Proteins display generic properties that are challenging to explain by direct selection, notably allostery, the capacity to be regulated through long-range effects, and evolvability, the capacity to adapt to new selective pressures. An evolutionary scenario is proposed where proteins acquire these two features indirectly as a by-product of their selection for a more fundamental property, exquisite discrimination, the capacity to bind discriminatively very similar ligands. Achieving this task  typically require proteins to undergo a conformational change. We argue that physical and evolutionary constraints impel this change to be controlled by a group of sites extending from the binding site. Proteins may thus acquire a latent potential for allosteric regulation and evolutionary adaptation  . This scenario accounts for the groups of conserved and coevolving residues observed in multiple sequence alignments. However, we propose that most pairs of coevolving and contacting residues inferred from such alignments have a different origin, related to thermal stability. An elementary physical model is presented that illustrates this evolutionary scenario and its implications. Based on minimal assumptions, the model recapitulates and links several well-known features of proteins and makes new predictions amenable to experimental tests .
Proteins display generic properties that are challenging to explain by direct selection, notably allostery, the capacity to be regulated through long-range effects, and evolvability, the capacity to adapt to new selective pressures. An evolutionary scenario is proposed where proteins acquire these two features indirectly as a by-product of their selection for a more fundamental property, exquisite discrimination, the capacity to bind discriminatively very similar ligands. Achieving this task is shown to typically require proteins to undergo a conformational change. We argue that physical and evolutionary constraints impel this change to be controlled by a group of sites extending from the binding site. Proteins can thus acquire a latent potential for allosteric regulation and evolutionary adaptation because of long-range effects that initially arise as evolutionary spandrels . This scenario accounts for the groups of conserved and coevolving residues observed in multiple sequence alignments. However, we propose that most pairs of coevolving and contacting residues inferred from such alignments have a different origin, related to thermal stability. A physical model is presented that illustrates this evolutionary scenario and its implications. The scenario can be implemented in experiments of protein evolution to directly test its predictions .
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is shown to
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may
can
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because of long-range effects that initially arise as evolutionary spandrels
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An elementary
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Based on minimal assumptions, the model recapitulates and links several well-known features of proteins and makes new predictions amenable to experimental tests
The scenario can be implemented in experiments of protein evolution to directly test its predictions