Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins - PubMed (original) (raw)

Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins

I K Jordan et al. Genome Biol. 2001.

Abstract

Background: Detection of changes in a protein's evolutionary rate may reveal cases of change in that protein's function. We developed and implemented a simple relative rates test in an attempt to assess the rate constancy of protein evolution and to detect cases of functional diversification between orthologous proteins. The test was performed on clusters of orthologous protein sequences from complete bacterial genomes (Chlamydia trachomatis, C. muridarum and Chlamydophila pneumoniae), complete archaeal genomes (Pyrococcus horikoshii, P. abyssi and P. furiosus) and partially sequenced mammalian genomes (human, mouse and rat).

Results: Amino-acid sequence evolution rates are significantly correlated on different branches of phylogenetic trees representing the great majority of analyzed orthologous protein sets from all three domains of life. However, approximately 1% of the proteins from each group of species deviates from this pattern and instead shows variation that is consistent with an acceleration of the rate of amino-acid substitution, which may be due to functional diversification. Most of the putative functionally diversified proteins from all three species groups are predicted to function at the periphery of the cells and mediate their interaction with the environment.

Conclusions: Relative rates of protein evolution are remarkably constant for the three species groups analyzed here. Deviations from this rate constancy are probably due to changes in selective constraints associated with diversification between orthologs. Functional diversification between orthologs is thought to be a relatively rare event. However, the resolution afforded by the test designed specifically for genomic-scale datasets allowed us to identify numerous cases of possible functional diversification between orthologous proteins.

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Figures

Figure 1

Figure 1

Schematic of an orthologous protein phylogeny and the null hypothesis (Ho) of a constant relative rate of protein evolution. Comparison of multiple orthologous proteins is predicted to reveal a constant relative rate of evolution. This should be manifest as an approximately constant ratio of phylogenetic branch lengths (bold lines) bA/(bB + bC). The branch lengths were calculated using the evolutionary distances (dashed lines) between the proteins from three species (dAB, dAC, dBC) as described in Materials and methods.

Figure 2

Figure 2

Phylogenies of the three analyzed species groups. Branch lengths are the average of all branch lengths for a given species group. The different branches bA, bB and bC are indicated.

Figure 3

Figure 3

Correlation between the branch lengths in different phylogenetic partitions. Linear regression where the bA branch length (_y_-axis) is plotted against the sum of bB + bC branch lengths (_x_-axis) for all orthologous protein sets of each species group. (a) Chlamydiaceae species group including C. pneumoniae, C. muridarum and C. trachomatis. (b)Pyrococcus species group including P. furiosus, P. abyssi and P. horikoshii. (c) Human-mouse-rat species group including H. sapiens, M. musculus and R. norvegicus. The equation for the linear regression trend line (y = mx + b), the correlation coefficient (r) and the level of significance for the correlation (P) are shown on each plot. The linear regression trend line is shown in bold black and the upper and lower limits, corresponding to an expectation value of 0.05, are shown in light gray. For each plot, only 0.05 points are expected to fall outside of these limits by chance. All values are shown as diamonds and the values outside the upper and lower limits that represent functionally diversified orthologous protein sets are indicated by larger squares.

Figure 4

Figure 4

Non-synonymous (Ka) versus synonymous (Ks) substitution rates for the human-mouse-rat orthologous protein sets. (a) Average Ks and Ka for the human-mouse and human-rat pairwise comparisons. (b) Ks and Ka for the mouse-rat pairwise comparisons. Thick diagonal line, Ks = Ka; thin horizontal line, average Ka. All values are shown with circles and the values corresponding to the functionally diversified proteins are indicated by larger squares.

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