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ScienceWeek
EVOLUTION: ON STATIONARY PHASE MUTATION RATES
The following points are made by Paul Sniegowski (Current Biology 2004 14:R245):
1) The genomic mutation rate is a fundamental evolutionary parameter of any population, determining the rate of influx of new deleterious and beneficial alleles. Because most mutations are likely to be harmful to fitness, DNA repair and proofreading systems have probably evolved so as to minimize rates of mutation [1]. Even the microbial extremophiles that normally inhabit harsh and potentially mutagenic environments seem to have low genomic mutation rates [2], suggesting that selection almost always puts a premium on the faithful maintenance and transmission of genetic information. Nonetheless, geneticists have long known that some environmental extremes can elevate mutation rates; indeed, this is the basis for the use of DNA damaging agents to induce mutations for study.
2) What has remained unclear is whether the range of natural environmental stresses encountered by organisms can also have a strong effect on mutation rates. Bacteria, in particular, may often find themselves in environments where cell division is arrested by resource limitation, and this raises the interesting possibility that exposure to such environments elevates the bacterial genomic mutation rate. A recent study by Loewe et al [3] supports this idea by finding that genomic mutation rates are higher when Escherichia coli cultures are held under prolonged growth arrest than when they are actively dividing.
3) To assay mutation rates in nongrowing E. coli cultures, Loewe et al [3] used the "mutation accumulation" approach developed from quantitative genetic theory [4,5]. In contrast to classical genetic methods that estimate rates of mutation by tracking changes at specific loci, mutation accumulation experiments use measurements of fitness or a phenotypic character closely related to fitness to estimate the rate at which deleterious mutations arise genome-wide. A mutation accumulation experiment is conducted by maintaining a set of initially isogenic replicate populations at low effective population size, so that new mutations persist regardless of their fitness effects.
4) Because almost all mutations are deleterious to fitness, absolute measures of mean fitness in the replicate populations decrease over time; because different numbers and combinations of mutations accumulate by chance in different replicate populations, the variance in fitness increases. The mean change in fitness over all populations, and the increase in the variance of fitness, can be used to estimate the deleterious genomic mutation rate.
References (abridged):
1. Drake, J.W., Charlesworth, B., Charlesworth, D., and Crow, J.F. (1998). Rates of spontaneous mutation. Genetics 148, 1667-1686
2. Grogan, D.W., Carver, G.T., and Drake, J.W. (2001). Genetic fidelity under harsh conditions: Analysis of spontaneous mutation in the thermoacidophilic archaeon Sulfolobus acidocaldarius. Proc. Natl. Acad. Sci USA 98, 7928-7933
3. Loewe, L., Textor, V., and Scherer, S. (2003). High deleterious mutation rate in stationary phase of Escherichia coli. Science 302, 1558-1560
4. Mukai, T. (1964). The genetic structure of natural populations of Drosophila melanogaster. I. Spontaneous mutation rate of polygenes controlling viability. Genetics 50, 1-19
5. Bateman, A.J. (1959). The viability of near-normal irradiated chromosomes. Int. J. Rad. Biol. 1, 170-180
Current Biology http://www.current-biology.com
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EVOLUTIONARY BIOLOGY: ON EVOLUTIONARY GENETICS
The following points are made by Guenter P. Wagner (Current Biology 2003 13:R958):
1) All life on Earth owes its existence to genetic accidents --mutations. Without genetic variation, no evolution would be possible and hence life as we know it would not exist. Also existing life forms would be doomed in the long run if there were not a steady stream of genetic novelties that allow species to adapt to changing environmental conditions, such as ice ages or global warming. Yet genetic variation is perhaps most intensely studied because it usually has negative effects. These effects attract our attention in the form of congenital diseases and disease susceptibilities. The study of the negative effects of genetic variation gave rise to the fields of genetic epidemiology and human medical genetics, which may now be the most intensely studied area of genetics.
2) Which provokes the question: In the face of a constant stream of deleterious genetic accidents, how does life continue? Decrease the mutation rate and run the risk of being unable to adapt to unforeseen environmental changes? Produce armies of offspring, in the hope that a few will have the right genes to survive and have children of their own? Neither of these seems to be the answer chosen by nature, at least not exclusively. Mutation rates are somewhat different between bacteria and eukaryotes, but among eukaryotes, the rates are not so different between "lower" and "higher" forms. More complex organisms, such as humans, tend to have fewer offspring than simpler forms, such as fungi. Hence a large number of offspring also does not seem to be the solution of choice.
