The rate with which spontaneous mutation alters the electrophoretic mobility of polypeptides.

Abstract

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 per locus per generation. The apriori 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 per locus per generation. Since electrophoresis only detects about half of the amino acid substitutions due to mutations of nucleotides, the corrected rate for mutations causing amino acid substitutions in polypeptides is 1.2 x i0-5 per locus per 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 =1.8 x 10-5 per locus per generation. When the present observations are combined with all of the other available data concerning mutation resulting in electrophoretic variants, the electrophoretic rate drops to 0.3 x 10-5 per locus per generation, the total locus rate drops to roughly 1.0 x 10-5, and the nucleotide rate drops to 1 x 10-8. Even with this lower estimate, given -2 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 -20 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.In a previous report in these PROCEEDINGS we have described the protocol and the preliminary results of a search for mutations altering the electrophoretic behavior of a series of proteins, in children of atomic bomb survivors and a suitable group of control children (1). This study has now been completed. In the present report we describe the spontaneous mutation rate observed in the so-called control children of that study-i.e., children both of whose parents were more than 2500 meters from the hypocenter at the time of the bombings or one ofwhose parents was at this distance and the other was not in the city. These parents, referred to as the distally exposed, are presumed to have received either no radiation, or very negligible amounts (<1 rad; 1 rad = 0.01 gray), at the time of the bombings (ATB). In a few instances, neither of the parents in the control group was in the city ATB. These data are combined with other similar data available from the world literature to obtain a best estimate of the rate with which mutation results in electrophoretic variants and to infer both the total rate with which mutation results in an amino acid substitution in proteins and the nucleotide mutation rate to which this corresponds. Whenever a rare variant was encountered, an effort was made to obtain a blood sample from both the f...

Time for acquiring a new gene by duplication.

“…According to Kimura (14), Nvo is often in the range from 0.01 to 0.05. This agrees with values directly estimated for enzyme loci (15)(16)(17). As for deteriorating mutation, two cases were examined: in one case v = vo + v+ and in the other case v -= 0.…”

Description and validation of a method for simultaneous estimation of effective population size and mutation rate from human population data.

“…ref. 31), we would now be somewhat more cautious in any precise estimate of the total mutation rates than previously.…”

Investigation of Human Protein Variants and Their Frequency in the General Population

“…Thus, we can assume that the data obtained in this study represent the normal distribution of these protein modifications in the general United States population. This systematic study of protein modifications and variants using MS methods of detection is the first of its kind; past large scale studies of variations at the protein level have relied on electrophoretic techniques (16). Recent human diversity studies at the genome level have helped redefine the "normal" human genome (17,18) and have identified human genes that are mutated in cancer (19).…”