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Microevolution of nematode miRNAs reveals diverse modes of selection.

Jovelin R, Cutter AD - Genome Biol Evol (2014)

Bottom Line: We also show that new miRNAs evolve faster than older miRNAs but that selection nevertheless favors their persistence.Moreover, we demonstrate substantial nucleotide divergence of pre-miRNA hairpin alleles between populations and sister species.These findings from the first global survey of miRNA microevolution in Caenorhabditis support the idea that changes in gene expression, mediated through divergence in miRNA regulation, can contribute to phenotypic novelty and adaptation to specific environments in the present day as well as the distant past.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Ontario, Canada richard.jovelin@utoronto.ca.

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Nonneutral pattern of sequence variation in miRNA hairpins. miRNAs with SFS deviating from neutral expectations with Tajima’s D (A) and Fay and Wu’s H (B) are labeled in orange, and miRNAs with SFS compatible with neutrality are labeled in ivory. The distributions of D and H for protein-coding genes are shown for comparison with dashed lines.
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evu239-F4: Nonneutral pattern of sequence variation in miRNA hairpins. miRNAs with SFS deviating from neutral expectations with Tajima’s D (A) and Fay and Wu’s H (B) are labeled in orange, and miRNAs with SFS compatible with neutrality are labeled in ivory. The distributions of D and H for protein-coding genes are shown for comparison with dashed lines.

Mentions: We evaluated allele frequencies within the Ohio population quantitatively using Tajima’s D (DTaj) and Fay and Wu’s H (HFW) statistics to assess skews in the SFS that can be indicative of natural selection on miRNA sequences (Tajima 1989; Fay and Wu 2000). We detected nonneutral patterns of nucleotide variation in nine genes, four of which have an SNP located in the mature miR (mir-35b, mir-248, mir-787, and mir-2227). SNPs in seven miRNAs show an excess of rare variants (DTaj < 0 for mir-35b, mir-248, mir-356, mir-784, mir-787, mir-2227, and mir-2230; fig. 4A) and three miRNAs have an excess of derived high-frequency alleles (HFW < 0 for mir-64c, mir-248, and block2005; fig. 4B). These tests are significant only for mir-248 and mir-35b after applying the Benjamini–Hochberg correction for multiple testing with a 5% false discovery rate. Note that the miRNAs with nonneutral patterns of diversity identified with the DTaj and the HFW statistics are largely nonoverlapping because of the lack of an available orthologous outgroup for most of the miRNAs with significant skewed SFS. Nevertheless, this discrepancy could also reflect differences between the two tests because negative DTaj values are compatible with the action of negative and positive selection, whereas negative HFW values typically indicate positive selection. Six of these eight miRNAs with nonneutral patterns of variation have homologs in C. elegans. To gain insights into the potential function of these six miRNAs, we obtained the lists of all predicted target genes in C. elegans using TargetScanWorm 6.2 (Jan et al. 2011), and determined functional enrichment of Gene Ontology (GO) terms related to biological processes using DAVID (Huang et al. 2009). Interestingly, the first ranked functional clusters of five miRNAs (mir-64, mir-248, mir-356, mir-784, and mir-787) are enriched for GO terms related to gonad development, although enrichment is significant only for mir-248, mir-356, and mir-787 after correction for multiple testing (supplementary table S5, Supplementary Material online). The SFS for SNPs in flanking regions of mir-248, mir-784, and mir-2230 also deviate from neutrality, so we could not precisely identify the genomic loci with perturbed SFS. Nevertheless, nongenic regions of these miRNAs (supplementary fig. S3, Supplementary Material online) could contain cis-regulatory sites affecting miRNA transcription, which also may represent important targets of selection.Fig. 4.—


Microevolution of nematode miRNAs reveals diverse modes of selection.

Jovelin R, Cutter AD - Genome Biol Evol (2014)

Nonneutral pattern of sequence variation in miRNA hairpins. miRNAs with SFS deviating from neutral expectations with Tajima’s D (A) and Fay and Wu’s H (B) are labeled in orange, and miRNAs with SFS compatible with neutrality are labeled in ivory. The distributions of D and H for protein-coding genes are shown for comparison with dashed lines.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255771&req=5

evu239-F4: Nonneutral pattern of sequence variation in miRNA hairpins. miRNAs with SFS deviating from neutral expectations with Tajima’s D (A) and Fay and Wu’s H (B) are labeled in orange, and miRNAs with SFS compatible with neutrality are labeled in ivory. The distributions of D and H for protein-coding genes are shown for comparison with dashed lines.
Mentions: We evaluated allele frequencies within the Ohio population quantitatively using Tajima’s D (DTaj) and Fay and Wu’s H (HFW) statistics to assess skews in the SFS that can be indicative of natural selection on miRNA sequences (Tajima 1989; Fay and Wu 2000). We detected nonneutral patterns of nucleotide variation in nine genes, four of which have an SNP located in the mature miR (mir-35b, mir-248, mir-787, and mir-2227). SNPs in seven miRNAs show an excess of rare variants (DTaj < 0 for mir-35b, mir-248, mir-356, mir-784, mir-787, mir-2227, and mir-2230; fig. 4A) and three miRNAs have an excess of derived high-frequency alleles (HFW < 0 for mir-64c, mir-248, and block2005; fig. 4B). These tests are significant only for mir-248 and mir-35b after applying the Benjamini–Hochberg correction for multiple testing with a 5% false discovery rate. Note that the miRNAs with nonneutral patterns of diversity identified with the DTaj and the HFW statistics are largely nonoverlapping because of the lack of an available orthologous outgroup for most of the miRNAs with significant skewed SFS. Nevertheless, this discrepancy could also reflect differences between the two tests because negative DTaj values are compatible with the action of negative and positive selection, whereas negative HFW values typically indicate positive selection. Six of these eight miRNAs with nonneutral patterns of variation have homologs in C. elegans. To gain insights into the potential function of these six miRNAs, we obtained the lists of all predicted target genes in C. elegans using TargetScanWorm 6.2 (Jan et al. 2011), and determined functional enrichment of Gene Ontology (GO) terms related to biological processes using DAVID (Huang et al. 2009). Interestingly, the first ranked functional clusters of five miRNAs (mir-64, mir-248, mir-356, mir-784, and mir-787) are enriched for GO terms related to gonad development, although enrichment is significant only for mir-248, mir-356, and mir-787 after correction for multiple testing (supplementary table S5, Supplementary Material online). The SFS for SNPs in flanking regions of mir-248, mir-784, and mir-2230 also deviate from neutrality, so we could not precisely identify the genomic loci with perturbed SFS. Nevertheless, nongenic regions of these miRNAs (supplementary fig. S3, Supplementary Material online) could contain cis-regulatory sites affecting miRNA transcription, which also may represent important targets of selection.Fig. 4.—

Bottom Line: We also show that new miRNAs evolve faster than older miRNAs but that selection nevertheless favors their persistence.Moreover, we demonstrate substantial nucleotide divergence of pre-miRNA hairpin alleles between populations and sister species.These findings from the first global survey of miRNA microevolution in Caenorhabditis support the idea that changes in gene expression, mediated through divergence in miRNA regulation, can contribute to phenotypic novelty and adaptation to specific environments in the present day as well as the distant past.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Ontario, Canada richard.jovelin@utoronto.ca.

Show MeSH
Related in: MedlinePlus