"Bet hedging" against climate change in developing and adult animals: roles for stochastic gene expression, phenotypic plasticity, epigenetic inheritance and adaptation

Abstract

Animals from embryos to adults experiencing stress from climate change have numerous mechanisms available for enhancing their long-term survival. In this review we consider these options, and how viable they are in a world increasingly experiencing extreme weather associated with climate change. A deeply understood mechanism involves natural selection, leading to evolution of new adaptations that help cope with extreme and stochastic weather events associated with climate change. While potentially effective at staving off environmental challenges, such adaptations typically occur very slowly and incrementally over evolutionary time. Consequently, adaptation through natural selection is in most instances regarded as too slow to aid survival in rapidly changing environments, especially when considering the stochastic nature of extreme weather events associated with climate change. Alternative mechanisms operating in a much shorter time frame than adaptation involve the rapid creation of alternate phenotypes within a life cycle or a few generations. Stochastic gene expression creates multiple phenotypes from the same genotype even in the absence of environmental cues. In contrast, other mechanisms for phenotype change that are externally driven by environmental clues include well-understood developmental phenotypic plasticity (variation, flexibility), which can enable rapid, within-generation changes. Increasingly appreciated are epigenetic influences during development leading to rapid phenotypic changes that can also immediately be very widespread throughout a population, rather than confined to a few individuals as in the case of favorable gene mutations. Such epigenetically-induced phenotypic plasticity can arise rapidly in response to stressors within a generation or across a few generations and just as rapidly be "sunsetted" when the stressor dissipates, providing some capability to withstand environmental stressors emerging from climate change. Importantly, survival mechanisms resulting from adaptations and developmental phenotypic plasticity are not necessarily mutually exclusive, allowing for classic "bet hedging". Thus, the appearance of multiple phenotypes within a single population provides for a phenotype potentially optimal for some future environment. This enhances survival during stochastic extreme weather events associated with climate change. Finally, we end with recommendations for future physiological experiments, recommending in particular that experiments investigating phenotypic flexibility adopt more realistic protocols that reflect the stochastic nature of weather.

Keywords: climate change; development; phenotypic plasticity; stochasticity; weather.

FIGURE 1

Research focus on Physiology, Climate Change and Developmental Physiology. Results are shown for an August 2023 search of the PubMed data base (https://pubmed.ncbi.nlm.nih.gov/). (A) Search terms = “climate change” and “extreme weather”. (B) Search terms = “stable environment” and “unstable environment”. (C) Search terms = “physiology” and “climate change” and indicated developmental category such as “larva”. (D) Search terms = “physiology” and “climate change” and “development” and indicated environmental variable such as “temperature”. While only very generally indicative of the papers in the PubMed data base, these searches indicate that the great preponderance of studies focus on the effects of incremental (non-fluctuating) temperatures associated with climate change.

FIGURE 2

Mechanisms for phenotypic change over time. Left Panel: Developmental Phenotypic Plasticity acts within the span of a single generation. Both stochastic gene expression and developmental phenotypic plasticity during development can create different phenotypes within a population. In this example, each colt has a different dappling pattern, which can also change during further development. Middle Panel: Transgenerational epigenetic inheritance of a modified phenotype results from the actions of so-called readers, writers, eraser and enhancers on the epigenome which, in turn, results in modified gene expression in the F₁ generation (and potentially additional generations). Here, the dappling pattern of the mother’s colt may reflect changes in gene expression rather than changes in gene sequence. Right Panel: ‘Classic’ Mendelian Inheritance of modified phenotype results from inheritance of a set of alleles typically inherited from both male and female parents (P₀s) across an evolutionary time scale. This example shows the evolution of height and other features from Hyracotherium (dawn horse) to modern day horses (Equus caballus) over ∼50 million years.

FIGURE 3

Natural selection occurs throughout ontogeny as well as across generations. Though sometimes ignored, it is important to emphasize that natural selection acts on all developmental stages (vertically arrows), not just adults across generations. Thus, evolution is properly viewed as including change in a series of ontogenies, not just evolutionary change in adults of a population or species across evolutionary time (horizontal arrows).

FIGURE 4

Phenotypic plasticity in the onset of air breathing in two sister-species of labyrinth fishes. (A) In response to decreasing levels of aquatic oxygen, the three-spot gourami (Trichopodus trichopterus) delays the onset of air breathing. (B) In contrast, the Siamese fighting fish (Betta splendens) accelerates the onset of air breathing as larvae during varying degrees of hypoxic exposure (Data from Mendez-Sanchez and Burggren (2014)). Larvae of both species thus show developmental phenotypic plasticity, even though the responses to the same stressor (hypoxia) are in opposite directions.

FIGURE 5

Analogy for understanding rebound of epigenetically-produced phenotypes in variable environments. (A) The punching bag on its spring stand (organism) remains in a stable, default configuration (normal phenotype) when it is not being punched (environmental stressor). (B) When punched, the bag will assume a new configuration (epigenetically modified phenotype) that will be maintained as long as the punching continues. (C) When punching stops (stressor dissipates), the punching bag rebounds to its previous configuration (normal phenotype).

