Diminishing returns from mutation supply rate in asexual populations

Science

Volumn 283, Issue 5400, 1999, Pages 404-406

  De Visser, J Arjan G M ^a,b   Zeyl, Clifford W ^c   Gerrish, Philip J ^d   Blanchard, Jeffrey L ^e   Lenski, Richard E ^b  

^a WAGENINGEN UNIVERSITY   (Netherlands)

^b MICHIGAN STATE UNIVERSITY   (United States)

^c WAKE FOREST UNIVERSITY   (United States)

^d CENTERS FOR DISEASE CONTROL AND PREVENTION   (United States)

^e UNIVERSITY OF OREGON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTATION; ARTICLE; ESCHERICHIA COLI; EVOLUTION; GENETIC LINKAGE; GENOTYPE; MUTATION RATE; NONHUMAN; POPULATION DENSITY; POPULATION GENETICS; PREDICTION; PRIORITY JOURNAL; STRAIN DIFFERENCE;

ADAPTATION, PHYSIOLOGICAL; ESCHERICHIA COLI; EVOLUTION; GENETICS, POPULATION; GENOTYPE; LINEAR MODELS; MODELS, BIOLOGICAL; MUTATION;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; NEGIBACTERIA; PROKARYOTA;

EID: 0033555421     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.283.5400.404     Document Type: Article

References (29)

