Uncovering cryptic genetic variation

“In genetics, such external fluctuations could relate to the effects of cryptic genetic variation, which uncovers novel phenotypes under conditions of environmental change (Gibson & Dworkin 2004), thus potentially promoting increased robustness.”

“This is as true of threshold-dependent characters and cryptic variation”

“This “hidden” or “cryptic” variation can sometimes be revealed during the crossing process in transgressive segregation (deVicente and Tanksley, 1993; Xu et al., 1998; Gibson and Dworkin, 2004).”

“Genetic assimilation could also allow for the accumulation of cryptic genetic variation, which could later become expressed after removal of the canalizing factor, or “de-canalization,” thus promoting evolvability (Rutherford and Lindquist 1998, Gibson and Dworkin 2004; Flatt 2005).”

“…variation that may enable the creation of novelties through developmentalmediated mechanisms is “cryptic genetic variation,” so named because it is unexpressed in the phenotype of standing populations and thus normally hidden from selection (e.g., Gibson and Dworkin 2004; Lauter and Doebley 2002).”

“Why are some traits phenotypically invariant despite apparent genetic and environmental changes? Why are some traits less phenotypically variable in some taxa, but not in others? One of the most intriguing observations in evolutionary genetics is that wild-type populations often harbor vast amounts of hidden genetic v…”

“However, it is not clear how genetic and developmental systems can accumulate and store phenotypically neutral genetic variation while not expressing it (Wagner & Mezey 2000; Hermisson et al. 2003; Masel & Bergman 2003; Gibson & Dworkin 2004).”

“…through epistatic interactions with an evolving genetic background (Wagner et al. 1997), and is currently the focus of considerable theoretical and empirical interest (de Visser et al. 2003, Dworkin 2005a, Flatt 2005, Gibson & Dworkin 2004, Gibson & Wagner 2000, Rutherford 2000, Wagner 2005).”

“The basis of why these selection experiments seem to respond so well is still a matter of debate as to whether they do so from standing variation, new mutations, epigenetic changes (Gibson & Dworkin, 2004; Johannes et al., 2008) or a combination of the above.”

“The other focuses on gene networks and morphological traits in multicellular organisms, and uses the Waddingtonian metaphors of canalization, cryptic genetic variation, and genetic assimilation [8,17,18,20,21,23–25, 28, 32–34, 41–44, 74].”

“Such cryptic genetic variation is ubiquituous and it can affect phenomena as different as variation in genetic disease phenotypes and reproductive isolation.((5)) It is thus not surprising that biologists have a long-standing interest in robustness, going back to Fisher’s work on dominance,((6)) as well as to Waddingt…”

“Susceptibility variants will often be recently exposed cryptic factor”

“Exposing such cryptic genetic variation may have significant effects on the evolutionary trajectories of populations (Gibson and Dworkin 2004; Dworkin 2005a; Flatt 2005; Moczek 2007; Le Rouzic and Carlborg 2008; Schlichting 2008; McGuigan and Sgrò 2009; Masel and Trotter 2010; Draghi and Whitlock…”

“The release of cryptic genetic variation during shifts into novel or stressful environments has long been hypothesized to facilitate evolutionary change;((79,80)) relaxed selection on environment-specific genes may provide a general mechanism by which this variability accumulates.”

““Adaptive walks are shaped by CGV” (Gibson & Dworkin 2004).”

“Gibson and Hogness 1996), or mutations (Rutherford 2000; Gibson and Dworkin 2004).”

“Such cryptic genetic variation is pervasive but generally underestimate”

“For example, it might well be that biological systems are so robust against subtle genetic perturbations that the majority of heritable gene expression variation is effectively ‘‘buffered’’ and does not lead to downstream effects on other genes, protein, metabolites, or phenotypes [14–17].”

“However, exposing the population to new environments can reveal phenotypic differences and a lower degree of observed mutational robustness; a phenomenon known as CGV (Gibson and Dworkin, 2004).”

“vironmental stress is too great and robustness is compromised, “cryptic variation” is released (Gibson and Dworkin 2004).”

“In these cases, the transgressive effect is caused by epistasis in synergetic or antagonistic ways (Gibson and Dworkin, 2004; Carlborg et al., 2006).”

“Alternatively, a new environment can release cryptic genetic variation, rapidly altering heritable phenotypic variance and potentially shifting phenotypic means within a single generation (Gibson and Dworkin 2004; Le Rouzic and Carlborg 2008; Schlichting 2008), which, in turn, impacts the rate and nature of responses…”

“cryptic genetic variation in good health and disease [72].”

“2003, 2004; Barton & Turelli 2004; Gibson & Dworkin 2004) highlights the lack of basic data on the prevalence of nonadditive variance.”

“Such genetic variation can then fuel evolutionary change (Gibson and Dworkin, 2004; Ledón-Rettig et al., 2010; Paaby and Rockman, 2014; Schneider and Meyer, 2017).”

“One emerging theme is that development itself is a progenitor of phenotypic variation as it responds to environmental cues (in the present and past), thereby determining what heritable phenotypic variation is exposed to selection (West-Eberhard, 2003; Gibson & Dworkin, 2004).”

“Developmental buffering is an important factor in evolutionary processes, because it can maintain adaptive phenotypic traits in the presence of genetic and environmental variation and it can conceal genetic variation from selection [1–3].”

