Yeast metabolic innovations emerged via expanded metabolic network and gene positive selection

Hongzhong Lu; Feiran Li; Le Yuan; Iván Domenzain Del Castillo Cerecer; Rosemary Brown; Hao Wang; Gang Li; Yu Chen; Boyang Ji; Eduard Kerkhoven; Jens B Nielsen

doi:10.15252/msb.202110427

Yeast metabolic innovations emerged via expanded metabolic network and gene positive selection
Journal article, 2021

Yeasts are known to have versatile metabolic traits, while how these metabolic traits have evolved has not been elucidated systematically. We performed integrative evolution analysis to investigate how genomic evolution determines trait generation by reconstructing genome-scale metabolic models (GEMs) for 332 yeasts. These GEMs could comprehensively characterize trait diversity and predict enzyme functionality, thereby signifying that sequence-level evolution has shaped reaction networks towards new metabolic functions. Strikingly, using GEMs, we can mechanistically map different evolutionary events, e.g. horizontal gene transfer and gene duplication, onto relevant subpathways to explain metabolic plasticity. This demonstrates that gene family expansion and enzyme promiscuity are prominent mechanisms for metabolic trait gains, while GEM simulations reveal that additional factors, such as gene loss from distant pathways, contribute to trait losses. Furthermore, our analysis could pinpoint to specific genes and pathways that have been under positive selection and relevant for the formulation of complex metabolic traits, i.e. thermotolerance and the Crabtree effect. Our findings illustrate how multidimensional evolution in both metabolic network structure and individual enzymes drives phenotypic variations.

genome analysis

metabolic innovation

systems biology

genome-scale metabolic models