Letter

Nature 437, 1149-1152 (20 October 2005) | doi:10.1038/nature04107; Received 23 May 2005; Accepted 2 August 2005

Adaptive evolution of non-coding DNA in Drosophila

Peter Andolfatto1

  1. Section of Ecology, Behavior and Evolution, Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA

Correspondence to: Peter Andolfatto1 Correspondence and requests for materials should be addressed to P.A. (Email: pandolfatto@ucsd.edu).

A large fraction of eukaryotic genomes consists of DNA that is not translated into protein sequence, and little is known about its functional significance. Here I show that several classes of non-coding DNA in Drosophila are evolving considerably slower than synonymous sites, and yet show an excess of between-species divergence relative to polymorphism when compared with synonymous sites. The former is a hallmark of selective constraint, but the latter is a signature of adaptive evolution, resembling general patterns of protein evolution in Drosophila 1, 2. I estimate that about 40–70% of nucleotides in intergenic regions, untranslated portions of mature mRNAs (UTRs) and most intronic DNA are evolutionarily constrained relative to synonymous sites. However, I also use an extension to the McDonald–Kreitman test3 to show that a substantial fraction of the nucleotide divergence in these regions was driven to fixation by positive selection (about 20% for most intronic and intergenic DNA, and 60% for UTRs). On the basis of these observations, I suggest that a large fraction of the non-translated genome is functionally important and subject to both purifying selection and adaptive evolution. These results imply that, although positive selection is clearly an important facet of protein evolution, adaptive changes to non-coding DNA might have been considerably more common in the evolution of D. melanogaster.