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Neighbor preferences of amino acids and context-dependent effects of amino acid substitutions in human, mouse, and dog.

Fu M, Huang Z, Mao Y, Tao S - Int J Mol Sci (2014)

Bottom Line: Our results showed that nearly half of 380 substitution types were evidently context dependent, and the context-dependent patterns relied on protein secondary structures.Among 20 amino acids, P elicited the greatest effect on amino acid substitutions.The underlying mechanisms of context-dependent effects of amino acid substitutions were possibly mutation bias at a DNA level and natural selection.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences and State Key Laboratory of Crop Stress Biology in Arid Areas, Northwest A&F University, Yangling 712100, China. fmcsky@nwsuaf.edu.cn.

ABSTRACT
Amino acids show apparent propensities toward their neighbors. In addition to preferences of amino acids for their neighborhood context, amino acid substitutions are also considered to be context-dependent. However, context-dependence patterns of amino acid substitutions still remain poorly understood. Using relative entropy, we investigated the neighbor preferences of 20 amino acids and the context-dependent effects of amino acid substitutions with protein sequences in human, mouse, and dog. For 20 amino acids, the highest relative entropy was mostly observed at the nearest adjacent site of either N- or C-terminus except C and G. C showed the highest relative entropy at the third flanking site and periodic pattern was detected at G flanking sites. Furthermore, neighbor preference patterns of amino acids varied greatly in different secondary structures. We then comprehensively investigated the context-dependent effects of amino acid substitutions. Our results showed that nearly half of 380 substitution types were evidently context dependent, and the context-dependent patterns relied on protein secondary structures. Among 20 amino acids, P elicited the greatest effect on amino acid substitutions. The underlying mechanisms of context-dependent effects of amino acid substitutions were possibly mutation bias at a DNA level and natural selection. Our findings may improve secondary structure prediction algorithms and protein design; moreover, this study provided useful information to develop empirical models of protein evolution that consider dependence between residues.

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Related in: MedlinePlus

Neighbor preference pattern of the amino acid C. (A) Relative entropies of the neighboring sites of C of N- and C-termini; (B) Boxplot of the 20 relative entropies at each flanking site of the amino acid C.
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ijms-15-15963-f002: Neighbor preference pattern of the amino acid C. (A) Relative entropies of the neighboring sites of C of N- and C-termini; (B) Boxplot of the 20 relative entropies at each flanking site of the amino acid C.

Mentions: We initially assessed the neighbor preference pattern of each amino acid type. Our results showed that all of the 20 amino acids were remarkably neighbor-preferred (Figure S1). The highest relative entropy was mainly observed at the nearest adjacent site of either N- or C-terminus, indicating that neighbor preferences were the strongest for the two immediate flanking sites; this value subsequently decreased when the distance to the 0 site increased. Relative entropy decreased rapidly in the nearest 5 to 7 flanking sites; afterward, relative entropy decreased very slowly and became not significant (Figure 1A). C and G are two exceptions. For C (Figure 2A), the highest relative entropies appeared at the third flanking sites of both N- and C-termini. Without these sites, relative entropies were relatively low. For G (Figure 3A), the relative entropies of N- and C-terminal flanking sites showed an evident periodic change, that is, relative entropies were remarkably high in all of the 3n (n = ±1, ±2, ±3…) flanking sites; other sites showed low values. The peaks at the 3n flanking sites decreased gradually when the distance to the 0 site increased. To determine the specific amino acids responsible for the high relative entropy at one flanking site, we further investigated the 20 relative entropies calculated using at each flanking site of the 20 amino acids (Figure 1B, Figure 2B, and Figure 3B). We found that for more than half of the amino acids (A, L, V, P, G, S, T, Q, C, H, K, R, D, and E), the corresponding residues tended to show high propensity at the neighboring sites (e.g., in Figure 1B, amino acid A was a outlier which was above the upper whisker of the boxplot in each flanking site, which demonstrated that amino acid A was a type of preferred amino acid in the neighboring sites of amino acid A).


