Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 7 April 2006:
Vol. 312. no. 5770, pp. 111 - 114
DOI: 10.1126/science.1123539
Prev | Table of Contents | Next

Reports

Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins

Daniel M. Weinreich,* Nigel F. Delaney,{dagger} Mark A. DePristo, Daniel L. Hartl

Five point mutations in a particular ß-lactamase allele jointly increase bacterial resistance to a clinically important antibiotic by a factor of ~100,000. In principle, evolution to this high-resistance ß-lactamase might follow any of the 120 mutational trajectories linking these alleles. However, we demonstrate that 102 trajectories are inaccessible to Darwinian selection and that many of the remaining trajectories have negligible probabilities of realization, because four of these five mutations fail to increase drug resistance in some combinations. Pervasive biophysical pleiotropy within the ß-lactamase seems to be responsible, and because such pleiotropy appears to be a general property of missense mutations, we conclude that much protein evolution will be similarly constrained. This implies that the protein tape of life may be largely reproducible and even predictable.

Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.

{dagger} Present address: Integrative Oceanography Division, Scripps Institute of Oceanography, 9500 Gilman Drive, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: dmw{at}post.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Population Genetics of Adaptation: Multiple Substitutions on a Smooth Fitness Landscape.
R. L. Unckless and H. A. Orr (2009)
Genetics 183, 1079-1086
   Abstract »    Full Text »    PDF »
Temporal Constraints on the Incorporation of Regulatory Mutants in Evolutionary Pathways.
K. M. Brown, M. A. DePristo, D. M. Weinreich, and D. L. Hartl (2009)
Mol. Biol. Evol. 26, 2455-2462
   Abstract »    Full Text »    PDF »
Predicting Virus Evolution: The Relationship between Genetic Robustness and Evolvability of Thermotolerance.
C.B. Ogbunugafor, R.C. Mcbride, and P.E. Turner (2009)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Markov models for accumulating mutations.
N. Beerenwinkel and S. Sullivant (2009)
Biometrika 96, 645-661
   Abstract »    PDF »
Climbing Mount Probable: Mutation as a Cause of Nonrandomness in Evolution.
A. Stoltzfus and L. Y. Yampolsky (2009)
J. Hered. 100, 637-647
   Abstract »    Full Text »    PDF »
Evolutionary Insights on C4 Photosynthetic Subtypes in Grasses from Genomics and Phylogenetics.
P.-A. Christin, E. Samaritani, B. Petitpierre, N. Salamin, and G. Besnard (2009)
Gen Biol Evol 2009, 221-230
   Abstract »    Full Text »    PDF »
The evolutionary origins of beneficial alleles during the repeated adaptation of garter snakes to deadly prey.
C. R. Feldman, E. D. Brodie Jr, E. D. Brodie III, and M. E. Pfrender (2009)
PNAS 106, 13415-13420
   Abstract »    Full Text »    PDF »
Mutational paths towards increased fluoroquinolone resistance in Legionella pneumophila.
I. Almahmoud, E. Kay, D. Schneider, and M. Maurin (2009)
J. Antimicrob. Chemother. 64, 284-293
   Abstract »    Full Text »    PDF »
Phylogenomics of C4 Photosynthesis in Sedges (Cyperaceae): Multiple Appearances and Genetic Convergence.
G. Besnard, A. M. Muasya, F. Russier, E. H. Roalson, N. Salamin, and P.-A. Christin (2009)
Mol. Biol. Evol. 26, 1909-1919
   Abstract »    Full Text »    PDF »
Stepwise acquisition of pyrimethamine resistance in the malaria parasite.
E. R. Lozovsky, T. Chookajorn, K. M. Brown, M. Imwong, P. J. Shaw, S. Kamchonwongpaisan, D. E. Neafsey, D. M. Weinreich, and D. L. Hartl (2009)
PNAS 106, 12025-12030
   Abstract »    Full Text »    PDF »
Colloquium Papers: In the light of directed evolution: Pathways of adaptive protein evolution.
J. D. Bloom and F. H. Arnold (2009)
PNAS 106, 9995-10000
   Abstract »    Full Text »    PDF »
Experimental evolution of a microbial predator's ability to find prey.
