Uncovering cryptic genetic variation

“We discuss these results from the practical perspective of the scale of measurement of the trait and from the more theoretical perspective of the question of whether loci that affect standing phenotypic variation also harbor cryptic genetic variation (Gibson and Dworkin 2004).”

“The thoughts have been shaped by our post-doctoral experiences two decades apart, working with Drosophila melanogaster and Caenorhabditis elegans, attempting to bridge the gap between micro- and macro-evolution [1,2].”

“The evolution of canalization and developmental stability has been studied in the context of quantitative genetics, both experimentally and theoretically.(10,11) Both approaches rely on a precise decomposition of phenotypic variation and have in common that they do not require any precise understanding of the proximal…”

“By storing genetic variation that is not exposed to selection under normal circumstances, Hsp90 may act as a capacitor for evolution (Rutherford and Lindquist 1998; Rutherford 2000, 2003; Ruden et al. 2003; Gibson and Dworkin 2004).”

“Other studies have found cryptic genetic variation in scutellar bristle number and photoreceptor patterning 177 .”

“However, in some cases, new mutations appear to interact with “cryptic” variants that do not typically influence phenotype (Gibson and Dworkin 2004; Paaby and Rockman 2014), suggesting that major epistatic effects can involve variants that lack additive effects.”

“Regardless of the process involved, it has been suggested that stressful environmental conditions, as well as pleiotropic mutations, might destabilize the developmental process and lead to the uncovering of cryptic genetic variation (Gibson and Dworkin 2004; Schlichting 2008).”

“Rearing experiments at abnormally high temperatures may reveal cryptic plasticity (Gibson & Dworkin, 2004) but may not be as useful in determining actual responses to expected temperature change.”

“…variance available to selection under ordinary environmental circumstances that characterise populations rich in singing, normal-wing males, but with increasing exposure of cryptic genetic variation as the social environment shifts due to the proliferation of flatwing males (Gibson & Dworkin 2004).”

“’ Much of the motivation behind research into this phenomenon lies in its potential to facilitate adaptive evolution, by increasing the additive genetic variance available to selection [65, 66].”

“A common mechanism for balancing stability and instability at phenotypic levels is known as developmental stability, which is intimately related to canalization or robustness (Debat and David, 2001; Gibson and Dworkin, 2004).”

“Alternatively, it is possible that Dll remains a source of cryptic genetic variation for this trait (Gibson and Dworkin 2004).”

“(Mayr 1954; Fisher 1958; Wright 1968, 1977; Wallace 1991; Gibson & Dworkin 2004; Phillips 2008; Paaby & Rockman 2014; Paaby & Gibson 2016; Yadav, Dhole & Sinha, 2016).”

“…with genetic samples, which underlies the pivotal role that landscape and space plays in: (i) structuring populations (Slatkin 1985), (ii) generating cryptic genetic diversity (Gibson & Dworkin 2004) and (iii) ultimately influencing speciation and regional patterns of*Correspondence author.”

“It is also possible that this molecular variation may be a source of "cryptic" genetic variation that could be exposed by changing environments (Gibson and Dworkin 2004), and thus accelerate adaptation in changing environments.”

“Cryptic genetic variations are hidden genetic variations that do not affect the trait in a given genetic background or environmental condition, but may be expressed after environmental, genetic, or epigenetic perturbations (Gibson and Dworkin, 2004).”

“Genetic differences between control and selection lines that are responsible for adaptation to the treatments did not have an effect in control conditions and thus represent cryptic genetic variation (Gibson & Dworkin, 2004).”

“Such evolution has been called various names, such as developmental drift [23], cryptic variation [24] or phenotypically neutral [25], all being agnostic as to the selective context.”

“Cryptic genetic variation can provide a source of evolutionary potential when uncovered by environmental or genetic perturbations [54,55], and thereby can expedite evolutionary change.”

“Instead, variation in male preferences may be cryptic variation rarely expressed in natural populations, revealed only by the inbreeding process and/ or a novel environmental context [45].”

