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Author: Jordan, I. King × Author: Koonin, Eugene V. × Author: Rogozin, Igor B. × End date: 2010 × Start date: 2001 × Has files: Yes × search.filters.applied.f.isOrgUnitOfPublicationTitle: School of Biological Sciences ×

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    Essential genes are more evolutionarily conserved than non-essential genes in bacteria
    (Georgia Institute of Technology, 2002-06) Jordan, I. King ; Rogozin, Igor B. ; Wolf, Yuri I. ; Koonin, Eugene V.
    The “knockout-rate” prediction holds that essential genes should be more evolutionarily conserved than are nonessential genes. This is because negative (purifying) selection acting on essential genes is expected to be more stringent than that for nonessential genes, which are more functionally dispensable and/or redundant. However, a recent survey of evolutionary distances between Saccharomyces cerevisiae and Caenorhabditis elegans proteins did not reveal any difference between the rates of evolution for essential and nonessential genes. An analysis of mouse and rat orthologous genes also found that essential and nonessential genes evolved at similar rates when genes thought to evolve under directional selection were excluded from the analysis. In the present study, we combine genomic sequence data with experimental knockout data to compare the rates of evolution and the levels of selection for essential versus nonessential bacterial genes. In contrast to the results obtained for eukaryotic genes, essential bacterial genes appear to be more conserved than are nonessential genes over both relatively short (microevolutionary) and longer (macroevolutionary) time scales. Rates of evolution vary tremendously among protein-coding genes. Molecular evolutionary studies have revealed an ∼1000-fold range of nonsynonymous substitution rates (Li and Graur 1991). The strength of negative (purifying) selection is thought to be the most important factor in determining the rate of evolution for the protein-coding regions of a gene (Kimura 1983; Ohta 1992; Li 1997). Consistent with this idea, Alan Wilson and colleagues (1997) proposed that essential genes should evolve more slowly than nonessential genes. This is the so-called “knockout-rate” prediction (Hurst and Smith 1999). “Essential” and “nonessential” are classic molecular genetic designations that relate to the functional significance of a gene with respect to its effect on organismic fitness. A gene is considered to be essential if a knock-out results in (conditional) lethality or infertility. On the other hand, nonessential genes are those for which knock-outs yield viable and fertile individuals. It was reasoned that purifying selection should be more intense for essential genes because they are, by definition, less functionally dispensable and/or redundant than are nonessential genes. Given the role of purifying selection in determining evolutionary rates, the greater levels of purifying selection on essential genes should be manifest as a lower rate of evolution relative to that of nonessential genes. To systematically evaluate the relationship between the fitness effects of genes and their rates of evolution, a combination of a substantial amount of experimental knock-out data and sequence data from numerous genes is required. Only recently has enough data accumulated to allow for tests of the straightforward and seemingly intuitive knock-out rate prediction. However, examinations of sequence data with respect to this prediction have yielded equivocal results. For example, a survey of substitution rates for mouse and rat orthologous genes appeared to indicate a slower rate of evolution for essential genes. But when genes thought to evolve under directional selection were excluded from the analysis, essential and nonessential genes were found to evolve at similar rates (Hurst and Smith 1999). A more recent analysis of the evolutionary distances between Saccharomyces cerevisiae and Caenorhabditis elegans proteins did indicate that the fitness effect of a protein influences its rate of evolution (Hirsh and Fraser 2001). Nevertheless, this study (Hirsh and Fraser 2001) was also unable to reveal any difference between the rates of evolution for essential and nonessential genes. The results from both of these studies were taken to indicate that the fitness differences between essential and nonessential genes do not influence evolutionary rates to the extent that was expected. However, the studies relied on the analyses of relatively few genes (n = 175 and n = 287, respectively) and comparisons between species that diverged at least tens of millions of years ago. It might be the case that these results reflect a lack of power and sensitivity of the approaches that were used. The recent availability of complete genome sequences from different strains of the same bacterial species provides an opportunity to address the issue with an unprecedented level of resolution. In the present study, to test the knockout-rate prediction, the relationship between the fitness class of genes (essential versus nonessential) and their rate of evolution was assessed for three bacterial species: Escherichia coli, Helicobacter pylori, and Neisseria meningitidis, for each of which at least two complete genome sequences are available.
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    Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins
    (Georgia Institute of Technology, 2001-11-20) Jordan, I. King ; Kondrashov, Fyodor A. ; Rogozin, Igor B. ; Tatusov, Roman L. ; Wolf, Yuri I. ; Koonin, Eugene V.
    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.