Ecological and evolutionary consequences of anticancer adaptations

Authors: Justine BOUTRY; Antoine DUJON; G.E.R.A.R.D. Anne-Lise; Sophie TISSOT; Nick MACDONALD; Aaron SCHULTZ; Peter A. BIRO; Christa BECKMANN; Rodrigo HAMEDE; David G. HAMILTON; Mathieu GIRAUDEAU; Beata UJVARI; Frédéric THOMAS

Source: iScience (Oct 2020)

Brief summary of the paper:

Cellular cheating leading to cancers exists in all branches of multicellular life, favoring the evolution of adaptations to avoid or suppress malignant progression, and/or to alleviate its fitness consequences.

Ecologists have until recently largely neglected the importance of cancer cells for animal ecology, presumably because they did not consider either the potential ecological or evolutionary consequences of anticancer adaptations.

Here, we review the diverse ways in which the evolution of anticancer adaptations has significantly constrained several aspects of the evolutionary ecology of multicellular organisms at the cell, individual, population, species and ecosystem levels, and suggest some avenues for future research.

Long term effects of outbreeding: experimental founding of island population eliminates malformations and improves hatching success in sand lizards

Authors: Willow R. Lindsay; Thomas Madsen; Erik Wapstra; Mette Lillie; Lisa Loeb; Beata Ujvari; Mats Olsson

Source: BIOLOGICAL CONSERVATION (Jul 2020)

Brief summary of the paper:

Loss of genetic variation is an increasing problem in many natural populations as a result of population fragmentation, inbreeding, and genetic drift, which may lead to inbreeding depression and subsequent “extinction vortices”. In such cases, outbreeding offers a potential population saviour from extinction.

Here we compare offspring viability between an experimentally founded outbred island population of sand lizards Lacerta agilis, and an inbred mainland source population on the Swedish West coast.

We have studied the mainland population for over a decade during which >4000 offspring from >500 parents were monitored. We conducted an outbreeding experiment in which lizards from the mainland population with relatively low genetic variation were crossbred with lizards from distant populations that lack gene flow.

The resulting 454 offspring were introduced to an otherwise uninhabited island with ideal sand lizard habitat. A survey of the island two decades later showed that offspring produced by females from the experimentally founded population had 13% higher hatching success (99.3% versus 86.4%) and elimination of the malformations occurring in 21% of clutches in the mainland source population.

These results co-occur with higher genetic diversity. We conclude that outbreeding improved offspring viability in our island population ca 5–6 generations after the founding event, that is, with sustained viability effects at a time when heterotic effects are expected to have subsided.

Darwin, the devil, and the management of transmissible cancers

Authors: Rodrigo Hamede; Thomas Madsen; Hamish McCallum; Andrew Storfer; Paul A. Hohenlohe; Hannah Siddle; Jim Kaufman; Mathieu Giraudeau; Menna Jones; Frédéric Thomas & Beata Ujvari

Source: Conservation Biology (SEP 2020)

Brief summary of the paper:

Evolutionary processes related to pathogens and functional genomics provide new tools for infectious disease management in the wild.

The ecology and evolution of wildlife cancers: Applications for management and conservation

Authors: Rodrigo Hamede, Rachel Owen, Hannah Siddle, Sarah Peck, Menna Jones, Antoine M. Dujon, Mathieu Giraudeau, Benjamin Roche, Beata Ujvari, Frédéric Thomas

Source: Evolutionary Applications (MAR 2020)

Brief summary of the paper:

Ecological and evolutionary concepts have been widely adopted to understand host–pathogen dynamics, and more recently, integrated into wildlife disease management.

Cancer is a ubiquitous disease that affects most metazoan species; however, the role of oncogenic phenomena in eco‐evolutionary processes and its implications for wildlife management and conservation remains undeveloped.

Despite the pervasive nature of cancer across taxa, our ability to detect its occurrence, progression and prevalence in wildlife populations is constrained due to logistic and diagnostic limitations, which suggests that most cancers in the wild are unreported and understudied. Nevertheless, an increasing number of virus‐associated and directly transmissible cancers in terrestrial and aquatic environments have been detected. Furthermore, anthropogenic activities and sudden environmental changes are increasingly associated with cancer incidence in wildlife.

