{"doi":"10.1101/2024.03.27.586985","title":"Evolutionary divergence between homologous X-Y chromosome genes shapes sex-biased biology","abstract":"ABSTRACT Sex chromosomes are a fundamental aspect of sex-biased biology, but the extent to which homologous X–Y gene pairs (“the gametologs”) contribute to sex-biased phenotypes remains hotly-debated. Although these genes exhibit large sex differences in expression throughout the body (XX females express both X members; XY males express one X and one Y member), there is conflicting evidence regarding the degree of functional divergence between the X and Y gametologs. Here, we use co-expression fingerprint (CF) analysis to characterize functional divergence between the X and Y members of 17 gametolog gene pairs across >40 human tissues. Gametologs exhibit functional divergence between the sexes that is driven by divergence between the X vs. Y gametologs (assayed in males) and is greatest among evolutionary distant gametolog pairs. These patterns reflect that X vs. Y gametologs show coordinated patterns of asymmetric coupling with large sets of autosomal genes, which are enriched for functional pathways and gene sets implicated in sex-biased biology and disease. These findings suggest that the X and Y gametologs have diverged in function, and prioritize specific gametolog pairs for future targeted experimental studies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486889,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1330979,"name":"Kathryn Tsai","orcid":null,"position":1,"is_corresponding":false},{"id":232628,"name":"Siyuan Liu","orcid":"0000-0003-3661-6248","position":2,"is_corresponding":false},{"id":944620,"name":"Adam Thomas","orcid":null,"position":3,"is_corresponding":false},{"id":232635,"name":"Armin Raznahan","orcid":"0000-0002-5622-1190","position":4,"is_corresponding":false},{"id":409055,"name":"Alex R. DeCasien","orcid":"0000-0002-6205-5408","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:01.404471Z","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":[]}