Substitutional Analysis of Orthologous Protein Families Using BLOCKS

Abstract

Orthologous proteins, form due to divergence of parental sequence, perform similar function under different environmental and biological conditions. Amino acid changes at locus specific positions form hetero-pairs whose role in BLOCK evolution is yet to be understood. We involve eight protein BLOCKs of known divergence rate to gain insight into the role of hetero-pairs in evolution. Our procedure APBEST uses BLOCK-FASTA file to extract BLOCK specific evolutionary parameters such as dominantly used hetero-pair (D), usage of hetero-pairs (E), non-conservative to conservative substitution ratio (R), maximally-diverse residue (MDR), residue (RD) and class (CD) specific diversity. All these parameters show BLOCK specific variation. Conservative nature of D points towards restoration of function of BLOCK. While E sets the upper-limit of usage of hereto-pairs, strong correlation of R with divergence-rate indicates that the later is directly dependent on non-conservative substitutions. The observation that MDR, measure of positional diversity, occupy very limited positions in BLOCK indicates accommodation of diversity is positionally restricted. Overall, the study extract observed hetero-pair related quantitative and multi-parametric details of BLOCK, which finds application in evolutionary biology.

Keywords: conservative; divergence rate; evolution; hetero-pairs; non-conservative; substitution.

Figure 1

Flowchart describing methodology and operation of APBEST for extraction of analytical parameters from orthologous protein family.

Figure 2

APBEST implemented equations and their clarity.

Figure 3

190 SHP types (upper-half of diagonal) and observed frequencies (lower-half of diagonal) are shown. Substitution-homo-pair frequencies (i.e. 20) are at the diagonal position. Both these types and their frequencies divided into three categories: a] HB-HB category: total 36 (upper dark shade), b] HL-HL category: total 55 (lower white shade) and HB-HL category: 99 in number (middle gray shade region). Residue Q is shown by gray-strip for explanation of the calculation of diversity of a given hetero-pair.

Figure 4

Plot of derived ratios (R and E) vs. divergence rate and observed hetero-pair frequency vs. probability range. Two typical frequency distributions are shown (Graph A1 and Graph A2) where the observed-data are fitted with Weibull distribution function. Used (E) fraction of hetero-pair is plotted against divergence rate (Graph B). Graph C, shows the correlation between R with divergence rate [6,7].