“CGV is defined as standing genetic variation that has no impact on phenotype or fitness under normal conditions, but which is expressed under stressful or novel conditions [95, 96].”

“This classical theory has been reinvigorated by pan-genomics, which is revealing pervasive variation within gene families, cis -regulatory regions and regulatory networks 4–6 .”

“It may be that lola plays a non-essential role in the regulation of processes directing wing margin development, which only becomes apparent when Cut activity is decreased, akin to the cryptic variations necessary for evolutionary adaptations (GIBSON and DWORKIN 2004).”

“The rate of stochastic tunneling depends strongly on the population size (Iwasa et al. 2004; Weissman et al. 2009).”

“As a result, occasionally expressing alternative phenotypes by environmental noise might help speed adaptation via ‘genetic assimilation’ – that is, by promoting those individuals who will subsequently evolve the adaptive phenotype by mutation (Ancel and Fontana, 2000; Earl and Deem, 2004; Gibson and Dworkin, 2004; Ma…”

“Such genetic variation that does not translate into phenotypic variation is often termed hidden or cryptic genetic variation (Gibson and Dworkin 2004).”

“…of complex traits (Carlborg et al. 2006; Chandler et al. 2014; Chari & Dworkin 2013; Clark & Wang 1997; Doebley et al. 1995; Gaertner et al. 2012; Gibson & Dworkin 2004; Hanlon et al. 2006; Huang et al. 2012; Jarvis & Cheverud 2011; Kroymann & Mitchell-Olds 2005; Leamy et al. 2011; Mackay 2014;…”

“…genetic variation has been defined as the part of a population's standing genetic variation that has no effect on the phenotypic variation in a stable environment but can increase heritable variation in environmental conditions rarely experienced (Gibson & Dworkin, 2004; Paaby & Rockman, 2014).”

“2009), “pervasive robustness in biological systems” (Félix and Barkoulas 2015) or canalization (Waddington 1957; Gibson and Dworkin 2004).”

“Under a model of stabilizing selection, gene expression becomes canalized whereby the effects of genetic variation on gene expression is buffered to minimize variation (Gibson and Wagner 2000; Gibson and Dworkin 2004).”

“Canalization is the process by which phenotypic variation under a given perturbation is reduced, for example due to suppression of the expression of genetic variation (Gibson and Dworkin, 2004).”

“Replacing an allele that confers less sensitivity to mutational effects with one that confers more sensitivity (or introducing an environmental perturbation with similar effect) will cause the accumulated variation to have phenotypic consequences ([4, 5]).”

“…due to shared evolutionary history, we used the phylogeny of Lovette et al. (2010) for relationships among wood warblers (Parulidae) and that of Gibson and Baker (2012) for relationships among shorebirds (Scolopacidae), both with Pagel's arbitrary branch lengths (Pagel, 1992; calculated with…”

“The assessment of the genetic dimension of biodiversity allows the identification of evolutionarily significant units and an understanding of species’ adaptive potential (e.g. Gibson & Dworkin, 2004; Paaby & Rockman, 2014).”

“Our study provides a comprehensive window into the environmental dependency of the human transcriptome, including genetic effects that are only revealed by environmental change — a class of variants known as “ cryptic genetic variation ” (Gibson and Dworkin 2004; Paaby and Rockman 2014).”

“Natural genotypes often harbour extensive CGV that is only released upon severe environmental or genetic perturbations [43–45].”

“…an ancestral population, providing trajectories for selection to act upon and a mechanism by which plasticity can influence evolutionary outcomes (Gibson & Dworkin 2004; Le Rouzic & Carlborg 2008; Schlichting 2008; McGuigan & Sgró 2009; McGuigan et al. 2011; Ledón-Rettig et al. 2014; Paaby &…”

“Variation in a developmental system that is buffered at the level of the system output is often called cryptic variation (Gibson and Dworkin 2004).”