Neighbor preferences of amino acids and context-dependent effects of amino acid substitutions in human, mouse, and dog.

Fu M, Huang Z, Mao Y, Tao S - Int J Mol Sci (2014)

Neighbor preference pattern of the amino acid C. (A) Relative entropies of the neighboring sites of C of N- and C-termini; (B) Boxplot of the 20 relative entropies at each flanking site of the amino acid C.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4200849&req=5

ijms-15-15963-f002: Neighbor preference pattern of the amino acid C. (A) Relative entropies of the neighboring sites of C of N- and C-termini; (B) Boxplot of the 20 relative entropies at each flanking site of the amino acid C.
Mentions: We initially assessed the neighbor preference pattern of each amino acid type. Our results showed that all of the 20 amino acids were remarkably neighbor-preferred (Figure S1). The highest relative entropy was mainly observed at the nearest adjacent site of either N- or C-terminus, indicating that neighbor preferences were the strongest for the two immediate flanking sites; this value subsequently decreased when the distance to the 0 site increased. Relative entropy decreased rapidly in the nearest 5 to 7 flanking sites; afterward, relative entropy decreased very slowly and became not significant (Figure 1A). C and G are two exceptions. For C (Figure 2A), the highest relative entropies appeared at the third flanking sites of both N- and C-termini. Without these sites, relative entropies were relatively low. For G (Figure 3A), the relative entropies of N- and C-terminal flanking sites showed an evident periodic change, that is, relative entropies were remarkably high in all of the 3n (n = ±1, ±2, ±3…) flanking sites; other sites showed low values. The peaks at the 3n flanking sites decreased gradually when the distance to the 0 site increased. To determine the specific amino acids responsible for the high relative entropy at one flanking site, we further investigated the 20 relative entropies calculated using at each flanking site of the 20 amino acids (Figure 1B, Figure 2B, and Figure 3B). We found that for more than half of the amino acids (A, L, V, P, G, S, T, Q, C, H, K, R, D, and E), the corresponding residues tended to show high propensity at the neighboring sites (e.g., in Figure 1B, amino acid A was a outlier which was above the upper whisker of the boxplot in each flanking site, which demonstrated that amino acid A was a type of preferred amino acid in the neighboring sites of amino acid A).

Bottom Line: Our results showed that nearly half of 380 substitution types were evidently context dependent, and the context-dependent patterns relied on protein secondary structures.Among 20 amino acids, P elicited the greatest effect on amino acid substitutions.The underlying mechanisms of context-dependent effects of amino acid substitutions were possibly mutation bias at a DNA level and natural selection.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences and State Key Laboratory of Crop Stress Biology in Arid Areas, Northwest A&F University, Yangling 712100, China. fmcsky@nwsuaf.edu.cn.

ABSTRACT
Amino acids show apparent propensities toward their neighbors. In addition to preferences of amino acids for their neighborhood context, amino acid substitutions are also considered to be context-dependent. However, context-dependence patterns of amino acid substitutions still remain poorly understood. Using relative entropy, we investigated the neighbor preferences of 20 amino acids and the context-dependent effects of amino acid substitutions with protein sequences in human, mouse, and dog. For 20 amino acids, the highest relative entropy was mostly observed at the nearest adjacent site of either N- or C-terminus except C and G. C showed the highest relative entropy at the third flanking site and periodic pattern was detected at G flanking sites. Furthermore, neighbor preference patterns of amino acids varied greatly in different secondary structures. We then comprehensively investigated the context-dependent effects of amino acid substitutions. Our results showed that nearly half of 380 substitution types were evidently context dependent, and the context-dependent patterns relied on protein secondary structures. Among 20 amino acids, P elicited the greatest effect on amino acid substitutions. The underlying mechanisms of context-dependent effects of amino acid substitutions were possibly mutation bias at a DNA level and natural selection. Our findings may improve secondary structure prediction algorithms and protein design; moreover, this study provided useful information to develop empirical models of protein evolution that consider dependence between residues.

Show MeSH
Related in: MedlinePlus