9.B.459. The Mitotic Driver, Wtf (Wtf) Family Ubiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast Wtf meiotic drivers. They promote unequal transmission of alleles from the parental zygote to progeny spores by acting as a poison/antidote system where the poison and antidote proteins are produced from the same locus; the poison component is trans-acting and targets all spores within an ascus whereas the antidote component is spore-specific, leading to poisoning of all progeny that do not inherit the allele (Nuckolls et al. 2017). Post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs (Zheng et al. 2023). Isoform 1 localizes isoform 2 to the vacuole thereby facilitating its degradation. {Nuckolls et al. 2020). Isoform 2 forms toxic aggregates that disrupt spore maturation. {ECO:0000269\| (Bravo Núñez et al. 2020). The two isoforms can interact with each other and with themselves (Nuckolls et al. 2020). High sequence similarity is required for their interaction.
References:
Bravo Núñez, M.A., I.M. Sabbarini, L.E. Eide, R.L. Unckless, and S.E. Zanders. (2020). Atypical meiosis can be adaptive in outcrossed due to meiotic drivers. Elife 9:.
Nuckolls, N.L., A.C. Mok, J.J. Lange, K. Yi, T.S. Kandola, A.M. Hunn, S. McCroskey, J.L. Snyder, M.A. Bravo Núñez, M. McClain, S.A. McKinney, C. Wood, R. Halfmann, and S.E. Zanders. (2020). The meiotic driver utilizes controlled protein aggregation to generate selective cell death. Elife 9:.
Nuckolls, N.L., M.A. Bravo Núñez, M.T. Eickbush, J.M. Young, J.J. Lange, J.S. Yu, G.R. Smith, S.L. Jaspersen, H.S. Malik, and S.E. Zanders. (2017). genes are prolific dual poison-antidote meiotic drivers. Elife 6:.
Zheng, J.X., T.Y. Du, G.C. Shao, Z.H. Ma, Z.D. Jiang, W. Hu, F. Suo, W. He, M.Q. Dong, and L.L. Du. (2023). Ubiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast wtf meiotic drivers. Nat Commun 14: 8334.
Examples:
TC#	Name	Organismal Type	Example
9.B.459.1.1	Meiotic driver Wtf4 of 337 aas and 7 TMSs. (see family description for details.)		Wtf4 of Schizosaccharomyces kambucha

9.B.459.1.2	Meiotic drive suppressor Wtf23 of 336 aas and 6 or 7 TMSs.		Wft23 of Schizosaccharomyces pombe

9.B.459.1.3	Mitotic driver, Wtf of 260 aas and 5 TMSs. It is probably an incomplete sequence.		Wtf of Schizosaccharomyces osmophilus

9.B.459.1.4	Wtf mitotic driver of 263 aas and 4 TMSs; it's probably truncated.		Wtf if Schizosaccharomyces osmophilus