Systematic variation of amino acid substitutions for stringent assessment of pairwise covariation.

@article{citeulike:2047047, abstract = {During protein evolution, amino acids change due to a combination of functional constraints and genetic drift. Proteins frequently contain pairs of amino acids that appear to change together (covariation). Analysis of covariation from naturally occurring sets of orthologs cannot distinguish between residue pairs retained by functional requirements of the protein and those pairs existing due to changes along a common evolutionary path. Here, we have separated the two types of covariation by independently recombining every naturally occurring amino acid variant within a set of 15 subtilisin orthologs. Our analysis shows that in this family of subtilisin orthologs, almost all possible pairwise combinations of amino acids can coexist. This suggests that amino acid covariation found in the subtilisin orthologs is almost entirely due to common ancestral origin of the changes rather than functional constraints. We conclude that naturally occurring sequence diversity can be used to identify positions that can vary independently without destroying protein function.}, address = {Maxygen Inc., 200 Penebscot Drive, Redwood City, CA 94063, USA. sgovindarajan@dnatwopointo.com}, author = {Govindarajan, S. and Ness, J. E. and Kim, S. and Mundorff, E. C. and Minshull, J. and Gustafsson, C. }, citeulike-article-id = {2047047}, issn = {0022-2836}, journal = {J Mol Biol}, keywords = {coevolution, correlated-mutation}, month = {May}, number = {5}, pages = {1061--1069}, posted-at = {2007-12-03 02:39:36}, priority = {2}, title = {Systematic variation of amino acid substitutions for stringent assessment of pairwise covariation.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12729741}, volume = {328}, year = {2003} }

TY - JOUR ID - citeulike:2047047 L3 - citeulike-article-id:2047047 TI - Systematic variation of amino acid substitutions for stringent assessment of pairwise covariation. JF - J Mol Biol VL - 328 IS - 5 SP - 1061 EP - 1069 AD - Maxygen Inc., 200 Penebscot Drive, Redwood City, CA 94063, USA. sgovindarajan@dnatwopointo.com SN - 0022-2836 N2 - During protein evolution, amino acids change due to a combination of functional constraints and genetic drift. Proteins frequently contain pairs of amino acids that appear to change together (covariation). Analysis of covariation from naturally occurring sets of orthologs cannot distinguish between residue pairs retained by functional requirements of the protein and those pairs existing due to changes along a common evolutionary path. Here, we have separated the two types of covariation by independently recombining every naturally occurring amino acid variant within a set of 15 subtilisin orthologs. Our analysis shows that in this family of subtilisin orthologs, almost all possible pairwise combinations of amino acids can coexist. This suggests that amino acid covariation found in the subtilisin orthologs is almost entirely due to common ancestral origin of the changes rather than functional constraints. We conclude that naturally occurring sequence diversity can be used to identify positions that can vary independently without destroying protein function. KW - coevolution KW - correlated-mutation AU - Govindarajan, S AU - Ness, JE AU - Kim, S AU - Mundorff, EC AU - Minshull, J AU - Gustafsson, C PY - 2003/05/16/ UR - http://view.ncbi.nlm.nih.gov/pubmed/12729741 ER -