“15 While GWAS have been used to uncover disease-specific mutations, a recent study has suggested the clinical importance of cryptic mutations to understand disease development.”

“Third, the existence of such cryptic genetic variation is evidence that the developmental system is capable of buffering substantial genetic variation without altering the phenotype (Gibson and Dworkin, 2004; Wagner, 2007).”

“GEI may also be important for phenotypic evolution, as it is proposed to unmask cryptic variation for traits otherwise buffered from change through canalization (Waddington 1942; Gibson and Dworkin 2004).”

“…variation may be sensitive to environmental triggers, it acts as a source of innovation that can be episodically induced and presented to selection (Gibson & Dworkin, 2004; Levis & Pfennig, 2016; McGuigan & Sgrò, 2009; Moczek, 2008; Paaby & Rockman, 2014; Schlichting, 2008; Schwab et al., 2019;…”

“Both trait variance and repeatability—the latter defined as the proportion of observed variance attributable to consistent among individual differences—are known to change in response to environmental conditions (Gibson and Dworkin, 2004; Norin et al., 2016).”

“…that does not contribute to the normal range of phenotypes observed in a population, but that is available to modify a phenotype that arises after environmental change…” (Gibson and Dworkin, 2004), with “standing genetic variation” defined as the existence of more than one allele for a trait.”

“An adapted population is not genetically constant, instead it continues to accumulate genetic variants phenotypically neutral in that selection condition (Gibson and Dworkin 2004).”

“These mutations or polymorphisms generally don’t contribute to the normal range of phenotypes observed in a population, but are thought to have a role in modifying a phenotype that arises after environmental change or the introduction of novel alleles (Gibson and Dworkin, 2004).”

“sources: Genetic diversity (polymorphism) within populations can produce variation in gene expression levels and in the activity of gene products [9–13].”

“…limits variation from the phenotypic norm, it may favour genotypes that produce the same beneficial phenotype even in the presence of perturbations (Schmalhausen, 1949; Waddington, 1957; Travis, 1989; Rice, 1998; Gibson & Dworkin, 2004; Schlichting, 2008; Landry, 2009; Paaby & Rockman, 2014).”

“Cryptic variation has further important consequences (not discussed here), as it may be uncovered by further mutation or a new environmental change.((24))”

“This has implications not only for the relationship between genotype and phenotype, but also for evolution (Gibson and Wagner 2000; Gibson and Dworkin 2004; Wagner 2012).”

“…is the regulation of cryptic genetic variation, which refers to genetic variants that show their effects only in certain genetic backgrounds or environments and are phenotypically neutral in others (Gibson & Dworkin, 2004; Gibson & Reed, 2008; Masel & Trotter, 2010; Paaby & Rockman, 2014).”

“Such epistatic interactions of novel allelic combinations generated in arti fi cial C. elegans populations are thus particularly likely to affect traits that involve a polygenic architecture 4,17,79,97,98 .”

“In this case, substantial additive genetic variation can be produced by mutation even when genes have strong interactions at the molecular level of genes and their products, termed functional epistasis (Stadler et al. 2000; Gibson and Dworkin 2004; Phillips 2008).”

“Moreover, because some of this variation may be “cryptic” (i.e., genetic variation that is not normally expressed as phenotypic variation under an organism’s standard conditions but is expressed under unusual conditions; Gibson and Dworkin, 2004), competitively induced plasticity may expose standing genetic variation…”

“However, it is critical to recognize that populations typically segregate for myriad quantitative traits (Mackay, Stone, & Ayroles, 2009) and the expression of these phenotypes can also be affected by the introduction of mutations (Gibson & Dworkin, 2004; Paaby & Rockman, 2014).”

“This provides a mechanism to maintain or “hide” large amounts of polymorphism and avoid the cost of genetic variation (Gibson and Wagner 2000; Gibson and Dworkin 2004; Kitano 2004; Proulx and Phillips 2005; Proulx et al. 2007).”