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  Positive and negative selection in murine ultraconserved noncoding elements

Halligan, D. L., Oliver, F., Guthrie, J., Stemshorn, K. C., Harr, B., & Keightley, P. D. (2011). Positive and negative selection in murine ultraconserved noncoding elements. Molecular Biology and Evolution, 28(9), 2651-2660. doi:10.1093/molbev/msr093.

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Halligan, Daniel L., Autor
Oliver, Fiona, Autor
Guthrie, Jack, Autor
Stemshorn, Kathryn C.1, Autor           
Harr, Bettina1, Autor           
Keightley, Peter D., Autor
Affiliations:
1Department Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445635              

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Schlagwörter: new mutations; fitness effects; conserved elements; adaptive evolution
 Zusammenfassung: There are many more selectively constrained noncoding than coding nucleotides in the mammalian genome, but most mammalian noncoding DNA is subject to weak selection, on average. One of the most striking discoveries to have emerged from comparisons among mammalian genomes is the hundreds of noncoding elements of more than 200 bp in length that show absolute conservation among mammalian orders. These elements represent the tip of the iceberg of a much larger class of conserved noncoding elements (CNEs). Much evidence suggests that CNEs are selectively constrained and not mutational cold-spots, and there is evidence that some CNEs play a role in the regulation of development. Here, we quantify negative and positive selection acting in murine CNEs by analyzing within-species nucleotide variation and between-species divergence of CNEs that we identified using a phylogenetically independent comparison. The distribution of fitness effects of new mutations in CNEs, inferred from within-species polymorphism, suggests that CNEs receive a higher number of strongly selected deleterious mutations and many fewer nearly neutral mutations than amino acid sites of protein-coding genes or regulatory elements close to genes. However, we also show that CNEs experience a far higher proportion of adaptive substitutions than any known category of genomic sites in murids. The absolute rate of adaptation of CNEs is similar to that of amino acid sites of proteins. This result suggests that there is widespread adaptation in mammalian conserved noncoding DNA elements, some of which have been implicated in the regulation of crucially important processes, including development.

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Sprache(n): eng - English
 Datum: 2011-09
 Publikationsstatus: Erschienen
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 Identifikatoren: eDoc: 572221
DOI: 10.1093/molbev/msr093
Anderer: 2869/S 39213
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Titel: Molecular Biology and Evolution
Genre der Quelle: Zeitschrift
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Seiten: - Band / Heft: 28 (9) Artikelnummer: - Start- / Endseite: 2651 - 2660 Identifikator: ISSN: 0737-4038 (print)
ISSN: 1537-1719 (online)