Natural selection of protein structural and functional properties: a SNP perspective

@article{citeulike:2642559, abstract = {BACKGROUND:The rates of molecular evolution for protein-coding genes depend on the stringency of functional or structural constraints. The Ka/Ks ratio has been commonly used as an indicator of selective constraints and is typically calculated from interspecies alignments. Recent accumulation of single nucleotide polymorphism data has enabled the derivation of Ka/Ks for polymorphism (SNP A/S ratio).RESULTS:Using data from dbSNP, we conducted the first large-scale survey of SNP A/S ratios for different structural and functional properties. We confirmed that the SNP A/S ratio is largely correlated with Ka/Ks for divergence. We observed stronger selective constraints for proteins that have high mRNA expression level or broad expression patterns, have no paralogs, arise earlier in evolution, have natively disordered region, are located in cytoplasm and nucleus, or are related to human diseases. On the residue level, we found higher degree of variation for residues that are exposed to solvent, are in loop conformation, natively disordered regions or low complexity regions, or are in the signal peptides of secreted proteins. Our analysis also revealed that histones and protein kinases are among the protein families that are under the strongest selective constraints, whereas olfactory and taste receptors are among the most variable groups.CONCLUSIONS:Our study suggests that the SNP A/S ratio is a robust measure for selective constraints. The correlations between SNP A/S ratios and other variables provide valuable insights into the natural selection of various structural or functional properties, particularly for human-specific genes and constraints within the human lineage.}, author = {Liu, Jinfeng and Zhang, Yan and Lei, Xingye and Zhang, Zemin }, citeulike-article-id = {2642559}, doi = {10.1186/gb-2008-9-4-r69}, journal = {Genome Biology}, keywords = {molecular\_evolution, natural\_selection, polymorphism, snp}, number = {4}, posted-at = {2008-04-09 00:01:16}, priority = {2}, title = {Natural selection of protein structural and functional properties: a SNP perspective}, url = {http://dx.doi.org/10.1186/gb-2008-9-4-r69}, volume = {9}, year = {2008} }

TY - JOUR ID - citeulike:2642559 L3 - citeulike-article-id:2642559 TI - Natural selection of protein structural and functional properties: a SNP perspective JF - Genome Biology VL - 9 IS - 4 N2 - BACKGROUND:The rates of molecular evolution for protein-coding genes depend on the stringency of functional or structural constraints. The Ka/Ks ratio has been commonly used as an indicator of selective constraints and is typically calculated from interspecies alignments. Recent accumulation of single nucleotide polymorphism data has enabled the derivation of Ka/Ks for polymorphism (SNP A/S ratio).RESULTS:Using data from dbSNP, we conducted the first large-scale survey of SNP A/S ratios for different structural and functional properties. We confirmed that the SNP A/S ratio is largely correlated with Ka/Ks for divergence. We observed stronger selective constraints for proteins that have high mRNA expression level or broad expression patterns, have no paralogs, arise earlier in evolution, have natively disordered region, are located in cytoplasm and nucleus, or are related to human diseases. On the residue level, we found higher degree of variation for residues that are exposed to solvent, are in loop conformation, natively disordered regions or low complexity regions, or are in the signal peptides of secreted proteins. Our analysis also revealed that histones and protein kinases are among the protein families that are under the strongest selective constraints, whereas olfactory and taste receptors are among the most variable groups.CONCLUSIONS:Our study suggests that the SNP A/S ratio is a robust measure for selective constraints. The correlations between SNP A/S ratios and other variables provide valuable insights into the natural selection of various structural or functional properties, particularly for human-specific genes and constraints within the human lineage. KW - molecular_evolution KW - natural_selection KW - polymorphism KW - snp AU - Liu, Jinfeng AU - Zhang, Yan AU - Lei, Xingye AU - Zhang, Zemin PY - 2008/// UR - http://dx.doi.org/10.1186/gb-2008-9-4-r69 ER -