K. L Hillesland, G. J Velicer, and R. E Lenski (2009)
Proc R Soc B 276, 459-467
   Abstract »    Full Text »    PDF »
Evolution of C4 Phosphoenolpyruvate Carboxykinase in Grasses, from Genotype to Phenotype.
P.-A. Christin, B. Petitpierre, N. Salamin, L. Buchi, and G. Besnard (2009)
Mol. Biol. Evol. 26, 357-365
   Abstract »    Full Text »    PDF »
Adaptive protein evolution grants organismal fitness by improving catalysis and flexibility.
P. E. Tomatis, S. M. Fabiane, F. Simona, P. Carloni, B. J. Sutton, and A. J. Vila (2008)
PNAS 105, 20605-20610
   Abstract »    Full Text »    PDF »
Ohno's Model Revisited: Measuring the Frequency of Potentially Adaptive Mutations under Various Mutational Drifts.
S. Bershtein and D. S. Tawfik (2008)
Mol. Biol. Evol. 25, 2311-2318
   Abstract »    Full Text »    PDF »
Evolutionary Switch and Genetic Convergence on rbcL following the Evolution of C4 Photosynthesis.
P.-A. Christin, N. Salamin, A. M. Muasya, E. H. Roalson, F. Russier, and G. Besnard (2008)
Mol. Biol. Evol. 25, 2361-2368
   Abstract »    Full Text »    PDF »
Accelerated evolution of resistance in multidrug environments.
M. Hegreness, N. Shoresh, D. Damian, D. Hartl, and R. Kishony (2008)
PNAS 105, 13977-13981
   Abstract »    Full Text »    PDF »
Energy-dependent fitness: A quantitative model for the evolution of yeast transcription factor binding sites.
V. Mustonen, J. Kinney, C. G. Callan Jr, and M. Lassig (2008)
PNAS 105, 12376-12381
   Abstract »    Full Text »    PDF »
Inaugural Article: Historical contingency and the evolution of a key innovation in an experimental population of Escherichia coli.
Z. D. Blount, C. Z. Borland, and R. E. Lenski (2008)
PNAS 105, 7899-7906
   Abstract »    Full Text »    PDF »
The Frequency of Fitness Peak Shifts Is Increased at Expanding Range Margins Due to Mutation Surfing.
O. J. Burton and J. M. J. Travis (2008)
Genetics 179, 941-950
   Abstract »    Full Text »    PDF »
The genetic basis of parallel and divergent phenotypic responses in evolving populations of Escherichia coli.
E. A Ostrowski, R. J Woods, and R. E Lenski (2008)
Proc R Soc B 275, 277-284
   Abstract »    Full Text »    PDF »
A burst of protein sequence evolution and a prolonged period of asymmetric evolution follow gene duplication in yeast.
D. R. Scannell and K. H. Wolfe (2008)
Genome Res. 18, 137-147
   Abstract »    Full Text »    PDF »
Crystal Structure of an Ancient Protein: Evolution by Conformational Epistasis.
E. A. Ortlund, J. T. Bridgham, M. R. Redinbo, and J. W. Thornton (2007)
Science 317, 1544-1548
   Abstract »    Full Text »    PDF »
Mutational Reversions During Adaptive Protein Evolution.
M. A. DePristo, D. L. Hartl, and D. M. Weinreich (2007)
Mol. Biol. Evol. 24, 1608-1610
   Abstract »    Full Text »    PDF »
Profile of Daniel L. Hartl.
H. D. Tinsley (2007)
PNAS 104, 9111-9113
   Full Text »    PDF »
Evolvability of physiological and biochemical traits: evolutionary mechanisms including and beyond single-nucleotide mutation.
M. E. Feder (2007)
J. Exp. Biol. 210, 1653-1660
   Abstract »    Full Text »    PDF »
Adaptive Divergence in Experimental Populations of Pseudomonas fluorescens. III. Mutational Origins of Wrinkly Spreader Diversity.
E. Bantinaki, R. Kassen, C. G. Knight, Z. Robinson, A. J. Spiers, and P. B. Rainey (2007)
Genetics 176, 441-453
   Abstract »    Full Text »    PDF »
Fitness Landscape of Human Immunodeficiency Virus Type 1 Protease Quasispecies.
G. Fernandez, B. Clotet, and M. A. Martinez (2007)
J. Virol. 81, 2485-2496
   Abstract »    Full Text »    PDF »
Deterministic and Stochastic Regimes of Asexual Evolution on Rugged Fitness Landscapes.
K. Jain and J. Krug (2007)
Genetics 175, 1275-1288
   Abstract »    Full Text »    PDF »
Adaptations to fluctuating selection in Drosophila.
V. Mustonen and M. Lassig (2007)
PNAS 104, 2277-2282
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)