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Evolutionary capacitance is the storage and release of variation, just as electric capacitors store and release charge. Living systems are robust to mutations. This means that living systems accumulate
genetic variation Genetic variation is the difference in DNA among individuals or the differences between populations among the same species. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources ...
without the variation having a
phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
effect. But when the system is disturbed (perhaps by stress), robustness breaks down, and the variation has phenotypic effects and is subject to the full force of
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
. An evolutionary capacitor is a molecular switch mechanism that can "toggle" genetic variation between hidden and revealed states. If some subset of newly revealed variation is adaptive, it becomes fixed by
genetic assimilation Genetic assimilation is a process described by Conrad H. Waddington by which a phenotype originally produced in response to an environmental condition, such as exposure to a teratogen, later becomes genetically encoded via artificial selection ...
. After that, the rest of variation, most of which is presumably deleterious, can be switched off, leaving the population with a newly evolved advantageous trait, but no long-term handicap. For evolutionary capacitance to increase
evolvability Evolvability is defined as the capacity of a system for adaptive evolution. Evolvability is the ability of a population of organisms to not merely generate genetic diversity, but to generate '' adaptive'' genetic diversity, and thereby evolve thr ...
in this way, the switching rate should not be faster than the timescale of genetic assimilation. This mechanism would allow for rapid
adaptation In biology, adaptation has three related meanings. Firstly, it is the dynamic evolutionary process of natural selection that fits organisms to their environment, enhancing their evolutionary fitness. Secondly, it is a state reached by the p ...
to new environmental conditions. Switching rates may be a function of stress, making genetic variation more likely to affect the phenotype at times when it is most likely to be useful for adaptation. In addition, strongly deleterious variation may be purged while in a partially cryptic state, so cryptic variation that remains is more likely to be adaptive than random mutations are. Capacitance can help cross "valleys" in the
fitness landscape Fitness may refer to: * Physical fitness, a state of health and well-being of the body * Fitness culture, a sociocultural phenomenon surrounding exercise and physical fitness * Fitness (biology), an individual's ability to propagate its genes * ...
, where a combination of two mutations would be beneficial, even though each is deleterious on its own. There is currently no consensus about the extent to which capacitance might contribute to evolution in natural populations. The possibility of evolutionary capacitance is considered to be part of the
extended evolutionary synthesis The Extended Evolutionary Synthesis (EES) consists of a set of theoretical concepts argued to be more comprehensive than the earlier modern synthesis of evolutionary biology that took place between 1918 and 1942. The extended evolutionary synthe ...
. Switches that turn robustness to phenotypic rather than genetic variation on and off do not fit the capacitance analogy, as their presence does not cause variation to accumulate over time. They have instead been called phenotypic stabilizers.


Enzyme promiscuity

In addition to their native reaction, many
enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
perform side reactions. Similarly, binding proteins may spend some proportion of their time bound to off-target proteins. These reactions or interactions may be of no consequence to current fitness but under altered conditions, may provide the starting point for adaptive evolution. For example, several mutations in the antibiotic resistance gene B-lactamase introduce
cefotaxime Cefotaxime is an antibiotic used to treat several bacterial infections in humans, other animals, and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urin ...
resistance but do not affect
ampicillin Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat several bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, s ...
resistance. In populations exposed only to ampicillin, such mutations may be present in a minority of members since there is not fitness cost (i.e. are within the neutral network). This represents cryptic genetic variation since if the population is newly exposed to cefotaxime, the minority members will exhibit some resistance.


Chaperones

Chaperones assist in
protein folding Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...
. The need to fold proteins correctly is a big restriction on the evolution of protein sequences. It has been proposed that the presence of chaperones may, by providing additional robustness to errors in folding, allow the exploration of a larger set of genotypes. When chaperones are overworked at times of environmental stress, this may "switch on" previously cryptic genetic variation.


