Nature 448, 587-590 (2 August 2007) | doi:10.1038/nature05988; Received 16 November 2006; Accepted 5 June 2007; Published online 15 July 2007

Morphological evolution through multiple cis-regulatory mutations at a single gene

Alistair P. McGregor1,3, Virginie Orgogozo1,3, Isabelle Delon2,3, Jennifer Zanet2, Dayalan G. Srinivasan1, François Payre2 & David L. Stern1

  1. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA
  2. Centre de Biologie du Développement, Bâtiment 4R3, 118 Route de Narbonne, 31062 cedex 4 Toulouse, France
  3. Present addresses: Institute for Genetics, University of Cologne, D-50674, Cologne, Germany (A.P.McG.); Université Pierre et Marie Curie, Bâtiment A, 7 Quai Saint Bernard, 75005 Paris, France (V.O.); The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 1QN, UK (I.D.).

Correspondence to: David L. Stern1 Correspondence and requests for materials should be addressed to D.L.S. (Email: dstern@princeton.edu).

One central, and yet unsolved, question in evolutionary biology is the relationship between the genetic variants segregating within species and the causes of morphological differences between species. The classic neo-darwinian view postulates that species differences result from the accumulation of small-effect changes at multiple loci. However, many examples support the possible role of larger abrupt changes in the expression of developmental genes in morphological evolution1, 2, 3. Although this evidence might be considered a challenge to a neo-darwinian micromutationist view of evolution, there are currently few examples of the actual genes causing morphological differences between species4, 5, 6, 7, 8, 9, 10. Here we examine the genetic basis of a trichome pattern difference between Drosophila species, previously shown to result from the evolution of a single gene, shavenbaby (svb), probably through cis-regulatory changes6. We first identified three distinct svb enhancers from D. melanogaster driving reporter gene expression in partly overlapping patterns that together recapitulate endogenous svb expression. All three homologous enhancers from D. sechellia drive expression in modified patterns, in a direction consistent with the evolved svb expression pattern. To test the influence of these enhancers on the actual phenotypic difference, we conducted interspecific genetic mapping at a resolution sufficient to recover multiple intragenic recombinants. This functional analysis revealed that independent genetic regions upstream of svb that overlap the three identified enhancers are collectively required to generate the D. sechellia trichome pattern. Our results demonstrate that the accumulation of multiple small-effect changes at a single locus underlies the evolution of a morphological difference between species. These data support the view that alleles of large effect that distinguish species may sometimes reflect the accumulation of multiple mutations of small effect at select genes.


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