Uncovering cryptic genetic variation

“The discovery of this additional layer of variation, known as cryptic genetic variation (for review, see Gibson & Dworkin 2004 ), has emphasized that simple Mendelian traits, as well as quantitative traits, can be influenced by complex genetic and environmental factors (for review, see Zlotogora 2003).”

“This is because robustness allows the accumulation of mutations (cryptic genetic variation [5]), and thus eventually ‘evolutionary innovation’, with minimal effects on fitness in the intervening time (reviewed in [6–8]), although the generality of this idea has been questioned [9].”

“The evolutionary importance of this phenomenon has recently received much attention (Rutherford 2003; Gibson and Dworkin 2004; Hoffmann and McKenzie 2005).”

“A modern interpretation of these results is that the stimulus exposed cryptic genetic variation, allowing selection for the constitutive expression of this trait (Rutherford & Lindquist 1998; Gibson & Dworkin 2004; Schlichting 2008).”

“Cryptic genetic variation is evolutionarily significant, because mutation or stress can unmask it, sometimes with dramatic phenotypic consequences [9,66,67].”

“Together, these results provide novel insights into the relationship between environmental change and developmental evolution and suggest that climate change may not expose large amounts of cryptic genetic variation to selection in this species.”

“Genetic polymorphisms are widespread in many populations [47,59], but the incidence of cryptic variation is usually unknown for wild populations [14,15].”

“The analysis of cryptic genetic variation has since been extended using quantitative genetics (Gibson and van Helden 1997; Polaczyk et al. 1998; Gibson and Dworkin 2004; Dworkin 2005b).”

“This scenario is very similar to the notion of cryptic genetic variation, or evolutionary capacitance, which is usually discussed in the context of eukaryotes [26-28].”

“Thus, an alternate view of how populations adapt to rapidly changing conditions suggests that the environment itself influences the phenotypic expression of genetic variation, thereby providing the raw material for adaptation to occur (Gibson and Dworkin 2004).”

“Thus, the idea of CGV largely holds to the same convention of general mutations in that variation is created randomly to facilitate the creation of phenotypic variation.”

“However, a new environment not only imposes new selection pressures, it also determines how standing genetic variation translates into the phenotypic variation upon which those selection pressures act (Gibson & Dworkin, 2004; Le Rouzic & Carlborg, 2008; McGuigan et al., 2010a; Schlichting, 2008).”

“Cryptic genetic variation — is genetic variation that is phenotypically silent until revealed by environmental, genetic, or epigenetic perturbations [8].”

“The environment likewise influences expressed genetic variation in a trait (Queitsch et al. 2002; Gibson & Dworkin 2004; Barrett & Schluter 2008; Barrett et al. 2009).”

“This observation suggests that cryptic genetic variation, a pool of genetic variation that does not result in phenotypic variation under “normal” conditions (Gibson and Dworkin, 2004; Paaby and Rockman, 2014), is prominent for the craniofacial skeleton.”

“An issue that population genetics faces when determining selection on novel genes, or how these novel genes may impact the phenotype, is that new genomic sequences may be modifiers of existing genes (Merlo and Boyle 2003), and may function via the release of cryptic variation (Gibson and Dworkin 2004).”

“stressed environmental conditions it clearly leads to a Chl retention phenotype suggesting cryptic genetic variation between these two genotypes [48, 49].”

“There is increasing molecular evidence from single-species studies to support the classification of intraspecific taxa without clear differentiation in the phenotype, that is cryptic species (Gibson and Dworkin 2004; Masel 2006; Bickford et al. 2007; Hayden et al. 2011; Schaefer et al. 2011), hence, SIE S is highly li…”

“These markers, which are distributed throughout the genome, can be used to analyze within-species diversity, infer demography, understand evolutionary processes, and uncover cryptic genetic variation (Gibson & Dworkin, 2004; Luikart, England, Tallmon, Jordan, & Taberlet, 2003).”

“For example, it may be that this variation is ‘‘cryptic’’ in the wild, and only becomes additive (selectable) in laboratory conditions [30].”

