Darwinian evolution can follow only very few mutational paths to fitter proteins

被引:989
作者
Weinreich, DM [1 ]
Delaney, NF [1 ]
DePristo, MA [1 ]
Hartl, DL [1 ]
机构
[1] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA
关键词
D O I
10.1126/science.1123539
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Five point mutations in a particular beta-lactamase allele jointly increase bacterial resistance to a clinically important antibiotic by a factor of similar to 100,000. In principle, evolution to this high-resistance beta-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 beta-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.
引用
收藏
页码:111 / 114
页数:4
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