Nucleotide sequence of mouse Tcp-1a cDNA.

Area of Science:

• Molecular Biology
• Genetics
• Evolutionary Biology

Background:

• The t-complex in mice is a region of the genome associated with male sterility and developmental abnormalities.
• TCP-1 (t-complex polypeptide 1) is a molecular chaperone involved in protein folding.

Purpose of the Study:

• To isolate and characterize complete cDNA clones for mouse t-complex polypeptides 1A and 1B (TCP-1A and TCP-1B).
• To compare the nucleotide and amino acid sequences of Tcp-1a and Tcp-1b alleles.
• To investigate the evolutionary rate of amino acid substitution in TCP-1.

Main Methods:

• Isolation of complete cDNA clones encoding TCP-1A and TCP-1B from t-haplotype and wild-type mice.
• Determination of the complete nucleotide sequence of the Tcp-1a cDNA.
• Comparative analysis of nucleotide sequences and open reading frames between Tcp-1a and Tcp-1b cDNAs.

Main Results:

• Complete cDNA clones for mouse TCP-1A and TCP-1B were successfully isolated.
• The Tcp-1a cDNA contains an open reading frame encoding a 60-kDa protein of 556 amino acids.
• Significant differences were observed in the non-coding regions and polyadenylation sites between Tcp-1a and Tcp-1b.
• Fifteen base pair substitutions within the open reading frames resulted in eleven amino acid substitutions between the alleles, with twelve being nonsynonymous.
• Amino acid substitution rates in TCP-1 are approximately 20 times higher between t-haplotype and wild-type mice than between mouse and human or mouse and Drosophila.

Conclusions:

• The study provides detailed molecular characterization of mouse TCP-1A and TCP-1B.
• Sequence comparisons reveal substantial allelic variation within the mouse TCP-1 gene.
• The accelerated rate of amino acid substitution in TCP-1 between t-haplotype and wild-type mice suggests strong diversifying selection or rapid evolution in this region.