Concerted evolution of the mouse Tcp-10 gene family: Implications for the functional basis of t haplotype transmission ratio distortion

The mouse Tcr locus is defined by its central role in the transmission ratio distortion phenotype characteristic of t haplotypes. A molecular candidate for Tcr has been identified in the form of a gene— Tcp-10b—expressed during spermatogenesis. Tcp-10 b is one member of a multigene family present in two to four copies on different homologs of chromosome 17. The coding regions of the Tcp-10 genes present within two inbred strains were compared with those of the t ω5 haplotype. The various gene family members are highly conserved relative to each other with a minimum nucleotide identity of 98.6% in all pairwise comparisons. Maximal parsimony analysis indicates that the Tcp-10 gene family has evolved in a concerted manner with the obliteration of nearly all individual gene-specific characteristics. As a consequence, the candidate for the fulllength mutant Tcr gene product is distinguished by only a single, highly conservative, amino acid change. The data are consistent with the hypothesis that the effector of mutant Tcr activity is a second, alternatively spliced product that is expressed in a haploid- and allele-specific manner.