{"doi":"10.1101/gr.1589103","title":"Gene Loss, Protein Sequence Divergence, Gene Dispensability, Expression Level, and Interactivity Are Correlated in Eukaryotic Evolution","abstract":"<jats:p>Lineage-specific gene loss, to a large extent, accounts for the differences in gene repertoires between genomes, particularly among eukaryotes. We derived a parsimonious scenario ofgene losses for eukaryotic orthologous groups (KOGs) from seven complete eukaryotic genomes. The scenario involves substantial gene loss in fungi, nematodes, and insects. Based on this evolutionary scenario and estimates of the divergence times between major eukaryotic phyla, we introduce a numerical measure, the propensity for gene loss (PGL). We explore the connection among the propensity of a gene to be lost in evolution (PGL value), protein sequence divergence, the effect of gene knockout on fitness, the number of protein-protein interactions, and expression level for the genes in KOGs. Significant correlations between PGL and each of these variables were detected. Genes that have a lower propensity to be lost in eukaryotic evolution accumulate fewer substitutions in their protein sequences and tend to be essential for the organism viability, tend to be highly expressed, and have many interaction partners. The dependence between PGL and gene dispensability and interactivity is much stronger than that for sequence evolution rate. Thus, propensity of a gene to be lost during evolution seems to be a direct reflection of its biological importance.</jats:p>","journal":"Genome Research","year":2003,"id":588860,"datarank":14.068362316241869,"base_score":6.023447592961033,"endowment":6.023447592961033,"self_citation_contribution":0.9035171389441551,"citation_network_contribution":13.164845177297714,"self_endowment_contribution":0.9035171389441551,"citer_contribution":13.164845177297714,"corpus_percentile":null,"corpus_rank":null,"citation_count":412,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":107326,"name":"Yuri I. Wolf","orcid":"0000-0002-0247-8708","position":1,"is_corresponding":false},{"id":181046,"name":"Igor B. Rogozin","orcid":null,"position":2,"is_corresponding":false},{"id":17837,"name":"Eugene V. Koonin","orcid":"0000-0003-3943-8299","position":3,"is_corresponding":false},{"id":1506623,"name":"Dmitri M. Krylov","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Gene Loss, Protein Sequence Divergence, Gene Dispensability, Expression Level, and Interactivity Are Correlated in Eukaryotic Evolution","abstract":"<jats:p>Lineage-specific gene loss, to a large extent, accounts for the differences in gene repertoires between genomes, particularly among eukaryotes. We derived a parsimonious scenario ofgene losses for eukaryotic orthologous groups (KOGs) from seven complete eukaryotic genomes. The scenario involves substantial gene loss in fungi, nematodes, and insects. Based on this evolutionary scenario and estimates of the divergence times between major eukaryotic phyla, we introduce a numerical measure, the propensity for gene loss (PGL). We explore the connection among the propensity of a gene to be lost in evolution (PGL value), protein sequence divergence, the effect of gene knockout on fitness, the number of protein-protein interactions, and expression level for the genes in KOGs. Significant correlations between PGL and each of these variables were detected. Genes that have a lower propensity to be lost in eukaryotic evolution accumulate fewer substitutions in their protein sequences and tend to be essential for the organism viability, tend to be highly expressed, and have many interaction partners. The dependence between PGL and gene dispensability and interactivity is much stronger than that for sequence evolution rate. Thus, propensity of a gene to be lost during evolution seems to be a direct reflection of its biological importance.</jats:p>","is_dataset_classified":null,"base_score":6.023447592961033,"endowment":6.023447592961033,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"14525925","pmcid":"PMC403683","openalex_id":"https://openalex.org/W2102225814","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2012,"count":17},{"year":2013,"count":21},{"year":2014,"count":25},{"year":2015,"count":22},{"year":2016,"count":23},{"year":2017,"count":15},{"year":2018,"count":17},{"year":2019,"count":14},{"year":2020,"count":20},{"year":2021,"count":16},{"year":2022,"count":8},{"year":2023,"count":9},{"year":2024,"count":12},{"year":2025,"count":6},{"year":2026,"count":3}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://genome.cshlp.org/content/13/10/2229.full.pdf","host_type":"journal"},{"url":"https://genome.cshlp.org/content/13/10/2229.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1101/gr.1589103","host_type":"publisher"},{"url":"https://doi.org/10.1101/gr.1589103","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/14525925","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/403683","host_type":"repository"}],"fields_of_study":["Fungal and yeast genetics research","Genomics and Phylogenetic Studies","Evolution and Genetic Dynamics","Amino Acid Substitution","Animals","Conserved Sequence","Encephalitozoon cuniculi","Eukaryotic Cells","Evolution, Molecular","Fungal Proteins","Gene Deletion","Gene Expression Regulation","Gene Expression Regulation, Fungal","Genes, Essential","Genes, Fungal","Genes, Protozoan","Genetic Variation","Humans","Phylogeny","Protein Interaction Mapping","Protein Structure, Secondary","Proteins","Protozoan Proteins","Reference Values","Saccharomyces cerevisiae","Saccharomyces cerevisiae Proteins","Schizosaccharomyces","Sequence Homology, Nucleic Acid"],"mesh_terms":["Animals","Eukaryotic Cells","Fungal Proteins","Gene Expression Regulation","Genes, Fungal","Humans","Encephalitozoon cuniculi","Phylogeny","Proteins","Reference Values","Saccharomyces cerevisiae","Schizosaccharomyces","Sequence Homology, Nucleic Acid","Genetic Variation","Protozoan Proteins","Gene Expression Regulation, Fungal","Conserved Sequence","Genes, Protozoan","Gene Deletion","Protein Structure, Secondary","Evolution, Molecular","Amino Acid Substitution","Genes, Essential","Protein Interaction Mapping","Saccharomyces cerevisiae Proteins"],"keywords":["Biology","Gene","Genetics","Genome","Evolutionary biology","Rate of evolution","Genome evolution","Lineage (genetic)","Gene expression","Regulation of gene expression","Phylogenetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-22T23:16:00.384963Z","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":[]}