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11. This model (6) makes certain simplifying assumptions. In particular, it ignores deleterious mutations and multiple beneficial mutations. The rate of adaptation may decelerate and even become negative at very high mutation rates, especially in asexual populations [A. S. Kondrashov, Genet. Res. 66, 53 (1995)]. Very high mutation rates might also produce genotypes with two or more beneficial mutations that could overcome clonal interference (although we might then expect interference to arise between genotypes that each carried multiple beneficial mutations). The former assumption depends on per capita mutation rate but not population size, whereas the latter assumption rests on both mutation rate and population size. By manipulating these two factors independently, we should be able to discern if violations of the assumptions are important over the wide range of values explored, which does not appear to be the case.
12. The populations were serially propagated at 37°C in test-tubes containing 10 ml of Davis minimal medium (DM) supplemented with glucose (25 μg/ml). Every 200 generations, samples were taken and stored at -80°C for later study.
13. +) is the progenitor of all strains used in this study. REL4548 was derived from REL606 after 10,000 generations in the glucose-limited environment, during which time its fitness increased by ∼50% relative to REL606 because of the substitution of several beneficial mutations [R. E. Lenski and M. Travisano, Proc. Natl. Acad. Sci. U.S.A. 91, 6808 (1994)]. REL4548 retained functional DNA repair, unlike some other lines in an earlier experiment (3). These strains had no plasmids or functional viruses, so populations were strictly asexual.
14. Repair-deficient alleles mutY::mini-Tn10 (strain NR9373 [J. P. Radicella, E. A. Clark, M. S. Fox, Proc. Natl. Acad. Sci. U.S.A. 85, 9674 (1988)]) and mutS::TnS (strain ES1301) [E. C. Siegel, S. L. Wain, S. F. Meltzer, M. L. Binion, J. L. Steinberg, Mut. Res. 93, 25 (1982)] were moved into each background by P1 transduction [J. W. Zyskind and S. I. Bernstein, Recombinant DNA Laboratory Manual (Academic Press, San Diego, CA, 1989)]. The mutY allele increases G:C to T:A transversions, whereas mutS increases G:C to A:T and A:T to G:C transitions as well as frame shifts [J. H. Miller, Annu. Rev. Microbiol. 50, 625 (1996)]. The mini-Tn10 insertion was inactive, but Tn5 (or its IS element, IS50) was active in some evolving mutS populations. However, there was no association between number of changes detected by Southern (DNA) blots, with IS50 as a probe, and final extent of fitness gains, on the basis of analysis of covariance (P = 0.333, data not shown).
15. Repair-deficient alleles mutY::mini-Tn10 (strain NR9373 [J. P. Radicella, E. A. Clark, M. S. Fox, Proc. Natl. Acad. Sci. U.S.A. 85, 9674 (1988)]) and mutS::TnS (strain ES1301) [E. C. Siegel, S. L. Wain, S. F. Meltzer, M. L. Binion, J. L. Steinberg, Mut. Res. 93, 25 (1982)] were moved into each background by P1 transduction [J. W. Zyskind and S. I. Bernstein, Recombinant DNA Laboratory Manual (Academic Press, San Diego, CA, 1989)]. The mutY allele increases G:C to T:A transversions, whereas mutS increases G:C to A:T and A:T to G:C transitions as well as frame shifts [J. H. Miller, Annu. Rev. Microbiol. 50, 625 (1996)]. The mini-Tn10 insertion was inactive, but Tn5 (or its IS element, IS50) was active in some evolving mutS populations. However, there was no association between number of changes detected by Southern (DNA) blots, with IS50 as a probe, and final extent of fitness gains, on the basis of analysis of covariance (P = 0.333, data not shown).
16. Repair-deficient alleles mutY::mini-Tn10 (strain NR9373 [J. P. Radicella, E. A. Clark, M. S. Fox, Proc. Natl. Acad. Sci. U.S.A. 85, 9674 (1988)]) and mutS::TnS (strain ES1301) [E. C. Siegel, S. L. Wain, S. F. Meltzer, M. L. Binion, J. L. Steinberg, Mut. Res. 93, 25 (1982)] were moved into each background by P1 transduction [J. W. Zyskind and S. I. Bernstein, Recombinant DNA Laboratory Manual (Academic Press, San Diego, CA, 1989)]. The mutY allele increases G:C to T:A transversions, whereas mutS increases G:C to A:T and A:T to G:C transitions as well as frame shifts [J. H. Miller, Annu. Rev. Microbiol. 50, 625 (1996)]. The mini-Tn10 insertion was inactive, but Tn5 (or its IS element, IS50) was active in some evolving mutS populations. However, there was no association between number of changes detected by Southern (DNA) blots, with IS50 as a probe, and final extent of fitness gains, on the basis of analysis of covariance (P = 0.333, data not shown).
17. Repair-deficient alleles mutY::mini-Tn10 (strain NR9373 [J. P. Radicella, E. A. Clark, M. S. Fox, Proc. Natl. Acad. Sci. U.S.A. 85, 9674 (1988)]) and mutS::TnS (strain ES1301) [E. C. Siegel, S. L. Wain, S. F. Meltzer, M. L. Binion, J. L. Steinberg, Mut. Res. 93, 25 (1982)] were moved into each background by P1 transduction [J. W. Zyskind and S. I. Bernstein, Recombinant DNA Laboratory Manual (Academic Press, San Diego, CA, 1989)]. The mutY allele increases G:C to T:A transversions, whereas mutS increases G:C to A:T and A:T to G:C transitions as well as frame shifts [J. H. Miller, Annu. Rev. Microbiol. 50, 625 (1996)]. The mini-Tn10 insertion was inactive, but Tn5 (or its IS element, IS50) was active in some evolving mutS populations. However, there was no association between number of changes detected by Southern (DNA) blots, with IS50 as a probe, and final extent of fitness gains, on the basis of analysis of covariance (P = 0.333, data not shown).
18. 5, respectively. The different dilution factors might influence the selective environment, as well as effective population size, because the treatments spend different periods in lag, growth, and stationary phases. This difference is unimportant if faster exponential growth is primarily responsible for fitness gains, as reported previously for this system [F. Vasi, M. Travisano, R. E. Lenski, Am. Nat. 144, 432 (1994)]. We tested the similarity of the selective environments by measuring the final fitness of all populations under both demographic regimes. There were significant positive correlations in fitness between the two regimes for population derived from nonadapted (r = 0.696, n = 24, one-tailed P < 0.0001) and adapted (r = 0.369, n = 24, one-tailed P = 0.03.79) founders, confirming that the two regimes present similar selective environments.
19. + and two were Ara ). Samples from the 24 populations founded by the nonadapted strain were assayed at 200, 400, 600, 800, and 1000 generations, with fourfold replication. Assays were performed for the 24 populations founded by the well-adapted strain only after 1000 generations, but with 10-fold replication. All fitness values were adjusted for the effect, if any, of the Ara marker on the basis of control experiments with isogenic strains differing only in their marker state.
20. Fluctuation tests [S. E. Luria and M. Delbrück, Genetics 28, 491 (1943)] were performed to estimate the mutation rate of founding strains, following protocols described elsewhere (3). Tests were replicated 24-fold for resistance to nalidixic-acid and 12-fold for resistances to T4, T5, and rifampicin. Maximum-likelihood estimates were calculated by a local program (3). As an overall measure of mutation rate, we used the geometric mean of eight (four loci tested X two Ara marker strains) estimates for each combination of mutator allele (wild type, mutY, or mutS) and initial fitness (nonadapted or adapted). Rates are expressed relative to wild type in Table 1.
21. 1,20 = 350.61, P < 0.0001).
22. Small populations should also fix mutations with smaller beneficial effects, on average, than those substituted in large populations (6, 21).
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26. In idealized sexual populations that lack any genetic linkage, the rate of adaptive evolution should be proportional to mutation supply rate over its entire range. In reality, sexual organisms have linkage that prevents completely free recombination and may produce some weaker form of a speed limit on adaptive evolution.
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29. We thank L. Ekunwe, N. Hajela, J. Mongold, and M. Stanek for technical assistance, and B. Bohannan, V. Cooper, A. Kondrashov, P. Moore, D. Rozen, P. Sniegowski, M. Stanek, and an anonymous referee for suggestions and discussion. This work was supported by a fellowship from the Netherlands Organization for Scientific Research to J.A.G.M.dV. and a grant from the NSF to R.E.L.