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Negative Complementation
1302
N e g a t i ve Co mp lem en ta tio n
deleterious, and most mutations with small effects are likely to be slightly deleterious. Such mutations are selected against in large populations, but behave as if neutral in small populations. They are called nearly neutral mutations, and entail a negative correlation between evolutionary rate and population size. Quantitative treatment may be pursued in terms of the principle that the rate of gene substitution equals the number of new mutations multiplied by their fixation probability. An important prediction of the nearly neutral theory is related to the molecular clock of amino acid substitution, which is dependent on the chronological time rather than on the generation number. Mutation rate depends on the number of cell generations, and DNA regions without genetic information should evolve directly reflecting the generation number. As an empirical observation, large organisms with long generation time tend to have small population size and vice versa. Then, under the nearly neutral theory, the generation-time effect of mutation rate partially cancels the population-size effect of fixation probability. On the other hand, for DNA regions without genetic information, such cancellation is not predicted. The prediction was tested by comparing the patterns of synonymous and nonsynonymous substitutions. Forty-nine gene sequences of three orders, primate, artiodactyl and rodent, were analyzed. The results show that the generation-time effect is more conspicuous for synonymous substitutions than for nonsynonymous substitutions, i.e., the rodent branch is much longer than the primate branch for synonymous changes, but the difference of the two branches is not so large for nonsynonymous ones. Primates generally have longer generation times, and the difference in the patterns of the two types is consistent with the nearly neutral theory.
Population Genetic Studies Data on DNA polymorphisms within populations are rapidly accumulating. Under the neutral theory, most polymorphisms are phases of gene substitution, and quantitative predictions can be made. Again, by separately measuring synonymous and nonsynonymous polymorphisms, some departures from the neutral prediction were reported. As an alternative to the neutral theory, it is often difficult to discriminate between the selection theory and the nearly neutral theory. This is because various patterns of polymorphisms may be explained under both theories. For example, if the selection coefficient of a nearly neutral mutant differs in the opposite direction between local colonies, and migration is limited, the very weak selection would be effective in maintaining
polymorphisms, and it is difficult to distinguish it from balancing selection. With the progress of the genome diversity project, data on DNA polymorphisms are rapidly accumulating. Data revealed prevalence of slightly deleterious or nearly neutral amino acid substitutions again by comparing the patterns of synonymous and nonsynonymous single nucleotide polymorphisms. Precise formulation of the nearly neutral theory is difficult. Much depends on the assumption of the fitness distribution of mutations. Epistatic interaction at various levels, such as among amino acid sites within a protein and between regulatory regions of DNA and proteins, is another important factor that needs to be studied in shaping the nearly neutral model. Variation of evolutionary rate of proteins, which was found to be too large to the neutral prediction, reflects such interactive systems. Although there are differences between the neutral and the nearly neutral theories, some scientists use the former term to include the latter. This is because random drift is the driving force in both theories. It is suggested here that the nearly neutral theory should be used as it is in professional discussions. However in general discussions, the neutral theory in the broad sense may include both theories. In particular, selective neutrality usually means the set of all mutations around strict neutrality. See also: Epistasis; Fixation Probability; Gene Substitution; Molecular Clock; Neutral Theory; Selective Neutrality
Negative Complementation Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1922
Negative complementation refers to interallelic complementation where a mutant subunit suppresses the activity of a wild-type subunit in a multimeric protein. See also: Complementation
Negative Interference F W Stahl Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0888
In the recombination of linked markers, the coefficient of coincidence (C) measures the degree of correlation
N e g a t i ve Co mp lem en ta tio n
deleterious, and most mutations with small effects are likely to be slightly deleterious. Such mutations are selected against in large populations, but behave as if neutral in small populations. They are called nearly neutral mutations, and entail a negative correlation between evolutionary rate and population size. Quantitative treatment may be pursued in terms of the principle that the rate of gene substitution equals the number of new mutations multiplied by their fixation probability. An important prediction of the nearly neutral theory is related to the molecular clock of amino acid substitution, which is dependent on the chronological time rather than on the generation number. Mutation rate depends on the number of cell generations, and DNA regions without genetic information should evolve directly reflecting the generation number. As an empirical observation, large organisms with long generation time tend to have small population size and vice versa. Then, under the nearly neutral theory, the generation-time effect of mutation rate partially cancels the population-size effect of fixation probability. On the other hand, for DNA regions without genetic information, such cancellation is not predicted. The prediction was tested by comparing the patterns of synonymous and nonsynonymous substitutions. Forty-nine gene sequences of three orders, primate, artiodactyl and rodent, were analyzed. The results show that the generation-time effect is more conspicuous for synonymous substitutions than for nonsynonymous substitutions, i.e., the rodent branch is much longer than the primate branch for synonymous changes, but the difference of the two branches is not so large for nonsynonymous ones. Primates generally have longer generation times, and the difference in the patterns of the two types is consistent with the nearly neutral theory.
Population Genetic Studies Data on DNA polymorphisms within populations are rapidly accumulating. Under the neutral theory, most polymorphisms are phases of gene substitution, and quantitative predictions can be made. Again, by separately measuring synonymous and nonsynonymous polymorphisms, some departures from the neutral prediction were reported. As an alternative to the neutral theory, it is often difficult to discriminate between the selection theory and the nearly neutral theory. This is because various patterns of polymorphisms may be explained under both theories. For example, if the selection coefficient of a nearly neutral mutant differs in the opposite direction between local colonies, and migration is limited, the very weak selection would be effective in maintaining
polymorphisms, and it is difficult to distinguish it from balancing selection. With the progress of the genome diversity project, data on DNA polymorphisms are rapidly accumulating. Data revealed prevalence of slightly deleterious or nearly neutral amino acid substitutions again by comparing the patterns of synonymous and nonsynonymous single nucleotide polymorphisms. Precise formulation of the nearly neutral theory is difficult. Much depends on the assumption of the fitness distribution of mutations. Epistatic interaction at various levels, such as among amino acid sites within a protein and between regulatory regions of DNA and proteins, is another important factor that needs to be studied in shaping the nearly neutral model. Variation of evolutionary rate of proteins, which was found to be too large to the neutral prediction, reflects such interactive systems. Although there are differences between the neutral and the nearly neutral theories, some scientists use the former term to include the latter. This is because random drift is the driving force in both theories. It is suggested here that the nearly neutral theory should be used as it is in professional discussions. However in general discussions, the neutral theory in the broad sense may include both theories. In particular, selective neutrality usually means the set of all mutations around strict neutrality. See also: Epistasis; Fixation Probability; Gene Substitution; Molecular Clock; Neutral Theory; Selective Neutrality
Negative Complementation Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1922
Negative complementation refers to interallelic complementation where a mutant subunit suppresses the activity of a wild-type subunit in a multimeric protein. See also: Complementation
Negative Interference F W Stahl Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0888
In the recombination of linked markers, the coefficient of coincidence (C) measures the degree of correlation