Mammalian Genome 2:246-251, 1992 9 Springer-Verlag New York Inc. 1992 Nucleotide sequence of a mouse Tcp-1 pseudogene: A nucleotide record for a t complex gene carried by an ancestor of the mouse Hiroshi Kubota, 1 Takashi Morita, 1 Yoko Satta, 2 Masami Nozaki, 1 and Aizo Matsushiro 1 1Department of Microbial Genetics, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka 565, Japan; 2National Institute of Genetics, Yata 1-111, Mishima, Shizuoka 411, Japan Received July 9, 1991; accepted September 9, 1991 Abstract. We have isolated clones of a processed pseudogene of mouse t complex polypeptide 1 (Tcp-1) and determined the nucleotide sequence of the pseudogene. The pseudogene was 1363 bp long and had no intron. The Tcp-1 pseudogene had 88.4% or 88.3% nucleotide identity to the mouse Tcp-1 cDNA of wild-type (Tcp-1 b) or t haplotype (Tcp-U), and 87.5% identity to the rat Tcp-1 cDNA. On 12 nucleotide po- sitions where the open reading frames (ORFs) of mouse Tcp-1 b and Tcp-U cDNAs have bp substitu- tions, the Tcp-1 pseudogene had 6 bp identical to Tcp- 1b, 5 bp identical to Tcp-U and 1 bp not identical to neither. On ten amino acid positions where TCP-1B and TCP-1A polypeptides have substitutions, deduced amino acids of the Tcp-1 pseudogene had four amino acids identical to TCP-1B, five amino acids identical to TCP-1A and one amino acid identical to neither. These results suggest that the ancestral mouse Tcp-1 gene would have had no significant difference between the resemblance to Tcp-t ~ and that to Tcp-I ~ before they were diverged and that amino acids of TCP-1B and TCP-1A would have been substituted in similar high rates. Introduction Mouse t haplotypes (reviewed by Silver 1985; Com- mittee for Mouse Chromosome 17 1991) have four large inversions on Chromosome (Chr) 17 (Hammer et The nucleotide sequence data reported in this paper have been sub- mitted to GenBank and have been assigned the accession number D00851. Offprint requests to: T. Morita al. 1989) which may explain the recombination sup- pression between the t haplotype and wild-type. The t haplotypes widely spread in wild populations at t~+ heterozygous state (Klein et al. 1984; Ruvinsky et al. 1991), while most homozygous t haplotype mice die during embryonic development. The spread is thought to depend on the transmission ratio distortion (TRD) which transmit the t haplotype ten to a hundred times more frequently than wild-type from the t/+ male to its descendants (Lyon 1984). The t haplotypes have been suggested to be derived from a recent single an- cestral chromosome (Nizetic et al. 1984; Silver et al. 1987b) 1-2 million years ago (Frischauf 1985; Willison et al. 1986). Mouse Tcp-1 is a gene located in the t complex and encodes t complex polypeptide 1 (TCP-1) which is in- volved in an intracellular transport system (Willison et al. 1989). The TCP-I protein has t haplotype specific form (TCP-1A) and wild-type specific form (TCP-B; Silver et al. 1979; Willison et al. 1986). These proteins are expressed at a high level during spermatogenesis (Silver et al. 1987a) and also at lower levels in almost all cells investigated. Nucleotide sequences of Tcp-1 b and Tcp-I a cDNAs were reported (Willison et al. 1986; Kirchhoff and Willison 1990; Kubota et al. 1991). The comparison between the Tcp-1 b and Tcp-U cDNAs indicated a very high rate of amino acid substitutions between TCP-1B and TCP-1A (Kubota et al. 1991). Previous investigators have suggested that the an- cestral Tcp-1 gene of mice might more closely resem- ble Tcp-1 a than Tcp-I b (Willison et al. 1987; Delarbre et al. 1988; Ursic and Ganetzky 1988). Here, we de- termined the nucleotide sequence of a mouse Tcp-1 pseudogene and compared the sequence and deduced amino acids to those of Tcp-1 cDNAs of mouse t hap- lotype and wild-type, rat and human. From the com- parison, we discuss the molecular evolution of the t haplotype and wild-type Tcp-1 genes.