This highlights the need to upscale surveillance efforts, collection of critical data and developing novel approaches for studying the emergence and evolution of cancers in the wild. Here, we discuss the relevance of malignant cells as important agents of selection and offer a holistic framework to understand the interplay of ecological, epidemiological and evolutionary dynamics of cancer in wildlife.

We use a directly transmissible cancer (devil facial tumour disease) as a model system to reveal the potential evolutionary dynamics and broader ecological effects of cancer epidemics in wildlife. We provide further examples of tumour–host interactions and trade‐offs that may lead to changes in life histories, and epidemiological and population dynamics.

Within this framework, we explore immunological strategies at the individual level as well as transgenerational adaptations at the population level. Then, we highlight the need to integrate multiple disciplines to undertake comparative cancer research at the human–domestic–wildlife interface and their environments.

Finally, we suggest strategies for screening cancer incidence in wildlife and discuss how to integrate ecological and evolutionary concepts in the management of current and future cancer epizootics.

Spontaneous activity rates and resting metabolism: Support for the allocation model of energy management at the among‐individual level

Authors: Peter A. Biro, Frédéric Thomas, Beata Ujvari, Bart Adriaenssens & Christa Beckmann

Source: ETHOLOGY (JAN 2020)

Brief summary of the paper:

Despite continuing interest in the proximate energetic constraints on individual variation in behavior, there is presently equivocal evidence for correlations between metabolism and behavior at the among‐individual level.

Possible reasons for this include imprecise estimates of individual mean behavior and metabolism due to no repeated measures on one or more of the traits, analyses that do not take into account the labile nature of these traits and the uncertainty in individual estimates, and changing environmental conditions not accounted for.

Predicted mean values for individual activity rate and resting metabolic rate (RMR), and associated SE’s for each, as extracted from the bivariate mixed‐effects model. Values are expressed as deviations from the mean level model and are in units of standard deviations due to data standardization to mean zero and SD = 1. The overall average mass‐corrected RMR was 184 mg O2/g/h (range = 138–240 among individuals)

In this empirical study, we repeatedly measured activity rates and resting metabolic rates (RMR) of individual male mosquitofish over an extended period, lasting several months under constant laboratory conditions. Repeatability of each trait was significant (RMR:  = .41; activity:  = .72), indicating consistent variation among individuals, making covariance between them possible. Contrary to expectations, bivariate mixed model analysis revealed that more active individuals had lower RMR ( = −.58) after accounting for mass effects and other covariates.

This result suggests that high activity rates require individuals to allocate less energy toward maintenance, and thus provides evidence for the “allocation” model of energy management. We suggest that it would be valuable to study whether and how behavior‐RMR correlations change over individual lifetime, a topic that has yet to be addressed.

Cancer and mosquitoes – An unsuspected close connection

Authors: Audrey Arnal, Benjamin Roche, Louis-Clément Gouagna, Antoine Dujon, Beata Ujvari, et al.

Source: Science of The Total Environment (JUN 2020)

Graphical abstract:

Brief summary of the paper:

Cancer is a major public health issue and represents a significant burden in countries with different levels of economic wealth. In parallel, mosquito-borne infectious diseases represent a growing problem causing significant morbidity and mortality worldwide.

Acknowledging that these two concerns are both globally distributed, it is essential to investigate whether they have a reciprocal connection that can fuel their respective burdens. Unfortunately, very few studies have examined the link between these two threats.

This review provides an overview of the possible links between mosquitoes, mosquito-borne infectious diseases and cancer.

We first focus on the impact of mosquitoes on carcinogenesis in humans including the transmission of oncogenic pathogens through mosquitoes, the immune reactions following mosquito bites, the presence of non-oncogenic mosquito-borne pathogens, and the direct transmission of cancer cells.

The second part of this review deals with the direct or indirect consequences of cancer in humans on mosquito behaviour.

Thirdly, we discuss the potential impacts that natural cancers in mosquitoes can have on their life history traits and therefore on their vector capacity. Finally, we discuss the most promising research avenues on this topic and the integrative public health strategies that could be envisioned in this context.

Predation shapes the impact of cancer on population dynamics and the evolution of cancer resistance

Authors: Cédric Perret; Cindy Gidoin; Beata Ujvari; Frédéric Thomas & Benjamin Roche

Source: EVOLUTIONARY APPLICATIONS (June 2020)

Brief summary of the paper:

Cancer is a widespread disease that affects most of the metazoans. However, cancer development is a slow process and, long before causing the death of the individual, may weaken organisms’ capacities and impair their interactions with other species.