“regulatory changes) [18,19,20,21], (iii) if the recurrent appearance of this trait is caused by independent mutations or rather by introgression of standing genetic variation [22,23] or the release of cryptic genetic variation by changes in epistatic interactions [24,25], and (iv) how disruptive selection in dispersal…”

“However, in genetic assimilation, stress-induced phenotypes arise from cryptic genetic variation in populations [40] while, at least for the reinforced up-regulation of pntAB expression, the initial response required no standing genetic variation at all.”

“In Drosophila, many components of the sevens pathway that executes eye formation were identified using a genetically hypersensitive background generated by the ectopic expression of a component of the pathway (Gibson and Dworkin 2004).”

“Genetic diversity across orthologous proteins is thought to be predominantly neutral with respect to their native, physiological function, but can cause variation in other non-physiological phenotypic properties, a phenomenon known as ‘cryptic genetic variation’ (Le Rouzic and Carlborg, 2008; Gibson and Dworkin, 2004;…”

“…consist of (i) uncovering of new cryptic susceptibility variants that did not previously participate in the genetic architecture of the trait (Gibson and Dworkin, 2004), or (ii) an increase in the effect size of variants already associated with obesity before the emergence of the current…”

“…variance within the native rearing environment and that novel environments (i.e. environments where selection has not had an opportunity to historically act) result in the expression of increased variation (Gibson & Dworkin, 2004; Schlichting, 2008; McGuigan & Sgr o, 2009; McGuigan et al., 2010).”

“related species mainly involves either loci with small quantitative effects, or loci conferring no detectable phenotypic effect, known as cryptic variation [14–20].”

“Trait heritabilities, or the fraction of phenotypic variation due to additive genetic variation, also change greatly with environmental conditions (Gibson and Dworkin 2004; Schlichting 2008).”

“In sexual organisms, it is expected that robustness will directly increase the amount of hidden (‘‘cryptic’’) genetic variation within a population (Gibson and Dworkin, 2004).”

“Gene expression evolves under a house-of-cards model of stabilizing selection (Hodgins-Davis et al. 2015), maintaining population genetic variation (Jin et al. 2001; Gibson and Dworkin 2004; Nuzhdin et al. 2004).”

“…some of the possible phenotypes; a part of the population’s genetic variation is thus subject to relaxed selection and eventually accumulates despite not being expressed (Gibson and Dworkin, 2004; Le Rouzic and Carlborg, 2008; Lahti et al., 2009; Snell-Rood et al., 2010; Van Dyken and Wade, 2010).”

“Such cryptic variation can determine the consequences of both deleterious and beneficial second-site mutations and affects the success of breeding programs [7–9].”

“…recognize that penetrance of mutant phenotypes, trait heritabilities and trait covariance structures are all influenced by environmental conditions, and are thereby able to alter evolutionary trajectories, sometimes in profound ways (Stearns, 1989; Gibson and Dworkin, 2004; Schlichting, 2008).”

“merely accumulates deleterious alleles (Gibson and Dworkin, 2004; Paaby and Rockman, 2014; Zheng et al., 2019).”

“It does so by allowing the accumulation of genetic variation that is not observed phenotypically under typical conditions, but that may be exposed after non-genetic perturbations (de Visser et al., 2003; Gibson and Dworkin, 2004; Masel, 2006; Masel and Siegal, 2009).”

“An alternative explanation for the existence of parallel evolution in closely related lineages is that cryptic genetic variation that is present in the ancestral population is uncovered when the organism is exposed to a novel environment (Bell, 1974, 1988; Gibson and Dworkin, 2004 ).”

“Mutational variance, as defined by Gibson & Dworkin (2004), is the ‘tendency towards dispersion of data about the mean due to new mutations that arise in each generation.’”

“as a buffer to allow an organism exposed to an unexpected environmental stress, or to a de novo mutation, to resist the transition to alternative phenotypes.(6)”

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

“Previous studies have demonstrated the release of cryptic genetic variation after a genetic or environmental perturbation [2,9–16 , 20– 29 ].”

“This study thus supports the theoretical notion that disruption or destabilization of canalizing or homeostatic mechanisms can enhance phenotypic variability by releasing previously cryptic genetic variation (Gibson and Dworkin 2004; Suzuki and Nijhout 2006; WestEberhard 2003, 2005).”

