Insights on the Evolution of Metabolic Networks of Unicellular Translationally Biased Organisms from Transcriptomic Data and Sequence Analysis

Abstract

Abstract. Codon bias is related to metabolic functions in translationally biased organisms, and two facts are argued about. First, genes with high codon bias describe in meaningful ways the metabolic characteristics of the organism; important metabolic pathways corresponding to crucial characteristics of the lifestyle of an organism, such as photosynthesis, nitrification, anaerobic versus aerobic respiration, sulfate reduction, methanogenesis, and others, happen to involve especially biased genes. Second, gene transcriptional levels of sets of experiments representing a significant variation of biological conditions strikingly confirm, in the case of Saccharomyces cerevisiae, that metabolic preferences are detectable by purely statistical analysis: the high metabolic activity of yeast during fermentation is encoded in the high bias of enzymes involved in the associated pathways, suggesting that this genome was affected by a strong evolutionary pressure that favored a predominantly fermentative metabolism of yeast in the wild. The ensemble of metabolic pathways involving enzymes with high codon bias is rather well defined and remains consistent across many species, even those that have not been considered as translationally biased, such as Helicobacter pylori, for instance, reveal some weak form of translational bias for this genome. We provide numerical evidence, supported by experimental data, of these facts and conclude that the metabolic networks of translationally biased genomes, observable today as projections of eons of evolutionary pressure, can be analyzed numerically and predictions of the role of specific pathways during evolution can be derived. The new concepts of Comparative Pathway Index, used to compare organisms with respect to their metabolic networks, and Evolutionary Pathway Index, used to detect evolutionarily meaningful bias in the genetic code from transcriptional data, are introduced.

Translational Selection Is Ubiquitous in Prokaryotes

“…The most prominent trend in our results is consistent with previous research [28], [33], with translational selection readily acting on genes involved in protein production and in energy metabolism. Genes that are rarely OCU are involved in regulation, DNA replication and repair, sensing of stimuli, and most kinds of transport, except the electron transport chain and ATP synthesis-coupled H + transport.…”

“…If organisms defined by a specific lifestyle show a tendency contrary to the general trend, and this tendency is constrained to a gene functional category, this correlation could be biologically meaningful. An example illustrative of this principle was previously brought forward in work by Karlin [40] and Carbone [28], where the glycolysis genes were claimed to be more frequently codon-optimized in anaerobic bacteria. Indeed, we detected this association (GO∶6096, enrichment = 2.1x, p  = 10 −33 ) alongside with a – not unexpected – increase in OCU frequency of carbohydrate transporters (GO∶8643, enrichment = 1.8x, p  = 10 −14 ).…”

“…Interestingly, several authors that relied on a codon distance measure have found that gene functions close in codon usage to RP genes in E. coli also have RP-like codon usage in some of the organisms which are supposed to lack translational selection, see e.g. the glycolysis genes in H. pylori [28] or respiration and ATP synthase genes in B. floridanus [29].…”

Chromosomal periodicity and positional networks of genes in Escherichia coli

“…They organize in two different positional networks, which occupy distinguished chromosomal ‘facets' over the same period (Figure 5A; Supplementary Figure 8). It might appear striking that the set of genes involved in E. coli K12 metabolism is periodically organized in the same way as the set of core genes (compare violet and red curves in Figure 5A), but in fact, core genes have been used already in Carbone and Madden (2005) to identify key metabolic networks for a number of bacteria, including E. coli K12 , and to highlight that genes involved in metabolism are subject to a strong evolutionary pressure on their codon bias. Our current finding adds a new insight on our understanding of the evolutionary pressure undergoing metabolic pathways, reporting that these genes need also to preserve a regular positional distribution along the chromosome.…”

The Impact of Selection at the Amino Acid Level on the Usage of Synonymous Codons

“…However, the analysis of many genomes has revealed that there is a fraction of genes that show no evidence for translational selection linked to codon usage (Carbone and Madden 2005; dos Reis et al 2004; Sharp et al 2005). This observation is not supported by recent, multi-genome, studies indicating that the translational selection for codon usage seems universal, at least in prokaryotes (Hershberg and Petrov 2008; Supek et al 2010) and plastids (Suzuki and Morton 2016).…”