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An Integrated Approach for Microprotein Identification and Sequence Analysis
09:37

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Published on: July 12, 2022

Positive and negative selection in murine ultraconserved noncoding elements.

Daniel L Halligan1, Fiona Oliver, Jack Guthrie

  • 1Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.

Molecular Biology and Evolution
|April 12, 2011
PubMed
Summary

Conserved noncoding elements (CNEs) in mouse genomes show high rates of adaptation, suggesting widespread evolutionary innovation in non-coding DNA. These elements are crucial for development and exhibit unique selection patterns compared to protein-coding genes.

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Mammalian genomes contain numerous selectively constrained noncoding nucleotides, with hundreds of conserved noncoding elements (CNEs) over 200 bp identified across mammalian orders.
  • Evidence suggests CNEs are under selective constraint and play roles in developmental regulation, not merely mutational cold spots.

Purpose of the Study:

  • To quantify negative and positive selection acting on murine CNEs.
  • To compare selection pressures on CNEs with protein-coding genes and other regulatory elements.

Main Methods:

  • Analysis of within-species nucleotide variation and between-species divergence of murine CNEs.
  • Identification of CNEs using a phylogenetically independent comparison.

Main Results:

  • CNEs experience a higher load of strongly selected deleterious mutations and fewer nearly neutral mutations than protein-coding sites.
  • CNEs exhibit a significantly higher proportion of adaptive substitutions compared to other genomic sites in murids.
  • The rate of adaptation in CNEs is comparable to that of amino acid sites in proteins.

Conclusions:

  • Mammalian conserved noncoding DNA demonstrates widespread adaptation.
  • CNEs are key sites for evolutionary innovation, with implications for understanding the regulation of critical biological processes like development.