3) A third solution to the problem of deleterious genetic variation was suggested by early genetic experiments. It was observed that a mutation with a major impact on a phenotypic character generally has two kinds of effects: there is its primary effect, changing the average appearance of the character; but there is also a secondary effect, as the mutant phenotype is also more variable than the wild type. A well studied example is the mutation /Scute/, which influences, among other things, the number of bristles on the back of the fruit fly [1]. Drosophila melanogaster usually has four bristles, with very rare deviations from this number. After the mutation /Scute/ is introduced, this number is increased, but also the amount of variation is many orders of magnitude higher than in the wild type.
4) Unexpectedly, the variation of the /Scute/ mutant phenotype turned out to be partly genetic. This is shown, for instance, by the way artificial selection leads to a strong response in the mutant populations, while having little, if any, effect on the average number of bristles in a wild-type population. Even though these experiments did not reveal the precise nature of the genetic variation, they undeniably demonstrated genetic variation for the character that is not expressed in the wild type, but becomes visible in the mutant background.
References (abridged):
1. Rendel, J.M. (1967). Canalization and Gene Control. (New York: Logos Press, Academic Press)
2. Dworkin, I., Palsson, A., Birdsall, K., and Gibson, G. (2003). Evidence that Egfr contributes to cryptic genetic variation for photoreceptor determination in natural populations of Drosophila. Curr. Biol. 13, 1888-1893
3. Waddington, C.H. (1957). The Strategy of the Genes. (New York: MacMillan Co.)
4. Scharloo, W. (1991). Canalization: Genetic and developmental aspects. Annu. Rev. Ecol. Syst. 22, 65-93
5. Stearns, S.C. and Kawecki, T.J. (1994). Fitness sensitivity and the canalization of life history traits. Evolution 48, 1438-1450
Current Biology http://www.current-biology.com
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EVOLUTIONARY BIOLOGY: ON MODULATING MUTATION RATES
The following points are made by S.M. Rosenberg and P.J. Hastings (Science 2003 300:1382):
1) In evolution, the environment selects the fittest genetic variants, but does it also provoke the generation of genetic variants? And if it does, can this speed up the rate of evolution? Both of these ideas have been supported by work on laboratory strains of bacteria and yeast over the past 15 years.
2) Bacterial cultures exposed to growth-limiting stress, such as starvation, sometimes produce mutants, apparently in response to stress (1). This process has been variously termed adaptive, stationary-phase, or stress-inducible mutation. In the best documented examples, both useful and deleterious mutations may arise. There seem to be multiple molecular mechanisms underlying stress-inducible mutagenesis, and some of these differ demonstrably from those causing spontaneous mutations in rapidly growing cells.
3) Controversy surrounds the question of whether any of these mechanisms was itself selected for its ability to produce genetic diversity, or whether all are by-products of error-prone DNA repair processes selected for their immediate survival value (or both). In addition, whether any of the assays using laboratory strains of bacteria reflect the biology of organisms in the real world has been a controversial subject. Some of these debates may be resolved by Bjedov et al (2), who provide support for stress-inducible mutagenesis in stationary-phase bacterial colonies grown from strains culled from the real world. The authors provide evidence that most natural isolates of Escherichia coli bacteria, from diverse habitats worldwide, increase their mutation rates in response to the stress of starvation.
4) The laboratory strains of E. coli, well loved by geneticists, are far more homogeneous than their relatives in nature. Previous studies of stationary-phase mutation processes in E. coli used descendants of a single laboratory strain (1). In the new work, Bjedov et al tested a collection of 787 E. coli isolates culled from diverse natural environments including air, water and sediments, and the guts of a variety of host organisms. To mimic the stress conditions encountered by bacteria in their natural environments, they subjected bacterial colonies that had formed during the exponential growth phase to starvation during a prolonged stationary growth phase. They then looked for the production of mutants in the starved aging colonies. The vast majority of old, stationary-phase colonies showed an increased number of mutants -- that is, they were stationary-phase mutators.
5) In a sample of colonies, the authors were able to link the increased mutagenesis to starvation and oxidative stress by showing that either additional sugar or anaerobic incubation could block the increased mutagenesis. These results demonstrate unambiguously that in the real world most bacteria undergo mutagenesis in response to starvation and the stationary phase of growth.
References (abridged):
1. S. M. Rosenberg, Nature Rev. Genet. 2, 504 (2001)
2. I. Bjedov et al., Science 300, 1404 (2003)
3. J. E. LeClerc et al. Science 274, 1208 (1996)
4. I. Matic et al., Science 277, 1833 (1997)
5. E. F. Mao et al., J. Bacteriol. 179, 417 (1997)
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