Hsp90

The hypothesis that chaperones can act as evolutionary capacitors is closely associated with the heat shock protein
Hsp90 Hsp90 (heat shock protein 90) is a chaperone (protein), chaperone protein that assists other proteins to protein folding, fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of ...
. When Hsp90 is downregulated in the fruit fly ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
'', a broad range of different phenotypes are seen, where the identity of the phenotype depends on the genetic background. Also, a recent study on the model insect, the red flour beetle
Tribolium castaneum The red flour beetle (''Tribolium castaneum'') is a species of beetle in the family darkling beetle, Tenebrionidae, the darkling beetles. The red flour beetle, and other closely related beetles like ''Gnatocerus cornutus'', are a worldwide pest ( ...
, showed that Hsp90 impairment revealed a new phenotype, reduced-eye phenotype, which was stably inherited without further HSP90 inhibition (https://doi.org/10.1101/690727). This was thought to prove that the new phenotypes depended on pre-existing cryptic genetic variation that had merely been revealed. More recent evidence suggests that these data might be explained by new mutations caused by the reactivation of formally dormant transposable elements. However, this finding regarding transposable elements may be dependent on the strong nature of the Hsp90 knockdown used in that experiment.


GroEL

The overproduction of
GroEL GroEL is a protein which belongs to the chaperonin family of Chaperone (protein), molecular chaperones, and is found in many bacteria. It is required for the proper protein folding, folding of many proteins. To function properly, GroEL requires ...
in ''
Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'' increases
mutational robustness In evolutionary biology, robustness of a biological system (also called biological or genetic robustness) is the persistence of a certain characteristic or trait in a system under perturbations or conditions of uncertainty. Robustness in developm ...
. This can increase
evolvability Evolvability is defined as the capacity of a system for adaptive evolution. Evolvability is the ability of a population of organisms to not merely generate genetic diversity, but to generate '' adaptive'' genetic diversity, and thereby evolve thr ...
.


Yeast prion SI+/h1>

Sup35p is a
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
protein involved in recognising
stop codon In molecular biology, a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in messenger RNA correspond to the additio ...
s and causing
translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...
to stop correctly at the ends of proteins. Sup35p comes in a normal form ( si- and a
prion A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), w ...
form ( SI+. When SI+is present, this depletes the amount of normal Sup35p available. As a result, the rate of errors in which translation continues beyond a stop codon increases from about 0.3% to about 1%. This can lead to different growth rates, and sometimes different morphologies, in matched SI+and si-strains in a variety of stressful environments. Sometimes the SI+strain grows faster, sometimes si- this depends on the genetic background of the strain, suggesting that SI+taps into pre-existing cryptic genetic variation. Mathematical models suggest that SI+may have evolved, as an evolutionary capacitor, to promote
evolvability Evolvability is defined as the capacity of a system for adaptive evolution. Evolvability is the ability of a population of organisms to not merely generate genetic diversity, but to generate '' adaptive'' genetic diversity, and thereby evolve thr ...
. SI+appears more frequently in response to environmental stress. In yeast, more stop codon disappearances are in-frame, mimicking the effects of SI+ than would be expected from mutation bias or than are observed in other taxa that do not form the SI+prion. These observations are compatible with SI+acting as an evolutionary capacitor in the wild. Similar transient increases in error rates can evolve emergently in the absence of a "widget" like SI+ The primary advantage of a SI+like widget is to facilitate the subsequent evolution of lower error rates once genetic assimilation has occurred.


Gene knockouts

Gene knockout Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the gene targeting, targeted removal or inactivation of a specific gene within an organism's genome. This can be done t ...
s can be used to identify novel
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s or genomic regions which function as evolutionary capacitors. When a gene is knocked out, and its removal reveals phenotypic variation that was not previously observable, that gene is functioning as a phenotypic capacitor. If any of the variation is adaptive, it is functioning as an evolutionary capacitor.


Fruit Flies

Deficiency in at least 15 different genes reveals cryptic variation in wing morphology in
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
. While some of the variation revealed by these knockouts is deleterious, other variation has a relatively minor effect on
aerodynamics Aerodynamics () is the study of the motion of atmosphere of Earth, air, particularly when affected by a solid object, such as an airplane wing. It involves topics covered in the field of fluid dynamics and its subfield of gas dynamics, and is an ...
, and could even improve the flight capability of an individual.


