Technical Report No. 7-87
The rate with which spontaneous mutation alters the electrophoretic mobility of polypeptides
Neel JV, Satoh C, Goriki K, Fujita M, Takahashi N, Asakawa J, Hazama RSummary
Studies of a Japanese population, involving a total of 539,170 locus tests distributed over 36 polypeptides, yielded three presumptive spontaneous mutations altering the electrophoretic mobility of the polypeptide. This corresponds to a mutation rate of 0.6 x 10-5/locus/generation. The a priori probability that undetected discrepancies between legal and biological parentage might in our test system result in an apparent electrophoretic mutation in this population is calculated to be only 0.3 x 10-7/locus/generation. Since electrophoresis only detects about half the amino acid substitutions due to mutations of nucleotides, the corrected rate for mutations causing amino acid substitutions in polypeptides is 1.2 x 10-5/locus/generation. With allowance for synonymous mutations and those resulting in stop codons, the total mutation rate for nucleotide changes in the exons encoding a polypeptide becomes approximately 1.8 x 10-5/locus/generation. When the present observations are combined with all the other available data concerning mutation resulting in electrophoretic variants, the electrophoretic rate drops to 0.3 x 10-5/locus/generation, the total locus rate to roughly 1.0 x 10-5, and the nucleotide rate to 1 x 10-8. Even with this lower estimate, given approximately 3 x 109 nucleotides in the haploid genome and an average of 103 exon nucleotides per polypeptide encoded, the implication, if these exon rates can be generalized, is of approximately 30 nucleotide mutations per gamete per generation. This estimate of the frequency of “point” mutations does not include small duplications, rearrangements, or deletions resulting from unequal crossing over, transcription errors, etc.
Studies of a Japanese population, involving a total of 539,170 locus tests distributed over 36 polypeptides, yielded three presumptive spontaneous mutations altering the electrophoretic mobility of the polypeptide. This corresponds to a mutation rate of 0.6 x 10-5/locus/generation. The a priori probability that undetected discrepancies between legal and biological parentage might in our test system result in an apparent electrophoretic mutation in this population is calculated to be only 0.3 x 10-7/locus/generation. Since electrophoresis only detects about half the amino acid substitutions due to mutations of nucleotides, the corrected rate for mutations causing amino acid substitutions in polypeptides is 1.2 x 10-5/locus/generation. With allowance for synonymous mutations and those resulting in stop codons, the total mutation rate for nucleotide changes in the exons encoding a polypeptide becomes approximately 1.8 x 10-5/locus/generation. When the present observations are combined with all the other available data concerning mutation resulting in electrophoretic variants, the electrophoretic rate drops to 0.3 x 10-5/locus/generation, the total locus rate to roughly 1.0 x 10-5, and the nucleotide rate to 1 x 10-8. Even with this lower estimate, given approximately 3 x 109 nucleotides in the haploid genome and an average of 103 exon nucleotides per polypeptide encoded, the implication, if these exon rates can be generalized, is of approximately 30 nucleotide mutations per gamete per generation. This estimate of the frequency of “point” mutations does not include small duplications, rearrangements, or deletions resulting from unequal crossing over, transcription errors, etc.