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  • Review Article
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Between genotype and phenotype: protein chaperones and evolvability

Key Points

  • The evolution of evolvability as an adaptive property of populations necessitates the consideration of group or lineage selection.

  • Previous mechanisms of evolvability dealt with regulation of the mutation rate; this review focuses on the regulation of the 'expressed mutation rate'.

  • Protein folding in vivo is facilitated by molecular chaperones.

  • Protein-folding chaperones buffer coding mutations directly by allowing mutant polypeptides to fold into functional structures.

  • Although, in the wild, Drosophila experience potentially lethal temperatures, they are protected from protein damage, lethality and morphological abnormalities by Hsp70.

  • Hsp90 regulates developmental pathways and the expression of pronounced morphological variation for threshold traits in Drosophila.

  • The potential evolutionary consequences of protein-folding capacitors are distinct from those of signal-transduction capacitors.

  • Stress-sensitive regulation of HSP90 buffering provides a plausible way to remodel normally robust developmental networks.

Abstract

Protein chaperones direct the folding of polypeptides into functional proteins, facilitate developmental signalling and, as heat-shock proteins (HSPs), can be indispensable for survival in unpredictable environments. Recent work shows that the main HSP chaperone families also buffer phenotypic variation. Chaperones can do this either directly through masking the phenotypic effects of mutant polypeptides by allowing their correct folding, or indirectly through buffering the expression of morphogenic variation in threshold traits by regulating signal transduction. Environmentally sensitive chaperone functions in protein folding and signal transduction have different potential consequences for the evolution of populations and lineages under selection in changing environments.

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Figure 1: Hierarchical constraints on evolvability.
Figure 2: Group fitness and evolutionary capacitors.
Figure 3: HSP90 targets in a signalling network.

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Acknowledgements

We thank S. Henikoff, S. Rosenberg, W. Fontana and three anonymous reviewers for their insightful comments.

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DATABASES

LocusLink

sevenless

Saccharomyces Genome Database

RAD30

FURTHER INFORMATION

Science STKE

Glossary

CHAPERONES

A class of proteins that, by preventing improper associations, assist in the correct folding or assembly of other proteins in vivo, but that are not a part of the mature structure.

EVOLVABILITY

The ability of random genetic variation to produce phenotypic changes that can increase fitness (intrinsic evolvability) or the ability of a population to respond to selection (extrinsic evolvability). Extrinsic evolvability depends on intrinsic evolvability, as well as on external variables such as the history, size and structure of the population.

GROUP SELECTION

Selection on traits that increase the relative fitness of populations or lineages of organisms at some fitness cost to individuals. All of the feasible mechanisms require selection on lineages or small interbreeding groups of related individuals in subdivided populations.

MUTATION LOAD

The accumulated deleterious alleles that are carried by a population at any given time.

EXPRESSED MUTATION RATE

The rate of phenotypic change that results from the continuing accumulation of new mutations (expressed mutation rate = total mutation rate − neutral mutation rate).

THRESHOLD TRAITS

Quantitative traits that are discretely expressed in a limited number of phenotypes (usually two), but which are based on an assumed continuous distribution of factors that contribute to the trait (underlying liability).

GENETIC DRIFT

The stochastic change in gene frequency that results from binomial sampling of alleles segregating in finite populations.

ENDOSYMBIOTIC BACTERIA

Non-pathogenic bacteria that live inside host cells.

PURIFYING SELECTION

Selection against deleterious alleles that arise in a population, preventing their increase in frequency and assuring their eventual disappearance from the gene pool.

PHENOCOPY

The production of a phenotype as a result of environmental factors, such as stress, which closely resembles a phenotype that normally results from specific gene expression or from gene mutation.

ADAPTIVE RADIATION

The expansion of a lineage into a group of new lineages by speciation. It is often associated with the exploitation of new ecological niches.

CLADE

A group of species that has diversified from a common ancestor.

EFFECTIVE POPULATION SIZE

(Ne). The theoretical size of an idealized population for which the genetic variation in a sample is explained solely by mutation and genetic drift.

HERITABILITY

The proportion of total phenotypic variation that can be attributed to genetic effects (broad sense) or purely additive genetic effects (narrow sense). Narrow-sense heritability predicts the initial response of a population to selection and decreases over the course of selection.

STABILIZING SELECTION

Selection for an intermediate phenotypic optimum that is fitter than either higher or lower phenotypes.

SPANDRELS

Features that arise as an unselected byproduct of selectively adaptive features, which are therefore easily co-opted to a new function.

EXAPTATIONS

Features (such as feathers) that evolved by selection for one purpose (such as warmth) and were later adapted to a new purpose (such as flight).

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Rutherford, S. Between genotype and phenotype: protein chaperones and evolvability. Nat Rev Genet 4, 263–274 (2003). https://doi.org/10.1038/nrg1041

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