Eco‐evolutionary perspectives of the dynamic relationships linking senescence and cancer

Authors: Jean‐François Lemaître, Samuel Pavard, Mathieu Giraudeau, Orsolya Vincze, Geordie Jennings, Rodrigo Hamede, Beata Ujvari & Frédéric Thomas


Brief summary of the paper: Evidence for actuarial senescence (i.e. the decrease in survival with increasing age) is now widespread across the tree of life. However, demographic senescence patterns are highly variable both between and within species. To understand these variations, there is an urgent need to go beyond aggregated mortality rates and to investigate how age‐specific causes of mortality in animals interact with age‐specific physiological performance. We address this question in the context of cancers.

Cancer is a leading cause of death in human populations and has recently been shown to be more prevalent across species than previously thought. Since anthropogenic perturbations drastically increase cancer rates in wild populations of animals, deciphering the complex interactions between senescence and cancer now constitutes a key challenge in evolutionary ecology.

Based on classical evolutionary theories of ageing, we first demonstrate that the occurrence of cancers might constitute an underestimated piece of the life‐history jigsaw. We propose that the selection for an increased allocation of resources towards growth and reproduction during early life might potentially favour cancer development, a life‐history pathway that might be functionally mediated by the process of immunosenescence. While we discuss the relevance of other proximate mechanisms suggesting that cancer arises as a direct consequence of senescence, we also argue that cancer itself can promote senescence by notably increasing the amount of resources required for somatic maintenance.

Contrary to theoretical predictions, recent empirical evidence suggests that senescence is an asynchronous process among physiological functions. At the same time, the timing of occurrence varies widely between the different types of cancers. We suggest that similar evolutionary forces might shape the synchronicity of senescence and cancer patterns, which emphasize the tight and complex relationships linking these processes.

We propose a conceptual background to lay down the foundations and the directions of future research projects aiming to disentangle the dynamic relationship between the evolution of cancer and senescence. We argue that studies embracing these research directions will markedly improve our understanding of both cancer prevalence and timing at the individual, population and species level.

Obesity paradox in cancer: Is bigger really better?

Authors: Beata Ujvari, Camille Jacqueline, Dorothée Misse, Valentin Amar, Jay C. Fitzpatrick, Geordie Jennings, Christa Beckmann, Sophie Rome, Peter A. Biro, Robert Gatenby, Joel Brown, Luis Almeida, Frédéric Thomas

Source: Evolutionary Applications, March 2019

Brief summary of the paper: While obesity is widely recognized as a risk factor for cancer, survival among patients with cancer is often higher for obese than for lean individuals. Several hypotheses have been proposed to explain this “obesity paradox,” but no consensus has yet emerged.

Here, we propose a novel hypothesis to add to this emerging debate which suggests that lean healthy persons present conditions unfavorable to malignant transformation, due to powerful natural defenses, whereby only rare but aggressive neoplasms can emerge and develop.

In contrast, obese persons present more favorable conditions for malignant transformation, because of several weight‐associated factors and less efficient natural defenses, leading to a larger quantity of neoplasms comprising both nonaggressive and aggressive ones to regularly emerge and progress.

If our hypothesis is correct, testing would require the consideration of the raw quantity, not the relative frequency, of aggressive cancers in obese patients compared with lean ones. We also discuss the possibility that in obese persons, nonaggressive malignancies may prevent the subsequent progression of aggressive cancers through negative competitive interactions between tumors.

Tracing the rise of malignant cell lines: Distribution, epidemiology and evolutionary interactions of two transmissible cancers in Tasmanian devils

Authors: Samantha James, Geordie Jennings, Young Mi Kwon, Maximilian Stammnitz, Alexandra Fraik, Andrew Storfer, Sebastien Comte, David Pemberton, Samantha Fox, Bill Brown, Ruth Pye, Gregory Woods, Bruce Lyons, Paul A. Hohenlohe, Hamish McCallum, Hannah Siddle, Frédéric Thomas, Beata Ujvari, Elizabeth P. Murchison, Menna Jones, Rodrigo Hamede

Source: Evolutionary Applications, June 2019

Brief summary of the paper: Emerging infectious diseases are rising globally and understanding host‐pathogen interactions during the initial stages of disease emergence is essential for assessing potential evolutionary dynamics and designing novel management strategies.

Tasmanian devils (Sarcophilus harrisii) are endangered due to a transmissible cancer—devil facial tumour disease (DFTD)—that since its emergence in the 1990s, has affected most populations throughout Tasmania. Recent studies suggest that devils are adapting to the DFTD epidemic and that disease‐induced extinction is unlikely.

However, in 2014, a second and independently evolved transmissible cancer—devil facial tumour 2 (DFT2)—was discovered at the d’Entrecasteaux peninsula, in south‐east Tasmania, suggesting that the species is prone to transmissible cancers.

To date, there is little information about the distribution, epidemiology and effects of DFT2 and its interaction with DFTD. Here, we use data from monitoring surveys and roadkills found within and adjacent to the d’Entrecasteaux peninsula to determine the distribution of both cancers and to compare their epidemiological patterns.

* Map of Tasmania and the d’Entrecasteaux peninsula in south eastern Tasmania showing the five study sites where standard live trapping was undertaken and the location of all diseased animals. The arrow indicates the first detected case of DFT2 in 2014.

Since 2012, a total of 51 DFTD tumours have been confirmed among 26 individuals inside the peninsula and its surroundings, while 40 DFT2 tumours have been confirmed among 23 individuals, and two individuals co‐infected with both tumours. All devils with DFT2 were found within the d’Entrecasteaux peninsula, suggesting that this new transmissible cancer is geographically confined to this area.

