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Neutralism and selectionism are extremes of an explanatory spectrum for understanding patterns of molecular evolution and the emergence of evolutionary innovation. Although recent genome-scale data from protein-coding genes argue against neutralism, molecular engineering and protein evolution data argue that neutral mutations and mutational robustness are important for evolutionary innovation. Here I propose a reconciliation in which neutral mutations prepare the ground for later evolutionary adaptation. Key to this perspective is an explicit understanding of molecular phenotypes that has only become accessible in recent years.
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