Data integration uncovers the metabolic bases of phenotypic variation in yeast

PLoS Comput Biol. 2021 Jul 15;17(7):e1009157. doi: 10.1371/journal.pcbi.1009157. eCollection 2021 Jul.

Abstract

The relationship between different levels of integration is a key feature for understanding the genotype-phenotype map. Here, we describe a novel method of integrated data analysis that incorporates protein abundance data into constraint-based modeling to elucidate the biological mechanisms underlying phenotypic variation. Specifically, we studied yeast genetic diversity at three levels of phenotypic complexity in a population of yeast obtained by pairwise crosses of eleven strains belonging to two species, Saccharomyces cerevisiae and S. uvarum. The data included protein abundances, integrated traits (life-history/fermentation) and computational estimates of metabolic fluxes. Results highlighted that the negative correlation between production traits such as population carrying capacity (K) and traits associated with growth and fermentation rates (Jmax) is explained by a differential usage of energy production pathways: a high K was associated with high TCA fluxes, while a high Jmax was associated with high glycolytic fluxes. Enrichment analysis of protein sets confirmed our results. This powerful approach allowed us to identify the molecular and metabolic bases of integrated trait variation, and therefore has a broad applicability domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Variation, Population / genetics
  • Biological Variation, Population / physiology
  • Computational Biology / methods*
  • Databases, Genetic
  • Fermentation / genetics
  • Glycolysis / genetics
  • Phenotype
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism

Associated data

  • figshare/10.6084/m9.figshare.10266332

Grants and funding

MSP was funded with a public Ph.D. grant from the French National Research Agency (ANR) as part of the Investissement d’Avenir program, through the Initiative Doctorale Interdisciplinaire (IDI) 2015 project funded by the Initiative d’Excellence (IDEX) Paris-Saclay, ANR-11-IDEX-0003-02. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.