{"doi":"10.1101/2025.04.23.650085","title":"Cell division timing shapes the morphology and size of nascent multicellular organisms","abstract":"Upon making the transition from unicellularity to multicellularity, many previously optimized cellular traits experience the renewed scrutiny of natural selection due to their novel effects on emergent multicellular phenotypes. Yet we lack a comprehensive understanding of how and why specific cellular traits influence multicellular phenotypes and fitness. The snowflake yeast model system provides a tractable entry point for such investigations. The effects of several cell-level traits (cellular aspect ratio, cell volume, bud neck strength) on multicellular cluster size have been characterized, but we found that these properties were insufficient to explain the difference in cluster size between the two strains that serve as the ancestors of the ongoing Multicellularity Long-Term Evolution Experiment (MuLTEE). Using time-lapse microscopy and single cell tracking, we identified the timing of cell division as a cellular trait that strongly influences multicellular morphology and size in snowflake yeast. The \"petite\" ancestor divides asynchronously, with a 25% longer first division, while the \"grande\" ancestor divided synchronously. Using network theoretical and biophysical models, we showed that strains exhibiting a first division delay generate more highly-branched network topologies, accelerating the accumulation of crowding-induced mechanical stress, resulting in clusters that fracture at smaller sizes. Conversely, synchronously dividing strains produce more symmetric, larger clusters. Synchronous cell division can provide benefits through both faster growth and larger size, suggesting multiple potential selective pathways for its evolution. Furthermore, we explore how accelerated first division can produce even larger groups and how another unexpected mechanism for modifying cluster size, apoptosis rate, may interfere with these effects. Our results identify cell division timing as a previously underappreciated axis of phenotypic variation that strongly influences multicellular morphology. This suggests that temporal regulation of cell division represents an evolutionarily accessible mechanism for early control of morphogenesis in nascent multicellular organisms with permanent intercellular bonds.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":564801,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9472,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1161132,"name":"Rozenn M. Pineau","orcid":"0000-0003-0275-9080","position":1,"is_corresponding":false},{"id":806782,"name":"Thomas C. Day","orcid":"0000-0003-4681-9348","position":2,"is_corresponding":false},{"id":345629,"name":"William C. Ratcliff","orcid":"0000-0002-6837-8355","position":3,"is_corresponding":false},{"id":808167,"name":"Peter L. Conlin","orcid":"0000-0002-2793-7624","position":4,"is_corresponding":false},{"id":1468037,"name":"Luis F. Cedeño-Pérez","orcid":"0009-0008-4138-0851","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:24.872312Z","pmid":"42239451","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":[]}