Yet, the impact of cancer development on biotic interactions, and over the dynamics of the whole ecosystem, is still largely unexplored. As well, the feedback of altered biotic interactions on the evolution of resistance against cancer in the context of community ecology has not been investigated.

From this new perspective, we theoretically investigate how cancer can challenge expected interaction outcomes in a predator–prey model system, and how, in return, these altered interaction outcomes could affect evolution of resistance mechanism against cancer.

First, we demonstrate a clear difference between prey and predator vulnerability to cancer, with cancer having a limited impact on prey populations. Second, we show that biotic interactions can surprisingly lead to a null or positive effect of cancer on population densities.

Finally, our evolutionary analysis sheds light on how biotic interactions can lead to diverse resistance levels in predator populations. While its role in ecosystems is mostly unknown, we demonstrate that cancer in wildlife is an important ecological and evolutionary force to consider.

The interface between ecology, evolution, and cancer: More than ever a relevant research direction for both oncologists and ecologists

Authors: Frédéric Thomas; Benjamin Roche; Mathieu Giraudeau; Rodrigo Hamede & Beata Ujvari

Source: EVOLUTIONARY APPLICATIONS (June 2020)

Brief summary of the paper:

Forty years ago, scientists started to describe the genetic cascade of events leading to cancer as “somatic evolution”. Even if the full relevance of these pioneer papers was not immediately perceived by the scientific community, they paved the way for one of the most stimulating and challenging research directions in the effort to predict cancer emergence, progression, and therapy outcomes.

Evolutionary biology has indeed deeply transformed our understanding of cancer, gaining unprecedented international recognition among oncologists in the last decade. Nowadays, cancer is widely considered as a pathology that emerges due to clonal evolution and cell competition, Darwinian selection being the driver of cancer cells along selective landscapes, culminating in resistance to immune attack, malignant progression, resistance to therapies, metastasis, and even sometimes contagion between individuals and/or species. Thus, as recently proposed by Mel Greaves through paraphrasing Dobzhansky’s famous dictum, “nothing in cancer makes sense except in the light of evolution”.

This interdisciplinary field of research remains at the moment extremely promising, but it is still in its infancy, and fundamental studies (both theoretical and experimental) are still needed to pursue our understanding of the evolutionary ecology of tumors and of host–tumor interactions.

By assembling some of the latest, most exciting results, syntheses, and perspectives relating to the topic Ecology, Evolution and Cancer, our objective with this special issue is to reinforce the construction of a solid base for a balanced approach to cancer research, for oncologists and for ecologists.

Can Energetic Capacity Help Explain Why Physical Activity Reduces Cancer Risk?

Authors: Peter A. Biro; FrédéricThomas; Beata Ujvari; Christa Beckmann

Source: Trends in Cancer (June 2020)

Brief summary of the paper:

Physical activity substantially reduces the risk of developing cancer. As such, exercise promises to be a powerful preventative measure against cancer.

However, if we are to ‘prescribe’ exercise, we should identify how and why exercise affects cancer risk to provide informed prescriptions.

We find that high energetic capacity is both a cause and consequence of high sustained activity levels, both at a genetic level and due to training effects.

High energetic capacity in turn can increase immune responses and reduce incidence and progression of cancer, and this effect can be independent of activity. Thus, exercise may reduce cancer risk via increasing one’s energetic capacity for immune function.

In light of this potential mechanism, prescriptions for exercise might consider those likely to increase one’s energetic capacity, which may differ among individuals given innate differences in our ability to generate energy on a sustained basis.

Increased physical activity reduces cancer risk in humans, but why this whole-organism attribute reduces cancer remains unclear. Active individuals tend to have high capacity to generate energy on a sustained basis, which in turn can permit greater immune responses crucial for fighting emerging neoplasia.

Thus, we suggest energetic capacity as a potential mechanism to explain the activity–cancer link, given that humans are intrinsically (not externally) energy limited.

Human and rodent studies show that individuals with high energetic capacity mount greater immune responses and have lower cancer incidence; these trends persist after controlling for actual physical activity, supporting a direct role of energetic capacity.

If true, exercise efforts might best target those that increase one’s energetic capacity, which may be both individual and exercise specific.