title: Tertiary windowing to detect positive diversifying selection.
abstract: As a protein-encoding gene evolves, different selective pressures act on the gene temporally and spatially. An examination of the ratio of nonsynonymous-to-synonymous nucleotide substitution rate ratios (K(a)/K(s)) has proven to be a valuable method to examine selective pressures on protein encoding genes, including detecting positive diversifying selection. To gain power over averaging all sites in a gene together, examination of sites in primary sequence windows has frequently been employed. However, selection acts on folded proteins and sites that are close in tertiary space may not be close in primary sequence. A new method for the examination of K(a)/K(s) ratios based upon windows in tertiary structure is introduced and applied to the leptin gene family in mammals. Tertiary sequence windowing detects new sites under positive diversifying selection and detects positive diversifying selection with a more significant signal along various branches of the leptin gene family tree.
authors.affiliation: Computational Biology Unit, BCCS, University of Bergen, 5020, Bergen, Norway.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Berglund
authors.forename: Björn
authors.initials: B
authors.lastname: Wallner
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
authors.forename: David A
authors.initials: DA
authors.lastname: Liberles
mesh_terms: D000818:Animals; D008958:Models, Molecular; D011323:Primates; D011487:Protein Conformation; D012641:Selection, Genetic