| First Author | Hammer M | Year | 1988 |
| Journal | Mouse News Lett | Volume | 82 |
| Pages | 113 | Mgi Jnum | J:14226 |
| Mgi Id | MGI:62399 | Citation | Hammer M, et al. (1988) t haplotype function, evolution and population dynamics. Mouse News Lett 82:113 |
| abstractText | Full text of MNL contribution: M. Hammer, S, Islam, J. Cebra-Thomas, J. Brown, S. Pilder, J.-Y. Tsai, K. Bibbins and L.M. Silver. Department of Molecular Biology, Princeton University, Princeton, NJ 08544 USA. t haplotyp-es are variant forms of chromosome 17 that have evolved the ability to propagate themselves through wild populations, by the inactivation of their wild-type spermatogenic partners. We will report investigations into the genetic, molecular, and physiological bases for this effect. We will also present data on the evolution of t haplotypes relative to other forms of mouse chromosome 17. Finally, we will present results of computer simulations of populations that contain t haplotypes. We have characterized a gene family (T66) that co-localizes with the t complex responder (Tcr) locus and is expressed uniquely in male germ cells. At least 3 members of this gene family are expressed from both wild-type and t haplotype forms of chromosome 17 with putative gene products that range in size from 45 to 50 kilodaltons. Nucleotide and amino acid differences are observed among all of the genes and alleles of this family. We have injected in vitro-produced T66 proteins into rabbits for the production of antisera that will be used to localize and characterize the T66 proteins in the mouse testes. The T66 gene family is conserved between mice and humans where it maps in linkage with other loci homologous to t complex proximal-region genes. We have compared the genetic organization of chromosome 17 from a series of related mouse species and from t haplotypes. Our data indicate that the most proximal portion of chromosome 17 (encompassing the loci of T , qk and Tcp-1) underwent an inversion in a common ancestor to the highly commensal species (M. domesticus and M. rnusculus). M. spretus and t haplotypes have the same ancestral genetic organization in this region allowing for free recombination between these two forms of chromosome 17. We have also used DNA sequencing and pseudo-sequencing (by 4-cutter analysis) to analyze the phylogenetic relationships that exist among alleles at several loci within the various forms of this chromosome. These and other data to be presented have major implications for our understanding of the selective forces responsible for the evolution of t haplotypes. In order to better understand the structure of mouse populations and the dynamics of t haplotype flow through these populations, a computer simulation has been developed (in the language C) in which one or more t haplotypes with particular properties of distortion and viability can be placed into populations of 100 or more demes with adjustable levels of inter-demic migration simulated through a poisson function. It is possible to account for all empirically observed frequencies of t haplotypes by adjusting the migration rate. Our simulation indicates that two complementing t haplotypes will never be maintained in a single population. Furthermore, our data indicate that mutations that cause either decreased homozygous viability or increased levels of distortion will be under strong positive selection. |
