{"doi":"10.1371/journal.pcbi.1008596","title":"Bacterial fitness landscapes stratify based on proteome allocation associated with discrete aero-types","abstract":"The fitness landscape is a concept commonly used to describe evolution towards optimal phenotypes. It can be reduced to mechanistic detail using genome-scale models (GEMs) from systems biology. We use recently developed GEMs of Metabolism and protein Expression (ME-models) to study the distribution of Escherichia coli phenotypes on the rate-yield plane. We found that the measured phenotypes distribute non-uniformly to form a highly stratified fitness landscape. Systems analysis of the ME-model simulations suggest that this stratification results from discrete ATP generation strategies. Accordingly, we define \"aero-types\", a phenotypic trait that characterizes how a balanced proteome can achieve a given growth rate by modulating 1) the relative utilization of oxidative phosphorylation, glycolysis, and fermentation pathways; and 2) the differential employment of electron-transport-chain enzymes. This global, quantitative, and mechanistic systems biology interpretation of fitness landscape formed upon proteome allocation offers a fundamental understanding of bacterial physiology and evolution dynamics.","journal":"PLoS Computational Biology","year":2021,"id":178112,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314815,"name":"Amitesh Anand","orcid":"0000-0002-3720-4301","position":1,"is_corresponding":false},{"id":559196,"name":"Connor A. Olson","orcid":"0000-0003-3681-0446","position":2,"is_corresponding":false},{"id":468012,"name":"Troy E. Sandberg","orcid":"0000-0003-3240-3659","position":3,"is_corresponding":false},{"id":560338,"name":"Ye Gao","orcid":"0000-0001-8519-1392","position":4,"is_corresponding":false},{"id":5431,"name":"Nathan Mih","orcid":"0000-0002-4302-9052","position":5,"is_corresponding":false},{"id":5441,"name":"Bernhard Ø. Palsson","orcid":"0000-0003-2357-6785","position":6,"is_corresponding":false},{"id":723238,"name":"Ke Chen","orcid":"0000-0003-2089-1288","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-18T23:47:36.112170Z","pmid":"33465077","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}