Drosophila functional elements are embedded in structurally constrained sequences

PLoS Genet. 2013 May;9(5):e1003512. doi: 10.1371/journal.pgen.1003512. Epub 2013 May 30.


Modern functional genomics uncovered numerous functional elements in metazoan genomes. Nevertheless, only a small fraction of the typical non-exonic genome contains elements that code for function directly. On the other hand, a much larger fraction of the genome is associated with significant evolutionary constraints, suggesting that much of the non-exonic genome is weakly functional. Here we show that in flies, local (30-70 bp) conserved sequence elements that are associated with multiple regulatory functions serve as focal points to a pattern of punctuated regional increase in G/C nucleotide frequencies. We show that this pattern, which covers a region tenfold larger than the conserved elements themselves, is an evolutionary consequence of a shift in the balance between gain and loss of G/C nucleotides and that it is correlated with nucleosome occupancy across multiple classes of epigenetic state. Evidence for compensatory evolution and analysis of SNP allele frequencies show that the evolutionary regime underlying this balance shift is likely to be non-neutral. These data suggest that current gaps in our understanding of genome function and evolutionary dynamics are explicable by a model of sparse sequence elements directly encoding for function, embedded into structural sequences that help to define the local and global epigenomic context of such functional elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conserved Sequence / genetics*
  • Drosophila / genetics*
  • Evolution, Molecular*
  • Gene Frequency
  • Genetic Drift
  • Genome, Insect
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA
  • Sequence Homology, Nucleic Acid*

Grant support

Research was supported by grants from the Israeli Science Foundation (1050/12) and the European Commission MODHEP program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.