of miRNA genes inferred by the parsimony method.
Figure 2: The survivorship probabilities of background (dashed line) and putative functional (red line) miRNA genes as a function of time in Myr, obtained by the maximum-likelihood method.
Figure 3: Average number of reads for newly identified miRNAs as a function of their phylogenetic distribution.

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We thank V. Ambros, G. Ruvkun, A. Clark, J. Borevitz, J. Liang, M. Long and H. Liang for helpful comments and discussion; W. Wu for statistical consultation; D. Turissini for technical assistance in database construction; and the Washington University School of Medicine Genome Sequencing Center, Agencourt Bioscience, the Broad Institute and the Drosophila Population Genomics Project for making the Drosophila genome sequence data publicly available. Y.S. and S.S. were supported by the 973 Program of China (2007CB815701). The main portion of the work was funded by the Chicago Biomedical Consortium with support from the Searle Funds at the Chicago Community Trust.

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C.-I.W., S.M.W. and R.W.C. designed this study; Q.W., S.K. and S.M.W. performed the experiments; J.L., Y.S., B.H. and S.S. did the analyses; J.L., C.-I.W. and R.W.C. contributed to the writing of this paper.

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Correspondence to San Ming Wang or Chung-I Wu.

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Lu, J., Shen, Y., Wu, Q. et al. The birth and death of microRNA genes in Drosophila. Nat Genet 40, 351–355 (2008).

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