“…has concerned its genetic component (e.g., Visser et al. 2003), because it theoretically allows for the build up—and thus the occasional release—of cryptic genetic variation, potentially altering the pace of morphological evolution (Rutherford and Lindquist 1998; Gibson and Dworkin 2004).”

“In turn, such mutational robustness would result in genetic divergence of underlying developmental mechanisms without generating changes in the final phenotype (Gibson and Dworkin, 2004; Wagner, 2005).”

“Such variation in the growth environment can be used to uncover hidden genetic variation not expressed under control conditions and identify genes important for adaptation to environmental fluctuations [19].”

“Exposure to a novel or stressful environment may also be associated with a general increase in additive genetic variation (23).”

“THERE has recently been much interest in the abil-ity of evolutionary capacitors to tap into cryptic or hidden genetic variation and reveal a range of phenotypes (Rutherford and Lindquist 1998; True and Lindquist 2000; Queitsch et al. 2002; Bergman and Siegal 2003; Gibson and Dworkin 2004).”

“Many developmental systems produce outputs that are insensitive to a wide range of environmental or genetic perturbations. In these robust systems, buffering may allow for the accumulation of “cryptic” genetic variation affecting the system without changing its end product”

“2010), artificial selection in crops (Gibson and Dworkin 2004), viral pathogens (Pennings 2012), and invasive species (Prentis et al.”

“tions of alleles, both of which may expose genetic variation for phenotypes (Gibson and Dworkin 2004).”

“While many mutations in core metabolic processes will disrupt energy metabolism such that the phenotypic effects are manifest under all conditions, those mutations segregating in natural populations are more likely to cause inefficiencies in metabolism that are only revealed when temperature accelerates biological rat…”

“With epistasis, alleles have different effects in different genetic backgrounds, which causes variable allelic effects among individuals and populations 14 and affects the magnitude of expressed quantitative genetic variation 15 .”

“…thus on evolvability, has been suggested to contribute to patterns of evolutionary stasis in stable environments and rapid evolution in novel environments (Waddington 1957; Rutherford and Lindquist 1998; Gibson and Dworkin 2004; Badyaev 2005; Wagner 2005; Schlichting 2008; Masel and Siegal 2009).”

“Moreover, the accumulated genetic variation can be rapidly released and manifested in the face of further environmental or mutational changes, enabling rapid adaptive divergences [6,17,51,52].”

“The phenomenon of ‘cryptic variability’ that is only uncovered by genetic or environmental perturbations has been described in other systems and is thought to be an important modifier of phenotypic response [114].”

“Here, we explore the proximate mechanisms that facilitate the evolution of resource-use traits by considering the role of ‘cryptic’ genetic variation (sensu Gibson & Dworkin 2004; Schlichting 2008) in fuelling evolutionary shifts in resource use.”

“Epistasis is identified as a two-way statistical interaction between the variant (rover or sitter) and test genotype (mutant or control) [26] (see below).”

“Each of these partners, in turn, is likely to interact with a number of other proteins, analysis of sex-specific gene expression in two inbred strains (Gibson and Dworkin 2004) and also in individ-all of which are subject to regulation of their own.”

“This was most likely facilitated by a protein-protein interaction with Mcm1, which is conserved among S. cerevisiae and C. albicans, and may have helped stabilize Matα1 while its interaction with DNA slowly changed.”

“CGV is thought to be an important and pervasive, yet underappreciated, factor in the response of organisms to mutation, selection, and disease [34].”

“Moreover, environmental heterogeneity may sustain even more genetic variation than our best empirical studies suggest if much of the genetic variation arising from GEI is cryptic, and only observable once specific environmental perturbations arise (Gibson and Dworkin 2004).”

“Subsequent release of this CGV in an altered genetic or environmental background results in further phenotypic diversification (Gibson & Dworkin 2004) (Le Rouzic & Carlborg 2008) and may enhance reproductive isolation among populations (Pfennig et al. 2010; Fitzpatrick 2012).”

“thus altering their ability to contribute to a given population’s response to selection (Gibson and Dworkin 2004).”

“This indicates that the high fat environment exposes cryptic genetic variation for these traits (Gibson and Dworkin 2004; Gibson 2009).”

“Long-term fluctuations may produce phenotypic and developmental canalization (Meyers et al., 2005), but these populations could also accumulate cryptic genetic variation (Gibson & Dworkin, 2004).”

“Microevolutionary studies of cryptic genetic variation have so far been limited by the complexity of the trait used or by the lack of detailed molecular knowledge of the system (Gibson and van Helden 1997; Gibson et al. 1999; Gibson and Dworkin 2004; Zauner and Sommer 2007).”

“Gibson and Dworkin, 2004 ) in the fungal populations and the magnitude of selection acting on them.”

“…(Wagner and Altenberg 1996; Hadany and Beker 2003) or effects of a stressor on organism-wide homeostasis (Bradshaw and Hardwick 1989; Eshel and Matessi 1998; Schlichting and Pigliucci 1998; Gibson and Wagner 2000; Newman and Muller 2000; Nanjundiah 2003; Rutherford 2003; Gibson and Dworkin 2004).”

“A renewed interest in the importance of cryptic variation in evolution and human health highlights the importance of understanding canalization at the molecular level (Rutherford, 2000; Gibson & Dworkin, 2004).”