title: DNA indels in coding regions reveal selective constraints on protein evolution in the human lineage.
abstract: BACKGROUND
  Insertions and deletions of DNA segments (indels) are together with substitutions the major mutational processes that generate genetic variation. Here we focus on recent DNA insertions and deletions in protein coding regions of the human genome to investigate selective constraints on indels in protein evolution.
  
  
  RESULTS
  Frequencies of inserted and deleted amino acids differ from background amino acid frequencies in the human proteome. Small amino acids are overrepresented, while hydrophobic, aliphatic and aromatic amino acids are strongly suppressed. Indels are found to be preferentially located in protein regions that do not form important structural domains. Amino acid insertion and deletion rates in genes associated with elementary biochemical reactions (e. g. catalytic activity, ligase activity, electron transport, or catabolic process) are lower compared to those in other genes and are therefore subject to stronger purifying selection.
  
  
  CONCLUSIONS
  Our analysis indicates that indels in human protein coding regions are subject to distinct levels of selective pressure with regard to their structural impact on the amino acid sequence, as well as to general properties of the genes they are located in. These findings confirm that many commonly accepted characteristics of selective constraints for substitutions are also valid for amino acid insertions and deletions.
authors.affiliation: Department for Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, Ihnestr, 63-73, 14195 Berlin, Germany. n.delachaux@bioc.unizh.ch
authors.forename: Nicole
authors.initials: N
authors.lastname: de la Chaux
authors.forename: Philipp W
authors.initials: PW
authors.lastname: Messer
authors.forename: Peter F
authors.initials: PF
authors.lastname: Arndt