Mutual suppression between mutations in the Dictyostelium Greenbeard pathway restores wild-type development

Katoh-Kurasawa, Mariko (author), Trnovec, Lena (author), Lehmann, Peter (author), Zupan, Blaž (author), Shaulsky, Gad (author)

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.

• Language: English
• Keywords: greenbeard pathway, mutual suppression, transcriptome data analysis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FRI - Faculty of Computer and Information Science
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 13 str.
• Numbering: Vol. 26, art. 563
• PID: 20.500.12556/RUL-175315
• UDC: 577.21:579.253.4
• ISSN on article: 1471-2164
• DOI: 10.1186/s12864-025-11745-0
• COBISS.SI-ID: 242854915
• Publication date in RUL: 24.10.2025

Record is a part of a journal

• Title: BMC genomics
• Shortened title: BMC Genomics
• Publisher: BioMed Central
• ISSN: 1471-2164
• COBISS.SI-ID: 2438420

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: genska pot zelene brade, medsebojna genska inhibicija, analiza transkriptomskih podatkov