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Regulatory changes underlying expression differences within and between Drosophila species.

Patricia J Wittkopp1, Belinda K Haerum, Andrew G Clark

  • 1Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA. wittkopp@umich.edu

Nature Genetics
|February 19, 2008
PubMed
Summary
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Natural selection favors cis-regulatory changes over trans-regulatory changes in gene expression, particularly between species. This suggests evolutionary pressures shape the mechanisms driving genetic variation.

Area of Science:

  • Evolutionary genetics
  • Molecular evolution
  • Genomics

Background:

  • Gene expression differences contribute to phenotypic variation.
  • Changes in cis- and trans-regulation are key drivers of gene expression variation.
  • Cis-regulatory variants affect allele-specific expression, while trans-regulatory variants affect both alleles.

Purpose of the Study:

  • To investigate the contributions of cis- and trans-regulatory changes to gene expression variation.
  • To determine if natural selection favors one type of regulatory change over the other.

Main Methods:

  • Analyzed gene expression in four strains of Drosophila melanogaster and three strains of D. simulans.
  • Examined the role of cis- and trans-regulatory changes in 78 genes.
  • Compared intra- and interspecific gene expression differences.

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Main Results:

  • Cis-regulatory changes account for a larger proportion of expression differences between species than within species.
  • Data contradicts a neutral model where cis- and trans-regulatory polymorphisms have equal fixation probabilities.
  • Evidence suggests natural selection influences the molecular mechanisms of divergent gene expression.

Conclusions:

  • Natural selection appears to preferentially accumulate cis-regulatory changes over time.
  • Evolutionary pressures shape the mechanisms underlying gene expression divergence.
  • Cis-regulatory evolution plays a significant role in species differentiation.