The Selective Cause of an Ancient Adaptation

Zhu, Guoping; Golding, G. Brian; Dean, Anthony M.

doi:10.1126/science.1106974

Cited by 129 publications

(162 citation statements)

References 26 publications

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“…For several cases, however, ancestral molecules have been engineered, allowing studies of functional changes in the past (6). These analyses demonstrate that functional changes actually occurred, but they do not necessarily mean that the new characters were adaptive (7). To complicate the matter further, evolutionary changes are not always unidirectional and ancestral phenotypes may reappear during evolution (8,9).…”

mentioning

confidence: 99%

Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebrates

Yokoyama

Tada

Zhang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

234

292

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Vertebrate ancestors appeared in a uniform, shallow water environment, but modern species flourish in highly variable niches. A striking array of phenotypes exhibited by contemporary animals is assumed to have evolved by accumulating a series of selectively advantageous mutations. However, the experimental test of such adaptive events at the molecular level is remarkably difficult. One testable phenotype, dim-light vision, is mediated by rhodopsins. Here, we engineered 11 ancestral rhodopsins and show that those in early ancestors absorbed light maximally ( max) at 500 nm, from which contemporary rhodopsins with variable maxs of 480 -525 nm evolved on at least 18 separate occasions. These highly environment-specific adaptations seem to have occurred largely by amino acid replacements at 12 sites, and most of those at the remaining 191 (Ϸ94%) sites have undergone neutral evolution. The comparison between these results and those inferred by commonly-used parsimony and Bayesian methods demonstrates that statistical tests of positive selection can be misleading without experimental support and that the molecular basis of spectral tuning in rhodopsins should be elucidated by mutagenesis analyses using ancestral pigments. molecular adaptation ͉ rhodopsin

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mentioning

confidence: 99%

Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebrates

Yokoyama

Tada

Zhang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

234

292

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“…Only recent efforts have aimed at identifying changes in sequence and structure that affect fitness within a defined protein fold (4, 7, 8, 10, 11). The identification of such structural traits acquired through evolution allows both the reconstruction of ancestral genes (7,8,12) and the prediction of future evolutionary events (5,13). The latter approach could be immensely valuable for anticipating the molecular features that might enhance bacterial resistance to antibiotics, thereby informing strategies to combat this clinical threat.…”

mentioning

confidence: 99%

“…P rotein evolution is crucial for organismal adaptation and fitness (1)(2)(3)(4)(5)(6)(7)(8). This process takes place by shaping a given 3-dimensional fold for its particular biochemical function within the metabolic requirements and constraints of the environment.…”

mentioning

confidence: 99%

Adaptive protein evolution grants organismal fitness by improving catalysis and flexibility

Tomatis

Fabiane

Simona

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

101

102

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Protein evolution is crucial for organismal adaptation and fitness. This process takes place by shaping a given 3-dimensional fold for its particular biochemical function within the metabolic requirements and constraints of the environment. The complex interplay between sequence, structure, functionality, and stability that gives rise to a particular phenotype has limited the identification of traits acquired through evolution. This is further complicated by the fact that mutations are pleiotropic, and interactions between mutations are not always understood. Antibiotic resistance mediated by ␤-lactamases represents an evolutionary paradigm in which organismal fitness depends on the catalytic efficiency of a single enzyme. Based on this, we have dissected the structural and mechanistic features acquired by an optimized metallo-␤-lactamase (M␤L) obtained by directed evolution. We show that antibiotic resistance mediated by this enzyme is driven by 2 mutations with sign epistasis. One mutation stabilizes a catalytically relevant intermediate by fine tuning the position of 1 metal ion; whereas the other acts by augmenting the protein flexibility. We found that enzyme evolution (and the associated antibiotic resistance) occurred at the expense of the protein stability, revealing that M␤Ls have not exhausted their stability threshold. Our results demonstrate that flexibility is an essential trait that can be acquired during evolution on stable protein scaffolds. Directed evolution aided by a thorough characterization of the selected proteins can be successfully used to predict future evolutionary events and design inhibitors with an evolutionary perspective.antibiotic resistance ͉ enzyme ͉ fitness landscape ͉ metalloproteins ͉ epistasis P rotein evolution is crucial for organismal adaptation and fitness (1-8). This process takes place by shaping a given 3-dimensional fold for its particular biochemical function within the metabolic requirements and constraints of the environment.

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“…However, no conclusive experimental evidence has been provided to support this theory up to now. Site-directed mutagenesis experiments have shown that the coenzyme specificity of MDH is determined by a limited number of amino acid residues (Tomita et al, 2005(Tomita et al, , 2006b, and that the coenzyme specificity of some dehydrogenases could be shifted by alteration of a few specific amino acids in the enzyme to adapt to the environment during the enzyme's evolution (Zhu et al, 2005). In the present study, we altered the coenzyme specificity of MDH from a Gram-positive bacterium S. coelicolor A3(2).…”

Section: Discussionmentioning

confidence: 99%

Alteration of coenzyme specificity of malate dehydrogenase from Streptomyces coelicolor A3(2) by site-directed mutagenesis

Song

Cao

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We describe here for the first time the alteration of coenzyme specificity of malate dehydrogenase (MDH) from Streptomyces coelicolor A3(2) (ScMDH). In the present study, we replaced four amino acid residues in the Rossmann fold (βB-αC) region of NADH-dependent ScMDH by site-directed mutagenesis with those of NADPH-dependent MDH (Glu42Gly, Ile43Ser, Pro45Arg, and Ala46Ser). The coenzyme specificity of the mutant enzyme (ScMDH-T4) was examined. Coenzyme specificity of ScMDH-T4 was shifted 2231.3-fold toward NADPH using k cat /K m coenzyme as the measurement of coenzyme specificity. Accordingly, the effect of the replacements on coenzyme specificity is discussed. Our work provides further insight into the coenzyme specificity of ScMDH.

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The Selective Cause of an Ancient Adaptation

Cited by 129 publications

References 26 publications

Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebrates

Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebrates

Adaptive protein evolution grants organismal fitness by improving catalysis and flexibility

Alteration of coenzyme specificity of malate dehydrogenase from Streptomyces coelicolor A3(2) by site-directed mutagenesis

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