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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I am grateful to M. Isalan for pointing me to the role of zinc fingers in protein engineering. I would also like to thank S. Guindon for assistance with his software, fitModeL. This work was in part supported by grant 315200-116814 from the Swiss National Science Foundation.
- Effective population size
Indicates how many individuals actually contribute alleles to the next generation, as opposed to the actual number of individuals in a population. For various reasons, including the preferential reproduction of some individuals and population size fluctuations over time, the effective population size is typically smaller than the actual number of individuals in the population.
For a matrix A and a vector v, an eigenvalue c is a scalar that obeys the equation Av = cv.
The dependency of the effects of a mutation on mutations in other parts of a gene or genome.
- Gene ontology
A widely used classification system of gene functions and other gene attributes that uses a controlled vocabulary.
- Maximum-likelihood estimation
A statistical method for fitting mathematical models to data. It is widely used to estimate the structure of phylogenetic trees from sequence data.
- McDonald–Kreitman test
A statistical test that can detect positive selection based on intra- and interpopulation divergence of nucleotide changes in proteins.
- Molecular phenotype
A phenotype is any observable trait or feature of an organism other than the DNA itself (that is, the genotype). Molecular features, such as the structure of a particular proteins, are molecular phenotypes.
- Mutational walk
A series of small mutational changes in sequence space.
- Positive selection
Also known as directional selection. A process by which natural selection favours a single beneficial genotype over other genotypes and may drive this genotype to a high frequency in a population.
- Selection coefficient
The fitness difference of a genotype compared with the wild-type genotype.
- Selective sweep
When a mutation with beneficial fitness effects arises in a population, natural selection may drive or sweep this mutation to a high frequency or to fixation (a frequency of 100%) within a short amount of time.
- Sequence space
All DNA, RNA or amino-acid sequences of a given length, that is, a given number of monomers.
- Zinc-finger domain
A protein domain in which a zinc ion is bound to two conserved cysteine and histidine residues, an interaction that stabilizes the structure of the domain.
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Wagner, A. Neutralism and selectionism: a network-based reconciliation. Nat Rev Genet 9, 965–974 (2008). https://doi.org/10.1038/nrg2473
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