Cryptic genetic variation in a heat shock protein modifies the outcome of a mutation affecting epidermal stem cell development in C. elegans

A fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans. We demonstrate that a putative null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in phenotype expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 is sufficient to modify Wnt signalling and seam cell development, highlighting that natural variation in conserved heat shock proteins can shape phenotype expressivity.

Cryptic microgeographic variation in responses of larval Atlantic cod to warmer temperatures

Although temperature is known to drive species dynamics and distributions, our understanding of the extent to which thermal plasticity varies within species is poor. Differences in plasticity can arise through local adaptation to heterogeneous environments, hybridization, and the release of cryptic genetic variation in novel environments. Here, wild Atlantic cod (Gadus morhua) from contrasting environments inside and outside of a fjord system in southern Norway spawned freely in a semi-natural laboratory environment, generating pure crosses and reciprocal hybrids. A common-garden rearing experiment of the larvae at 6°C, 9.5°C, and 13°C revealed cryptic genetic variation in thermal responses of growth and survival at warmer temperatures. Variation in growth plasticity was greatest from 9.5°C to 13°C, the latter of which exceeds temperatures currently typical of larvae in their native environments. In contrast to our prediction of intermediate hybrid responses consistent with additive genetic effects, one reciprocal hybrid cross showed a 4% increase in size at the highest temperature, whereas most crosses exhibited 4-12% reductions in size. All crosses experienced severe (76-93%) reductions in survival from 9.5°C to 13°C. Variation in survival plasticity suggests a genetically variable basis for the severity with which survival declines with increasing temperature and the potential for an adaptive response to warming. Notably, we demonstrate the potential for hybridization between coexisting ‘fjord’ and ‘North Sea’ ecotypes that naturally inhabit the inner and outer fjord environments at contrasting frequencies. Yet, ecotype explained a minor (3-10%) component of growth reaction norm variation, suggesting it is insufficient for describing important biological variation. Current broad-scale management and lack of coastal monitoring impede the development of strategies to maintain the potential for adaptation to warming temperatures in systems with such phenotypic complexity resulting from cryptic genetic variation, coexisting ecotypes, and gene flow.

Cryptic genetic variation in a heat shock protein shapes the expressivity of a mutation affecting stem cell behaviour in C. elegans

A fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of key mutations. We address this question by focusing on the epidermal seam cells, which display stem cell properties in Caenorhabditis elegans. We demonstrate that a null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated and thus has lower expressivity in the divergent CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in mutation expressivity between the two isolates. These QTLs reveal cryptic genetic variation, which acts to reinforce seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 lowers egl-18 mutation expressivity. Our work underscores that natural variation in conserved heat shock proteins can shape mutation expressivity.

Cryptic genetic variation accelerates evolution by opening access to diverse adaptive peaks

Cryptic genetic variation can facilitate adaptation in evolving populations. To elucidate the underlying genetic mechanisms, we used directed evolution in Escherichia coli to accumulate variation in populations of yellow fluorescent proteins and then evolved these proteins toward the new phenotype of green fluorescence. Populations with cryptic variation evolved adaptive genotypes with greater diversity and higher fitness than populations without cryptic variation, which converged on similar genotypes. Populations with cryptic variation accumulated neutral or deleterious mutations that break the constraints on the order in which adaptive mutations arise. In doing so, cryptic variation opens paths to adaptive genotypes, creates historical contingency, and reduces the predictability of evolution by allowing different replicate populations to climb different adaptive peaks and explore otherwise-inaccessible regions of an adaptive landscape.

Cryptic genetic variation underpins rapid adaptation to ocean acidification

Global climate change has intensified the need to assess the capacity for natural populations to adapt to abrupt shifts in the environment. Reductions in seawater pH constitute a conspicuous stressor associated with increasing atmospheric carbon dioxide that is affecting ecosystems throughout the world’s oceans. Here, we quantify the phenotypic and genetic modifications associated with rapid adaptation to reduced seawater pH in the marine mussel, Mytilus galloprovincialis. We reared a genetically diverse larval population in ambient and extreme low pH conditions (pHT 8.1 and 7.4) and tracked changes in the larval size and allele frequency distributions through settlement. Additionally, we separated larvae by size to link a fitness-related trait to its underlying genetic background in each treatment. Both phenotypic and genetic data show that M. galloprovincialis can evolve in response to a decrease in seawater pH. This process is polygenic and characterized by genotype-environment interactions, suggesting the role of cryptic genetic variation in adaptation to future climate change. Holistically, this work provides insight into the processes underpinning rapid evolution, and demonstrates the importance of maintaining standing variation within natural populations to bolster species’ adaptive capacity as global change progresses.