Signatures of optimal codon usage in metabolic genes inform budding yeast ecology.

Dana A. Opulente,Antonis Rokas,Chris Todd Hittinger,Abigail Leavitt LaBella,Jacob L. Steenwyk

doi:10.1371/journal.pbio.3001185

Abstract

Reverse ecology is the inference of ecological information from patterns of genomic variation. One rich, heretofore underutilized, source of ecologically relevant genomic information is codon optimality or adaptation. Bias toward codons that match the tRNA pool is robustly associated with high gene expression in diverse organisms, suggesting that codon optimization could be used in a reverse ecology framework to identify highly expressed, ecologically relevant genes. To test this hypothesis, we examined the relationship between optimal codon usage in the classic galactose metabolism (GAL) pathway and known ecological niches for 329 species of budding yeasts, a diverse subphylum of fungi. We find that optimal codon usage in the GAL pathway is positively correlated with quantitative growth on galactose, suggesting that GAL codon optimization reflects increased capacity to grow on galactose. Optimal codon usage in the GAL pathway is also positively correlated with human-associated ecological niches in yeasts of the CUG-Ser1 clade and with dairy-associated ecological niches in the family Saccharomycetaceae. For example, optimal codon usage of GAL genes is greater than 85% of all genes in the genome of the major human pathogen Candida albicans (CUG-Ser1 clade) and greater than 75% of genes in the genome of the dairy yeast Kluyveromyces lactis (family Saccharomycetaceae). We further find a correlation between optimization in the GALactose pathway genes and several genes associated with nutrient sensing and metabolism. This work suggests that codon optimization harbors information about the metabolic ecology of microbial eukaryotes. This information may be particularly useful for studying fungal dark matter-species that have yet to be cultured in the lab or have only been identified by genomic material.

Highlights

The immense diversity of life is due, in part, to adaptation to the wide variety of environmental niches available
To examine if our analysis enables the prediction of growth rate on galactose-containing media, we analyzed the codon optimization of the galactose metabolism (GAL) pathway in 2 species not included in the original dataset—K. wickerhamii (Saccharomycetaceae) and W. occidentalis (Dipodascaceae/Trichomonascaceae clade)
The conceptual evolutionary model for this association (Fig 5) is that selection for increased rates of galactose metabolism in galactose-rich environments will result in selection for optimization of codon usage in the GAL genes

Summary

Introduction

The immense diversity of life is due, in part, to adaptation to the wide variety of environmental niches available. Elucidating the precise relationship between genotype, phenotype, and environment, is often challenging. Genomic sequencing has accelerated the rate at which the underlying genomic mechanisms of well-established ecologically adapted phenotypes are elucidated [7,8]. While powerful, this type of ecological genomics requires extensive knowledge of the ecological niche in which species live. One potentially powerful way to address this gap in knowledge is to use the extensive genomic resources available in microbes to conduct reverse ecology—directly predicting ecology from genotype [10,11]

Methods

Results

Conclusion