We found significant differences in tumour bodily location in DFTD and DFT2, with non‐facial tumours more commonly found in DFT2. There was a significant sex bias in DFT2, with most cases reported in males, suggesting that since DFT2 originated from a male host, females might be less susceptible to this cancer.

We discuss the implications of our results for understanding the epidemiological and evolutionary interactions of these two contemporary transmissible cancers and evaluating the effectiveness of potential management strategies.

Multiple paternity and precocial breeding in wild Tasmanian devils, Sarcophilus harrisii (Marsupialia: Dasyuridae)

Authors: Tracey Russell, Amanda Lane, Judy Clarke, Carolyn Hogg, Katrina Morris, Tamara Keeley, Thomas Madsen, Beata Ujvari

Source: Biological Journal of the Linnean Society, May 2019

Brief summary of the paper: Polyandry, a common reproductive strategy in various animal species, has potential female benefits, which include enhanced offspring fitness. Benefits can be direct, such as reduced risk of male infanticide of offspring, or indirect, such as increased genetic diversity of offspring and the acquisition of ‘good genes’. Multiple paternity of litters has been recorded in numerous marsupial species but has not been reported in Tasmanian devils, Sarcophilus harrisii (Boitard).

We investigated whether multiple paternity occurred in litters within a wild population of Tasmanian devils. Using major histocompatibility complex-linked and neutral microsatellite markers, the paternity of nine litters was analysed. We found multiple paternity in four out of nine litters and that yearling (> 1, < 2 years old) male devils were siring offspring. This is the first record of multiple paternity and of male precocial breeding in wild Tasmanian devils.

To date, there are no data relating to the subsequent survival of devils from single- vs. multiple-sired litters; therefore, we do not know whether multiple paternity increases offspring survival in the wild. These results have implications for the Tasmanian devil captive insurance programme, because group housing can lead to multiple-sired litters, making the maintenance of genetic diversity over time difficult to manage.

Transmissible cancer and the evolution of sex

Authors: Frédéric Thomas, Thomas Madsen, Mathieu Giraudeau, Dorothée Misse, Rodrigo Hamede, Orsolya Vincze, François Renaud, Benjamin Roche, Beata Ujvari

Source: Transmissible cancer and the evolution of sex. PLoS Biol 17(6), June 6, 2019

Brief summary of the paper: The origin and subsequent maintenance of sex and recombination are among the most elusive and controversial problems in evolutionary biology.

Here, we propose a novel hypothesis, suggesting that sexual reproduction not only evolved to reduce the negative effects of the accumulation of deleterious mutations and processes associated with pathogen and/or parasite resistance but also to prevent invasion by transmissible selfish neoplastic cheater cells, henceforth referred to as transmissible cancer cells.

Sexual reproduction permits systematic change of the multicellular organism’s genotype and hence an enhanced detection of transmissible cancer cells by immune system.

Given the omnipresence of oncogenic processes in multicellular organisms, together with the fact that transmissible cancer cells can have dramatic effects on their host fitness, our scenario suggests that the benefits of sex and concomitant recombination will be large and permanent, explaining why sexual reproduction is, despite its costs, the dominant mode of reproduction among eukaryotes.

Extreme Competence: Keystone Hosts of Infections

Authors: Lynn B. Martin, BriAnne Addison, Andrew G.D. Bean, Katherine L. Buchanan, Ondi L. Crino, Justin R. Eastwood, Andrew S. Flies, Rodrigo Hamede, Geoffrey E. Hill, Marcel Klaassen, Rebecca E. Koch, Johanne M. Martens, Constanza Napolitano, Edward J. Narayan, Lee Peacock, Alison J. Peel, Anne Peters, Nynke Raven, Alice Risely, Michael J. Roast, Lee A. Rollins, Manuel Ruiz-Aravena, Dan Selechnik, Helena S. Stokes, Beata Ujvari, Laura F. Grogan

Source: Trends in Ecology & Evolution, VOLUME 34, ISSUE 4, P303-314, APRIL 01, 2019

Brief summary of the paper: A few members of host populations, so-called superspreaders, have disproportionate impacts on the risk of infectious disease emergence and spread.
Several other forms of EC exist; some of which might be exceptionally protective.
To discover and understand forms of EC, it is imperative to describe the distribution of, and covariation among, traits of individual hosts that mediate the many stages of host–parasite interactions.

Here, we provide a framework to do so, emphasizing how interplay among host traits related to parasite exposure behavior, susceptibility, replicability of parasites on/in hosts, and transmissibility, comprise host competence.

We hope this framework helps reveal new forms of EC and informs and improves management of disease risk.

Individual hosts differ extensively in their competence for parasites, but traditional research has discounted this variation, partly because modeling such heterogeneity is difficult. This discounting has diminished as tools have improved and recognition has grown that some hosts, the extremely competent, can have exceptional impacts on disease dynamics. Most prominent among these hosts are the superspreaders, but other forms of extreme competence (EC) exist and others await discovery; each with potentially strong but distinct implications for disease emergence and spread. Here, we propose a framework for the study and discovery of EC, suitable for different host–parasite systems, which we hope enhances our understanding of how parasites circulate and evolve in host communities.

International Research Collaboration – What does it mean to us?

What do you reckon will be the outcome if you mix one book about the ecology and evolution of cancer, lots of  shared papers, one Dr Beata Ujvary, one Professor Fredric Thomas and a bit of funding from both the Australian Research Council and the French National Research Council ?

Well, the answer is simple – a very successful and productive international research collaboration that hopefully will allow us to better understand the mechanism of cancer.  This collaboration success was recognized earlier this year as Beata Ujvary and the team received the 2018 Vice Chancellor’s Award for International Research Collaboration.

Below: Beata and Fredric shed some light on their collaboration