“There is increasing evidence for the importance of cryptic and standing genetic variation in evolution (Gibson and Dworkin, 2004; Barrett and Schluter, 2007; McGuigan and Sgro, 2009) and no special mechanism is required for such variation to explain the convergent use of ancestral alleles in a new…”

“Populations can harbor significant cryptic genetic variation that has little or no phenotypic effect under normal conditions (Gibson and Dworkin 2004; Dworkin 2005).”

“Furthermore, selection for A under standard growing conditions of the Midwest in the United States would fail to select against deleterious alleles that confer sensitivity to elevated O3 (Gibson & Dworkin, 2004).”

“Finally, the F261Y mutation may also have been introduced through hybridization and introgression following backcrossing with other species (Gibson & Dworkin 2004).”

“First, under new selective pressures, the adaptive value of a preexisting allele can switch from neutral or deleterious to beneficial (Gibson and Dworkin 2004; Hermisson and Pennings 2005).”

“Under Waddington’s view, genetic assimilation is the result of selection on “cryptic” genetic variation, genetic variation that is not expressed in the ancestral environment—implicitly a form of nonadditive or epistatic gene interactions (16, 26).”

“This cryptic genetic variation (CGV) (Gibson and Dworkin, 2004; Schlichting, 2008; Hayden et al., 2011; McGuigan et al., 2011) may be expressed due to a breakdown in the mechanisms that suppress the influence of genetic variation on the phenotype, or to the accumulation of neutral mutations in unexpressed regions of t…”

“The fi rst reports of CGV arose largely through noticing that Drosophila mutations of interest appeared either suppressed or enhanced when crossed into diff erent inbred backgrounds that otherwise showed no noticeable mutant phenotype for the trait (Gibson and Dworkin, 2004).”

“For example, raising animals on artificial diets may result in unusually high levels of genetic variation because cryptic genetic variation in a novel (artificial) environment has been revealed (Gibson & Dworkin, 2004; Led on-Rettig et al., 2014).”

“Cryptic genetic variation is common, having been observed in a variety of systems for a variety of phenotypes [25,26].”

“…the uncovered intra- and interspecific variation in temperatureinduced developmental errors may be considered examples of cryptic genetic variation (Gibson and Dworkin 2004; Paaby and Rockman 2014) or developmental system’s drift (True and Haag 2001), that is, usually phenotypically invisible…”

“Several investigators have argued that, under stressful conditions, a cryptic genetic variability could be unravelled, leading to the possibility of a faster adaptive response (Bijlsma and Loeschcke 1997; Hoffmann and Parsons 1997; Rutherford and Lindquist 1998; Gibson and Dworkin 2004).”

“…novel environments, result in the release of cryptic genetic variation, alter the mean and variance of phenotypes on which selection can then act and facilitate rapid adaptation (Gibson and Dworkin, 2004; Lande, 2009; Le Rouzic and Carlborg, 2008; Schlichting, 2008; Scoville and Pfrender, 2010).”

“Hidden (or cryptic) genetic variation is defined as "standing genetic variation 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 or the introduction of novel alleles [49].”

“The large differences in number of DMCs we found between lines could be explained by their genetic differences [39].”

“Hidden variations due to the linked QTLs Cryptic genetic variation is uncovered by environment or genetic perturbations, and is thought to be increasingly relevant in quantitative traits (Rieseberg et al. 1999; Mackay 2001; Gibson & Dworkin 2004).”

“In hindsight, many features of living things are evolutionary capacitors or render genetic variation cryptic (Gibson and Dworkin, 2004; Masel, 2006).”

“One possible consequence is that the measured phenotypes have been decanalized and some of the QTL we observed may correspond to cryptic genetic variation [45, 46, 69] that only influence traits in the presence of the lit/litmutation.”

“…Armin P. Moczek, Department of Biology, Indiana University, 915 East Third Street, Bloomington, IN 47405-7107, USA e-mail: armin@indiana.edu This manuscript reviews our growing understanding of the role of environmental conditions in shaping development and developmental evolution.”

“nalisation, could have been disrupted, permitting the expression of underlying cryptic genetic variation from natural selection or mutation [32].”

“Cryptic genetic variation (CGV) is ubiquitous and abundant among organisms (Schlichting 2008; Masel & Trotter 2010), and it might be an important source of physiological and evolutionary potential (Gibson & Dworkin 2004).”