The evolution of metabolic enzymes in Plasmodium and trypanosomatids as compared to Saccharomyces and Schizosaccharomyces

Understanding how the biological connectivity of genes and gene products affects evolution is an important aspect of understanding evolution. Genes encoding enzymes are frequently used to carry out such analyses. Interestingly, studies have shown that connectivity in the metabolic networks in parasitic protists, including Plasmodium falciparum and Trypanosoma brucei, have been substantially altered as compared to free living eukaryotes, such as Saccharomyces cerevisiae. Herein, we have determined Ka values, which are a measure of the non-synonymous substitution rate, and used them to examine the differences between the evolution of genes in T. brucei, P. falciparum, S. cerevisiae, and Schizosaccharomyces pombe. All four organisms share similar traits with respect to the evolution of genes encoding metabolic enzymes. First, genes encoding metabolic enzymes have lower Ka values than genes encoding non-metabolic proteins. In addition, perturbations of the metabolic network appear to have limited affects on the genes encoding enzymes near the perturbation. In most cases, there is a negative relationship between connectivity in the metabolic network of the gene product and the Ka value for the gene, i.e. examining how much constraint there is on gene evolution when it is connected to many other genes. In addition, we find that the Ka values of orthologs encoding for metabolic enzymes in each organism are significantly correlated, indicating similar patterns of non-synonymous substitutions. In total, our results indicate that the evolution of genes encoding metabolic enzymes do not tend to be greatly affected by changes in the metabolic network.

Ka was calculated by comparing T. brucei genes to the corresponding orthologs in the given organisms. The mean Ka and the standard error are displayed.Figure optionsDownload high-quality image (140 K)Download as PowerPoint slideHighlights
► Genes encoding enzymes evolve differently than genes encoding non-metabolic proteins.
► In a significant number of cases tested, there is a link between connectivity and evolution.
► Genes encoding enzymes in the organism analyzed have evolved similarly.