Evolvability is the ability of a biological system to produce phenotypic variation that is both heritable and adaptive. It has long been the subject of anecdotal observations and theoretical work. In recent years, however, the molecular causes of evolvability have been an increasing focus of experimental work. Here, we review recent experimental progress in areas as different as the evolution of drug resistance in cancer cells and the rewiring of transcriptional regulation circuits in vertebrates. This research reveals the importance of three major themes: multiple genetic and non-genetic mechanisms to generate phenotypic diversity, robustness in genetic systems, and adaptive landscape topography. We also discuss the mounting evidence that evolvability can evolve and the question of whether it evolves adaptively.
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The authors thank M. Ackermann, B. Bogos, S. A. Frank, J. Van Gestel, A. R. Hall, D. Kiviet and M. Toll Riera for discussions and the reviewers for their constructive criticism. The authors apologize to their colleagues whose important contributions to evolvability research could not be covered owing to space constraints. J.L.P. acknowledges support from Swiss National Science Foundation Grant PP00P3_170604. A.W. acknowledges support from the European Research Council Advanced Grant 739874, Swiss National Science Foundation Grant 31003A_1728887 and the University Priority Research Program in Evolutionary Biology at the University of Zurich. J.L.P. and A.W. are also affiliated with the Swiss Institute of Bioinformatics, and A.W. is also affiliated with the Santa Fe Institute.
Nature Reviews Genetics thanks G. Wagner, J. Zhang and the other anonymous reviewer(s) for their contribution to the peer review of this work.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Isogenic populations
Populations of individuals with the same genotype.
- Phenotypic plasticity
The ability of one genotype to produce more than one phenotype in response to different environmental stimuli.
The extent to which a system can be partitioned into distinct components.
When one gene or one mutation affects multiple phenotypes.
- Pre-mutation evolvability
Evolvability driven by new mutations.
- Post-mutation evolvability
Evolvability driven by existing genetic variation within a population — for example, via recombination acting on that variation.
- Gene expression noise
Variability among isogenic cells in transcript or protein abundance.
- Viral latency
The ability of a virus to remain dormant in a host cell.
The ability of a cell to take up DNA from the environment.
- Population bottleneck
A temporary, drastic reduction in population size.
- Genetic assimilation
A process by which a new phenotype that results from an environmental perturbation becomes genetically encoded.
- Kinetic trapping
Occurs when a protein does not reach its minimum free energy structure but rather becomes trapped in a non-equilibrium structure.
- Stop-codon readthrough
When translation does not terminate at a stop codon but rather continues to extend an amino acid chain.
Proteins that propagate by inducing properly folded proteins to convert into a misfolded form, often resulting in aggregation.
- Cryptic genetic variation
Genetic variation that normally causes little to no phenotypic variation but that has the potential to cause phenotypic variation in new environments or new genetic backgrounds.
A short DNA sequence that is bound by regulatory proteins to activate the transcription of a gene, which may be located many thousands of base pairs away.
Proteins that assist other proteins in folding or that refold misfolded proteins.
- Epistatic interactions
Non-additive interactions between alleles in their contribution to a phenotype or fitness.
- Protein domain
A distinct functional and often autonomously folding unit of a protein.
- Genotype space
The space of all possible genotypes. For a nucleic acid sequence of length L, this space comprises 4L genotypes.
A real-valued function on an interval of real numbers is concave if any line connecting two points on the graph of the function lies on or below the graph.
A real-valued function on an interval of real numbers is convex if any line connecting two points on the graph of the function lies above or on the graph.
- Adaptive walks
A series of mutations that never decrease fitness.
- Saddle points
Points on a landscape that have zero slope in at least two orthogonal directions yet are not local peaks.
- Extradimensional bypasses
Accessible mutational paths to an adaptive peak that are facilitated by increasing the dimensionality of an adaptive landscape.
- Quantitative trait loci
Loci that explain part of the genetic basis of variation in a phenotype.
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Payne, J.L., Wagner, A. The causes of evolvability and their evolution. Nat Rev Genet 20, 24–38 (2019). https://doi.org/10.1038/s41576-018-0069-z
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