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Assessing constraints on the path of regulatory sequence evolution.

William J Glassford1, Mark Rebeiz

  • 1Department of Biological Sciences, University of Pittsburgh, , 4249 Fifth Avenue, Pittsburgh, PA 15260, USA.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|November 13, 2013
PubMed
Summary

Evolutionary paths of enhancers are guided by constraints. Studying the Neprilysin-1 (Nep1) gene in Drosophila revealed how mutations shape enhancer activity, highlighting epistatic and cooperative effects.

Keywords:
cis-regulatory evolutionmutational pathpleiotropysign epistasis

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Area of Science:

  • Evolutionary biology
  • Genetics
  • Molecular biology

Background:

  • Protein evolution is constrained, but constraints on regulatory sequences like enhancers are less understood.
  • The Neprilysin-1 (Nep1) gene in Drosophila offers a model to study enhancer evolution.
  • Drosophila santomea shows a novel optic lobe expression pattern for Nep1, evolved from its ancestor.

Purpose of the Study:

  • Investigate evolutionary constraints on transcriptional regulatory sequences (enhancers).
  • Elucidate the evolutionary path of a novel enhancer activity in the Drosophila optic lobe.
  • Understand how mutations shape enhancer function and evolutionary trajectories.

Main Methods:

  • Recreating and testing ancestral enhancer sequences in Drosophila.
  • Analyzing all possible intermediate evolutionary steps between ancestral and modern enhancers.
  • Observing transcriptional output to identify epistatic and cooperative effects.

Main Results:

  • The modern Drosophila santomea optic lobe enhancer evolved from a weak ancestral activity.
  • Each fixed mutation contributed to the novel enhancer activity.
  • Many evolutionary paths exhibited epistasis and cooperation.
  • Some paths led to increased ectopic activity or affected pre-existing enhancer functions.

Conclusions:

  • Evolutionary paths of enhancers are constrained by various factors.
  • Epistatic and cooperative effects significantly influence enhancer evolution.
  • Constraints can guide the emergence of novel gene expression patterns through enhancer co-option.