Local Packing Density Is the Main Structural Determinant of the Rate of Protein Sequence Evolution at Site Level

• Autores: Yeh, So Wei; Huang, Tsun Tsao; Liu, Jen Wei; Yu, Sung Huan; Shih, Chien Hua; Hwang, Jenn Kang; Echave, Julian
• Año de publicación: 2014
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Protein; Evolution
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Functional and biophysical constraints result in site-dependent patterns of protein sequence variability. It is commonly assumed that the key structural determinant of site-specific rates of evolution is the Relative Solvent Accessibility (RSA). However, a recent study found that amino acid substitution rates correlate better with two Local Packing Density (LPD) measures, the Weighted Contact Number (WCN) and the Contact Number (CN), than with RSA. This work aims at a more thorough assessment. To this end, in addition to substitution rates, we considered four other sequence variability scores, four measures of solvent accessibility (SA), and other CN measures. We compared all properties for each protein of a structurally and functionally diverse representative dataset of monomeric enzymes. We show that the best sequence variability measures take into account phylogenetic tree topology. More importantly, we show that both LPD measures (WCN and CN) correlate better than all of the SA measures, regardless of the sequence variability score used. Moreover, the independent contribution of the best LPD measure is approximately four times larger than that of the best SA measure. This study strongly supports the conclusion that a site’s packing density rather than its solvent accessibility is the main structural determinant of its rate of evolution.
Fil: Yeh, So Wei. National Chiao Tung University; China
Fil: Huang, Tsun Tsao. National Chiao Tung University; China
Fil: Liu, Jen Wei. National Chiao Tung University; China
Fil: Yu, Sung Huan. National Chiao Tung University; China
Fil: Shih, Chien Hua. National Chiao Tung University; China
Fil: Hwang, Jenn Kang. National Chiao Tung University; China
Fil: Echave, Julian. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina