{"doi":"10.1073/pnas.97.2.704","title":"Functional evolution of the Ultrabithorax protein","abstract":"<jats:p>The Hox genes have been implicated as central to the evolution of animal body plan diversity. Regulatory changes both in Hox expression domains and in Hox-regulated gene networks have arisen during the evolution of related taxa, but there is little knowledge of whether functional changes in Hox proteins have also contributed to morphological evolution. For example, the evolution of greater numbers of differentiated segments and body parts in insects, compared with the simpler body plans of arthropod ancestors, may have involved an increase in the spectrum of biochemical interactions of individual Hox proteins. Here, we compare the<jats:italic>in vivo</jats:italic>functions of orthologous Ultrabithorax (Ubx) proteins from the insect<jats:italic>Drosophila melanogaster</jats:italic>and from an onychophoran, a member of a sister phylum with a more primitive and homonomous body plan. These Ubx proteins, which have been diverging in sequence for over 540 million years, can generate many of the same gain-of-function tissue transformations and can activate and repress many of the same target genes when expressed during<jats:italic>Drosophila</jats:italic>development. However, the onychophora Ubx (OUbx) protein does not transform the segmental identity of the embryonic ectoderm or repress the<jats:italic>Distal-less</jats:italic>target gene. This functional divergence is due to sequence changes outside the conserved homeodomain region. The inability of OUbx to function like<jats:italic>Drosophila</jats:italic>Ubx (DUbx) in the embryonic ectoderm indicates that the Ubx protein may have acquired new cofactors or activity modifiers since the divergence of the onychophoran and insect lineages.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2000,"id":25319,"datarank":4.785006838228647,"base_score":4.465908118654584,"endowment":4.465908118654584,"self_citation_contribution":0.6698862177981877,"citation_network_contribution":4.115120620430459,"self_endowment_contribution":0.6698862177981877,"citer_contribution":4.115120620430459,"corpus_percentile":null,"corpus_rank":null,"citation_count":86,"citer_count":82,"citers_with_citation_signal":72,"citers_with_endowment":72,"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":115374,"name":"Sean B. Carroll","orcid":null,"position":1,"is_corresponding":false},{"id":54719,"name":"Jennifer K. Grenier","orcid":"0000-0002-0928-7971","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.465908118654584,"endowment":4.465908118654584,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10639143","pmcid":"PMC15394","openalex_id":"https://openalex.org/W2049717930","authors":[],"funders":[],"total_grants":0,"fwci":20.0269,"citation_percentile":0.99416661,"influential_citations":11,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":1},{"year":2014,"count":2},{"year":2015,"count":3},{"year":2016,"count":3},{"year":2017,"count":2},{"year":2018,"count":2},{"year":2020,"count":2},{"year":2022,"count":1},{"year":2023,"count":2},{"year":2024,"count":3}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://doi.org/10.1073/pnas.97.2.704","host_type":"GREEN"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.97.2.704","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10639143","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/15394","host_type":"repository"}],"fields_of_study":["Tardigrade Biology and Ecology","Developmental Biology and Gene Regulation","Protist diversity and phylogeny","Biology","Medicine","Amino Acid Sequence","Animals","Arthropods","Body Patterning","DNA-Binding Proteins","Drosophila Proteins","Drosophila melanogaster","Embryo, Nonmammalian","Evolution, Molecular","Extremities","Female","Gene Expression Regulation","Genetic Variation","Homeodomain Proteins","Insect Proteins","Male","Molecular Sequence Data","Phenotype","Sequence Homology, Amino Acid","Transcription Factors","Transformation, Genetic"],"mesh_terms":["Amino Acid Sequence","Animals","Arthropods","DNA-Binding Proteins","Drosophila melanogaster","Embryo, Nonmammalian","Extremities","Female","Gene Expression Regulation","Male","Molecular Sequence Data","Phenotype","Transcription Factors","Transformation, Genetic","Genetic Variation","Sequence Homology, Amino Acid","Homeodomain Proteins","Evolution, Molecular","Insect Proteins","Body Patterning","Drosophila Proteins"],"keywords":["Ultrabithorax","Hox gene","Biology","Homeotic gene","Homeobox","Body plan","Ectoderm","Genetics","Evolutionary biology","Functional divergence","Drosophila melanogaster","engrailed","Decapentaplegic","Gene","Most recent common ancestor","Gene family","Phylogenetics","Imaginal disc","Phenotype","Transcription factor","Embryogenesis","Genome"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"uniprot"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T03:42:11.416707Z","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":[]}