Average locus differences in mutability related to protein "class": a hypothesis.

Abstract

Substantially less genetic variation has been recognized in studies of the proteins of nucleated cells by the technique of two-dimensional polyacrylamide gel electrophoresis than has been encountered in studies of serum transport proteins and erythrocyte enzymes with one-dimensional electrophoresis. Technical factors appear to account for only part of the difference. The two remaining (nonexclusive) explanations are more stringent biological selection against variants of these proteins or lower mutation rates at the loci encoding the proteins visualized with two-dimensional electrophoresis. While the former possibility cannot be rigorously excluded, the evidence suggests the latter hypothesis merits serious consideration. Some consequences of this latter suggestion for genetic monitoring and the interpretation of molecular evolution are mentioned.

Similarity of spontaneous germinal and in vitro somatic cell mutation rates in humans: implications for carcinogenesis and for the role of exogenous factors in "spontaneous" germinal mutagenesis.

“…Fifth, mutations do not occur at random throughout the genome. Spontaneous germ-line nucleotide mutation rates in humans appear to vary between loci by a factor of at least 16 (12,21). There is also evidence for wide variation in humans in the rate of nucleotide substitutions induced by ethylnitrosourea (26).…”

“…However, based on studies of known variants in the two systems, we doubt that the failure to detect variants with 2-D PAGE under the conditions employed could account for more than a 10% difference between the two series (20). (iii) The mutability of the relatively small subset of proteins examined with 1-D electrophoresis might not be comparable to that of the larger number of proteins examined by 2-D PAGE (21). (iv) The approach assumes equal survival of mutations causing nucleotide substitutions in these somatic cells in culture and similar mutations in the human germ line.…”

Two-dimensional electrophoresis of proteins as a source of monogenic and codominant markers for population genetics and mapping the expressed genome

“…The species analysed were taxonomically diverse, including two monocotyledons, one dicotyledon and one gymnosperm, making the results of probable general value. In addition to technical improvements (Rosenblum et a!., 1983;Damerval et a!., 1986), there would be at least three reasons for these relatively 'high' levels of polymorphism: (1) 2-D PAGE does not only reveal unit charge substitutions, but also other variations not detectable by 1-D PAGE (discussed by Neel, 1990); (2) in contrast with previous results (e.g. Singh & Coulthart, 1982), neither the insolubility nor the abundance of the polypeptides seem to be factors decreasing the variability, at least in maize (Damerval, 1994); (3) the majority of proteins revealed are not structural ones: partial sequencing of 36 major proteins excised from the gels has shown that most of the significant homologies are with enzymes (P. Touzet, in preparation).…”

Genetic variability of the marine mussel Mytilus galloprovincialis assessed using two-dimensional electrophoresis

“…This suggests that 2-DE could have a great potential for the study of genetic variability of populations, in that it allows a more representative sample of the genome to be analysed. However, studies of genetic variability in natural populations of animal species by means of 2-DE have been relatively scarce, because 2-DE is technically more difficult and time consuming than 1-DE and, furthermore, because the first results revealed substantially less genetic variation than had been estimated by 1-DE (Edwards and Hopkinson, 1980;Aquadro and Avise, 1981;Neel, 1990). Moreover, most studies have been focused on a few species (particularly man and Drosophila) so that the available information is to a large extent redundant and biased as a means of getting an appropriate view of the levels of genetic variability detected by 2-DE.…”