Yeast

In
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
, the knockout of certain
chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...
regulating genes increases the differences in expression between yeast species. The majority of the variation in protein expression is attributable to
trans Trans- is a Latin prefix meaning "across", "beyond", or "on the other side of". Used alone, trans may refer to: Sociology * Trans, a sociological term which may refer to: ** Transgender, people who identify themselves with a gender that di ...
effects, suggesting that trans-regulatory processes are strongly involved in canalization. Unlike the chromatin regulators, the removal of genes which code for metabolic enzymes does not have a consistent effect on the difference in expression between species, with different enzyme knockouts either increasing, decreasing, or not significantly affecting the expression difference. Broader knockout samples in yeast have identified at least 300 genes which, when absent, increase morphological variation between yeast individuals. These capacitor genes predominantly occupy a few key domains in
gene ontology The Gene Ontology (GO) is a major bioinformatics initiative to unify the representation of gene and gene product attributes across all species. More specifically, the project aims to: 1) maintain and develop its controlled vocabulary of gene and ...
, including chromosome organization and DNA integrity, RNA elongation, protein modification,
cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
, and response to stimuli such as stress. More generally, capacitor genes are likely to express proteins which act as network hubs in the
interactome In molecular biology, an interactome is the whole set of molecular interactions in a particular cell. The term specifically refers to physical interactions among molecules (such as those among proteins, also known as protein–protein interactions ...
of a cell, and in the network of synthetic-lethal interactions. The confidence that a specific gene acts as a phenotypic capacitor is correlated with the number of protein-protein interactions observed for its expressed protein. However, proteins with the highest amount of interactions have reduced phenotypic capacitance, possibly due to increased duplication of regions coding these proteins in the genome, reducing the effect of a single knockout. Capacitor genes are less likely to have
paralog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...
s elsewhere in the genome; most capacitors identified in yeast are either singleton genes, or have historical paralogs from which they have diverged substantially in terms of expression. Singleton and duplicate capacitors largely exhibit disjoint behavior in the interactome. Singleton capacitors are most often part of highly interconnected complexes (such as the mediator complex), while duplicate capacitors are more highly connected and tend to interact with multiple large complexes. The gene ontologies of singleton and duplicate capacitors also differ notably. Singleton capacitors are concentrated in the categories of DNA maintenance and organization, response to stimuli, and RNA transcription and localization, whereas duplicate capacitors are concentrated in the categories of
protein metabolism Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism. The steps of protein synthesis include transcription, translation, an ...
and
endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...
.


Redundancy

The mechanism of phenotypic capacitor genes in yeast appears to be closely related to the modalities of functional redundancy at various levels of the genome. Coding regions that are necessary for the synthesis of key proteins which do not have paralogs elsewhere in the genome are lethal when removed. Conversely, coding regions with many paralogs or strongly expressed paralogs have a minimal effect on overall expression (especially trans regulatory expression) when removed. Singleton and duplicate capacitors both largely represent instances of incomplete functional redundancy; differentially expressed paralogs of duplicate capacitors continue some functionality of the original gene, and the protein-protein interaction complexes within which singleton capacitors reside largely exhibit overlapping functionality. In general the phenotypic capacitors identified by knockouts in yeast are genes expressed in several key regulatory areas which, while non-lethal when removed, do not have enough redundancy to maintain complete functionality. The concept of functional redundancy may also be involved in the high number of synthetic-lethal interactions which capacitor genes participate in. When a gene has its functionality resumed by a paralog or functional analog, its removal is not inherently lethal, however when the gene and its redundancy are removed, the result is lethality.


Simulations

Computational simulations of knockouts in complex gene interaction networks have demonstrated that many, and possibly all expressed genes have the potential to reveal phenotypic variation of some kind when removed, and that previously identified capacitor genes are simply especially strong examples. Capacitance, then, is simply a feature of complex gene networks that arises in conjunction with canalization.


Facultative sex

Recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
mutations can be thought of as cryptic when they are present overwhelmingly in
heterozygotes Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...
rather than homozygotes. Facultative sex that takes the form of selfing can act as an evolutionary capacitor in a primarily asexual population by creating homozygotes. Facultative sex that takes the form of
outcrossing Out-crossing or out-breeding is the technique of crossing between different breeds. This is the practice of introducing distantly related genetic material into a breeding line, thereby increasing genetic diversity. Outcrossing in animals Out ...
can act as an evolutionary capacitor by breaking up allele combinations with phenotypic effects that normally cancel out.


See also

* Canalization (genetics) *
Epigenetics In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...
* Preadaptation * Susan Lindquist


References

{{DEFAULTSORT:Evolutionary Capacitance Evolutionary biology Extended evolutionary synthesis Selection