title: Impact of migration and fitness on the stability of lethal t-haplotype polymorphism in Mus musculus: a computer study.
abstract: The t-haplotype is a chromosomal region in Mus musculus characterized by meiotic drive such that heterozygous males transmit t-bearing chromosomes to roughly 90% of their offspring. Most naturally occurring t-haplotypes express a recessive embryonic lethality, preventing fixation of the t-haplotype. Surprisingly, the t-haplotype occurs in nature as a persistent, low-frequency polymorphism. Early modeling studies led LEWONTIN to hypothesize that this low level polymorphism results from a balance between genetic drift in small demes and interdemic migration. Here, we show that while combination of deme size and migration rate that predict natural t-haplotype frequencies exist, the range of such values is too narrow to be biologically plausible, suggesting that small deme size and interdemic migration alone do not explain the observed t-haplotype frequencies. In response, we tested other factors that might explain the observed t-polymorphism. Two led to biologically plausible models: substantially reduced heterozygous fitness and reduced meiotic drive. This raises the question whether these phenomena occur in nature. Our data suggest an alternative explanation: there is no stable, low-level t-polymorphism. Rather wild populations are in one of two stable states characterized by extinction of the t-haplotype and a high t-haplotype frequency, respectively, or in transition between the two.
authors.affiliation: University of Pennsylvania, Computational Biology Group, Philadelphia 19104-6228, USA. durand@saul.cis.upenn.edu
authors.forename: D
authors.initials: D
authors.lastname: Durand
authors.forename: K
authors.initials: K
authors.lastname: Ardlie
authors.forename: L
authors.initials: L
authors.lastname: Buttel
authors.forename: S A
authors.initials: SA
authors.lastname: Levin
authors.forename: L M
authors.initials: LM
authors.lastname: Silver
mesh_terms: D000483:Alleles; D000818:Animals; D003198:Computer Simulation; D005260:Female; D005787:Gene Frequency; D005804:Genes, Lethal; D006239:Haplotypes / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice / Q000235:genetics*; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases