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Purifying selection maintains highly conserved noncoding sequences in Drosophila.

Sònia Casillas1, Antonio Barbadilla, Casey M Bergman

  • 1Faculty of Life Sciences, University of Manchester, Michael Smith Building, Manchester M13 9PT, UK.

Molecular Biology and Evolution
|July 25, 2007
PubMed
Summary
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Highly conserved noncoding sequences (CNSs) in Drosophila are not explained by mutation cold spots. Instead, these functional DNA regions are shaped by strong purifying selection, indicating significant biological constraint.

Area of Science:

  • Evolutionary biology
  • Genomics
  • Molecular evolution

Background:

  • Metazoan genomes contain vast nonprotein-coding regions with largely unknown functions.
  • Highly conserved noncoding sequences (CNSs) are often indicative of functional elements like cis-regulatory regions.
  • The 'mutational cold spot' hypothesis suggests CNSs may arise from low mutation rates rather than selection.

Purpose of the Study:

  • To test the mutational cold spot hypothesis for CNS evolution in Drosophila.
  • To investigate the evolutionary forces shaping CNSs using comparative genomics and population genetics.

Main Methods:

  • Comparative genomic analysis across Drosophila species.
  • Population genetic data analysis in Drosophila melanogaster.
  • Distinguishing between conserved and nonconserved DNA regions and coding sites.

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Main Results:

  • Drosophila CNSs show reduced divergence relative to polymorphism and an excess of rare alleles, consistent with purifying selection.
  • No evidence of positive selection on Drosophila CNSs, but recurrent positive selection was found in adjacent spacer regions.
  • Approximately 85% of sites in Drosophila CNSs are under strong purifying selection (selection coefficients of 10-100).

Conclusions:

  • The mutational cold spot hypothesis is incompatible with observed evolutionary patterns in Drosophila CNSs.
  • Strong purifying selection, not low mutation rates, explains the conservation of these noncoding sequences.
  • Findings suggest CNSs are unlikely to be generated by mutational cold spots in most metazoan genomes.