20.500.12556/RUL-175315 Mutual suppression between mutations in the Dictyostelium Greenbeard pathway restores wild-type development Background The Dictyostelium greenbeard pathway is mediated by two polymorphic transmembrane proteins,the TgrC1 ligand and the TgrB1 receptor. These proteins mediate allorecognition, altruism, and the developmental transition to multicellularity. A genetic suppressor screen revealed activating mutations in tgrB1 and inactivating mutations in rapgapB, a regulator of the GTPase protein RapA. Inactivation of either tgrB1, tgrC1, or rapgapB leads to developmental defects, but the respective double-mutant strains rapgapB$^–$tgrB1$^–$ and rapgapB$^–$tgrC1$^–$ develop well and produce spores. This mutual suppression could result from inducing an alternative pathway or from restoring wild-type development, but morphological analyses alone could not resolve this question. Results Here, we show that the mutual suppression between rapgapB$^–$ and tgrB1$^–$ restores wild-type development. We also analyzed an activated tgrB1 allele in the wild-type background and found evidence for interactions between the wild-type and the activated alleles. Using RNA-sequencing analyses, we compared the transcriptomes of the wild type to those of several mutant strains and found that the single-gene mutations attenuated transcriptome progression over developmental time, whereas the double-gene mutation strain rapgapB$^–$tgrB1$^–$ and the activated tgrB1 mutation exhibited near wild-type transcriptomes. Our findings suggest that tgrB1, tgrC1, and rapgapB are involved in a pathway in which rapgapB negatively regulates tgrB1 and tgrC1 expression, whereas tgrB1 and tgrC1 positively regulate rapgapB expression. Conclusions These findings suggest that the Dictyostelium greenbeard pathway interfaces with the central RapGAPB-RapA regulatory pathway, providing molecular insight into a mutual suppression mechanism in which two deleterious mutations restore wild-type behavior. greenbeard pathway mutual suppression transcriptome data analysis genska pot zelene brade medsebojna genska inhibicija analiza transkriptomskih podatkov true false true Angleški jezik Slovenski jezik Članek v reviji 2025-10-24 08:07:44 2025-10-24 08:07:44 2025-12-10 03:31:38 0000-00-00 00:00:00 2025 0 0 13 str. art. 563 Vol. 26 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.21:579.253.4 1471-2164 10.1186/s12864-025-11745-0 242854915 RAZ_Katoh-Kurasawa_Mariko_2025.pdf RAZ_Katoh-Kurasawa_Mariko_2025.pdf 1 3C4E0805EC2139278013BBB7298C908E aa8695417a7ca36035cf248a622656da5c8b670d1ae77098cf71f55b334d3a5f 77a5c553-b0a5-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=220780 https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-025-11745-0 1 7806cf7c-b09f-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=220762 Fakulteta za računalništvo in informatiko 0 0 0