FIGURE 6

Phenotype switching. (A) Phenotypic switching by point mutation (A-F) vs. inheritance through effects of the epigenome on gene expression (1–6). Survival by point mutation (A-F): During mild environmental conditions, there is no selection pressure towards a modified phenotype with greater heat tolerance (A). Upon the appearance of elevated environmental temperature, in this example for three generations, there may be a strong selection pressure favoring favorable but rare point mutations that enhance heat tolerance. The very small proportion of individuals in the general population with this mutation are heavily selected for, but this mutation like most mutations only very slowly begins to be fixed in the general population (B-C, red dashed line). However, when elevated environmental temperature dissipates, this heat-tolerant mutation may confer no advantage and may even be detrimental under conditions of normal environmental temperature. Thus, individuals with this mutation may be selected against, resulting in slow decrease of this mutation in the general population (D). This cycle of positive and negative natural selection may be repeated with future alternating periods of environmental high temperature (E-F). Survival by epigenetic modification of gene expression–i.e., ‘epigenetic inheritance’ (1–6): During mild environmental conditions, there is no stimulus for changes in the epigenome that would create a modified phenotype with greater heat tolerance (1). Upon the appearance of elevated environmental temperature, however, there may be a change in pattern of epigenetic markers, resulting in changes in gene expression that confer enhanced heat tolerance. Importantly, this change in gene expression leading to greater survival in hot conditions is likely to occur in a large proportion of the population if not the entire population (2), unlike point mutations producing a heat tolerant phenotype that occur only in a few individuals at a time. This favorable phenotype produced by modified gene expression can continued to be epigenetically inherited across multiple generations as long as hot conditions exist. However, when elevated environmental temperature dissipates, the phenotype “washes out” as the epigenome and gene expression return to their normal configuration (3), and the heat-tolerant phenotype rapidly disappears in the general population. Just as for Mendelian inheritance, this cycle of epigenetic inheritance may be repeated (4–6) when another extended period of environmental high temperature returns (Adapted from Burggren (2016), licensed under CC BY 4.0). (B) Hypothetical changes in epigenetically modified phenotype over multiple generations. In this model, the epigenetically modified phenotype can arise fully in the F1 generation, and then fade out over subsequent generations (‘wash out’). Alternatively, the effect can appear in the F1 or even not until the F2 generation (‘wash in’), and then grow over subsequent generations before eventually fading (‘washout’). Empirical evidence supports both scenarios. Modified with permission from Burggren, (2015).

FIGURE 7

Bet hedging in a population through simultaneous multiple phenotypes. (A) This hypothetical example shows the changing relative fitness of three different populations as environmental temperature increases. The (−) population lacks any individuals with a heat tolerant phenotype. While its fitness in the absence of short-term temperature increases is higher, it experiences the greatest reduction in fitness as temperature increases above ‘normal’. The second population (+), possesses large numbers of individuals with the heat tolerant phenotype. Its overall fitness at lower temperatures is much lower than the (−) population lacking individuals with the heat tolerant phenotype, reflecting the heat-intolerant individuals elevated costs at these lower temperatures. However, as a consequence, this population with its heat tolerant individuals has a greater overall fitness as temperature increases up to a point at which no phenotype survives. This is an example of bet hedging in which the (+/−) population that has significant numbers of both heat tolerant (+) and heat intolerant (−) individuals has only intermediate fitness, but it will have some surviving individuals irrespective of whether temperature increases or stays constant. (B) This example shows how bet hedging can assist during development. As with example A), a heat-tolerant (+), heat-intolerant (−) and bet hedging population (+/−) are compared. All three populations decline in early development, reflecting natural mortality associated with the development process. Overall, however, the bet hedging population survives at a higher rate than the heat-intolerant population, but not as well as the heat-tolerant population. Thus, as in typical bet hedging, irrespective of whether there is a short-term temperature increase, the population with both phenotypes fairs better than the population without the (+) heat-tolerant phenotypic variation.

FIGURE 8

Experimental protocols in climate-related research that have been used to test biological responses to environmental challenges. (A) A simple step-wise change in conditions (e.g., from an acclimation temperature of 20°C to a new stable temperature 25°C) remains the most commonly employed protocol, in part because it is the most traditional, most easily interpreted and also the easiest to perform. (B–D) show variations on the theme of changing and environmental variable that begin to approach the complexity of natural environments. (E, F) indicate approaches with cyclic transitions, that can somewhat accurately represent the average temperature changes associated with diel, tidal or seasonal changes. (G, H). Imposing stochastic changes on cyclic or other protocols is simultaneously the most realistic (at least for terrestrial and small freshwater ecosystems), yet is also the most difficult to simulate. See text for further discussion. Reproduced from Burggren (2019), with permission from the American Physiological Society.