Adaptive evolution of non-coding DNA in Drosophila. Author Peter Andolfatto Publication Year 2005 Type Journal Article Abstract 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. 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 test 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. Keywords Animals, Drosophila, Models, Genetic, Evolution, Molecular, Drosophila melanogaster, Genomics, Introns, Polymorphism, Genetic, Selection, Genetic, Adaptation, Physiological, Nucleotides, Mutagenesis, DNA, Intergenic, Untranslated Regions, Zimbabwe Journal Nature Volume 437 Issue 7062 Pages 1149-52 Date Published 10/2005 Alternate Journal Nature Google ScholarBibTeXEndNote X3 XML