{"doi":"10.1073/pnas.2513676122","title":"Sharks and rays have the oldest vertebrate sex chromosome with unique sex determination mechanisms","abstract":"<jats:p>Sex determination has been investigated across vertebrate lineages to reveal the stepwise evolution of sex chromosomes and the diversity of responsible molecular mechanisms. However, these studies rarely include cartilaginous fishes, which diverged from the other vertebrates 450 Mya, hindering the comprehensive view of vertebrate sex determination. Here, we produced chromosome-scale genome assemblies of egg-laying shark species and comparatively investigated genome sequences and transcriptome profiles across diverse cartilaginous fishes. Sex chromosome identification, supported by cytogenetic experiments, elucidated the homology of X chromosomes between sharks and rays as well as an extensively degenerated Y chromosome harboring no detectable male-specific genes. Orthologs of documented sex-determining genes were identified, but not on these sex chromosomes. Transcriptomic analyses combined with histology of embryonic gonads revealed female-biased expression of X-linked genes—including those implicated in the TGF-β and IGF signaling pathways—attributed to incomplete dosage compensation. Our findings indicate that sharks and rays share the oldest sex chromosomes among vertebrates that originated around 300 Mya and the dosage-dependent sex determination mechanism composed of distinct molecules from other vertebrates. This study highlights the antiquity of sex chromosomes and the uniqueness of sex determination mechanisms in sharks and rays, which advances our understanding of evolutionary plasticity in vertebrate sex determination.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":670837,"datarank":0.4010498417059804,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.028313844237780286,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.028313844237780286,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":3,"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":186398,"name":"Yoshinobu Uno","orcid":null,"position":1,"is_corresponding":false},{"id":1669072,"name":"Yuta Ohishi","orcid":null,"position":2,"is_corresponding":false},{"id":334243,"name":"Mitsutaka Kadota","orcid":"0000-0002-1674-6697","position":3,"is_corresponding":false},{"id":1752405,"name":"Naotaka Aburatani","orcid":null,"position":4,"is_corresponding":false},{"id":1752407,"name":"Itsuki Kiyatake","orcid":null,"position":5,"is_corresponding":false},{"id":1752409,"name":"Daiki Katooka","orcid":null,"position":6,"is_corresponding":false},{"id":1752410,"name":"Michikazu Yorozu","orcid":null,"position":7,"is_corresponding":false},{"id":1752411,"name":"Nobutaka Tsuzuki","orcid":null,"position":8,"is_corresponding":false},{"id":14518,"name":"Atsushi Toyoda","orcid":"0000-0002-0728-7548","position":9,"is_corresponding":false},{"id":1752412,"name":"Wataru Takagi","orcid":"0000-0002-7882-0223","position":10,"is_corresponding":false},{"id":1752413,"name":"Masaru Nakamura","orcid":null,"position":11,"is_corresponding":false},{"id":658729,"name":"Shigehiro Kuraku","orcid":"0000-0003-1464-8388","position":12,"is_corresponding":false},{"id":1616826,"name":"Taiki Niwa","orcid":"0000-0002-5907-1431","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Sharks and rays have the oldest vertebrate sex chromosome with unique sex determination mechanisms","abstract":"<jats:p>Sex determination has been investigated across vertebrate lineages to reveal the stepwise evolution of sex chromosomes and the diversity of responsible molecular mechanisms. However, these studies rarely include cartilaginous fishes, which diverged from the other vertebrates 450 Mya, hindering the comprehensive view of vertebrate sex determination. Here, we produced chromosome-scale genome assemblies of egg-laying shark species and comparatively investigated genome sequences and transcriptome profiles across diverse cartilaginous fishes. Sex chromosome identification, supported by cytogenetic experiments, elucidated the homology of X chromosomes between sharks and rays as well as an extensively degenerated Y chromosome harboring no detectable male-specific genes. Orthologs of documented sex-determining genes were identified, but not on these sex chromosomes. Transcriptomic analyses combined with histology of embryonic gonads revealed female-biased expression of X-linked genes—including those implicated in the TGF-β and IGF signaling pathways—attributed to incomplete dosage compensation. Our findings indicate that sharks and rays share the oldest sex chromosomes among vertebrates that originated around 300 Mya and the dosage-dependent sex determination mechanism composed of distinct molecules from other vertebrates. This study highlights the antiquity of sex chromosomes and the uniqueness of sex determination mechanisms in sharks and rays, which advances our understanding of evolutionary plasticity in vertebrate sex determination.</jats:p>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":3,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40694337","pmcid":"PMC12318234","openalex_id":"https://openalex.org/W4412570098","authors":[],"funders":[{"funder_name":"MEXT | Japan Society for the Promotion of Science","grant_id":"20H03269","title":null},{"funder_name":"MEXT | Japan Society for the Promotion of Science","grant_id":"16H06279","title":null},{"funder_name":"MEXT | Japan Society for the Promotion of Science","grant_id":"21K06286","title":null},{"funder_name":"MEXT | Japan Society for the Promotion of Science","grant_id":"23KJ1002","title":null}],"total_grants":4,"fwci":10.4515,"citation_percentile":0.98642745,"influential_citations":0,"citation_trend":[{"year":2025,"count":5},{"year":2026,"count":6}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1073/pnas.2513676122","host_type":"journal"},{"url":"https://doi.org/10.1073/pnas.2513676122","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2513676122","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40694337","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12318234/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12318234","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12318234?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities","Reproductive biology and impacts on aquatic species","Gender Studies in Language"],"mesh_terms":["Animals","Female","Male","Sex Chromosomes","Sharks","Skates, Fish","Genome","Evolution, Molecular","Sex Determination Processes","Transcriptome"],"keywords":["Biology","Vertebrate","Dosage compensation","Evolutionary biology","Genome","X chromosome","Genetics","Gene","Chromosome","Autosome","X-inactivation","Sex determination","Vertebrate Evolution","Cartilaginous Fishes","Sex Chromosome Evolution"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life below water"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.31828447.v1","title":"Sequences used in molecular phylogeny reconstruction in Niwa et al., PNAS 2026","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.31828447.v2","title":"Sequences used in molecular phylogeny reconstruction in Niwa et al., PNAS 2025","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.31828447","title":"Sequences used in molecular phylogeny reconstruction in Niwa et al., PNAS 2025","publisher":"figshare","resource_type":"Dataset"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T00:10:42.833744Z","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":[]}