{"doi":"10.1101/2022.02.08.479609","title":"A bacterial pan-genome makes gene essentiality strain-dependent and evolvable","abstract":"Abstract Many bacterial species are represented by a pan-genome, whose genetic repertoire far outstrips that of any single bacterial genome. Here we investigate how a bacterial pan-genome might influence gene essentiality, and whether essential genes that are initially critical for the survival of an organism can evolve to become non-essential. By using Tn-Seq, whole-genome sequencing, and RNA-Seq on a set of 36 clinical Streptococcus pneumoniae strains representative of >68% of the species’ pan-genome, we identify a species-wide ‘essentialome’ that can be subdivided into universal, strain-specific and accessory essential genes. By employing ‘forced-evolution experiments’ we show that specific genetic changes allow bacteria to bypass essentiality. Moreover, by untangling several genetic mechanisms we show that gene-essentiality can be highly influenced and/or dependent on: 1) the composition of the accessory genome; 2) the accumulation of toxic intermediates; 3) functional redundancy; 4) efficient recycling of critical metabolites; and 5) pathway rewiring. While this functional characterization underscores the evolvability-potential of many essential genes, we also show that genes with differential essentiality remain important antimicrobial drug target candidates, as their inactivation almost always has a severe fitness cost in vivo .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298154,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9212,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":847040,"name":"Emily Rudmann","orcid":null,"position":1,"is_corresponding":false},{"id":806987,"name":"Jien Li","orcid":"0000-0003-1200-9611","position":2,"is_corresponding":false},{"id":331273,"name":"Defne Surujon","orcid":"0000-0001-7964-3057","position":3,"is_corresponding":false},{"id":847041,"name":"Jon Anthony","orcid":null,"position":4,"is_corresponding":false},{"id":598820,"name":"Matthew W. Frank","orcid":"0000-0002-4914-1440","position":5,"is_corresponding":false},{"id":693521,"name":"Dakota S. Jones","orcid":"0000-0002-8423-6840","position":6,"is_corresponding":false},{"id":469113,"name":"Charles O. Rock","orcid":"0000-0001-8648-4189","position":7,"is_corresponding":false},{"id":275853,"name":"Jason W. Rosch","orcid":"0000-0002-1798-1760","position":8,"is_corresponding":false},{"id":658716,"name":"Christopher D. Johnston","orcid":"0000-0002-6765-2383","position":9,"is_corresponding":false},{"id":228745,"name":"Tim van Opijnen","orcid":"0000-0001-6895-6795","position":10,"is_corresponding":false},{"id":845956,"name":"Federico Rosconi","orcid":"0000-0001-6760-9003","position":0,"is_corresponding":true}],"reference_count":103,"raw_metadata":null,"created_at":"2026-07-19T00:31:31.270564Z","pmid":null,"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":[]}