Does symmetry preclude the evolution of senescence? A comment on Pen and Flatt 2021

Funding Information: C.d.V. and H.K. were supported by Swiss National Science Foundation grant no. 310030B_182836. C.d.V. was also supported by an Academy of Finland grant (no. 340130, awarded to Jussi Lehtonen). E.Y.E. was supported by the National Institutes of Health (NIH) grant no. U54 CA217376 (awarded to Hanna Kokko) and Swiss National Science Foundation grant no. P500PB_203022.Peer reviewe

Diverse ways to think about cancer: What can we learn about cancer by studying it across the tree of life?

When asked about cancer, most would first think of it as a devastating disease. Some might add that lifestyle (e.g., smoking) or environmental pollution has something to do with it, but also that it tends to occur in old people. Cancer is indeed one of the most common causes of death in humans, and its incidence increases with age. Yet, focusing on our own species, we tend to overlook something very elementary: cancer is not unique to humans. In fact, it is a phenomenon that unifies diverse branches of the tree of life. Exploring the diversity of ways in which different organisms cope with it can lend us novel insights on cancer. In turn, by acknowledging cancer as a selective pressure, we can better understand the evolution of the biodiversity that surrounds us

From zygote to a multicellular soma: body size affects optimal growth strategies under cancer risk

Multicellularity evolved independently in multiple lineages, yielding organisms with a wide range of adult sizes. Building an intact soma is not a trivial task, when dividing cells accumulate damage. Here, we study ‘ontogenetic management strategies’, i.e. rules of dividing, differentiating and killing somatic cells, to examine two questions. First, do these rules evolve differently for organisms differing in the target mature body size, and second, how well a strategy evolved in small-bodied organisms performs if implemented in a large body – and vice versa (‘large’-evolved strategies in small bodies). We model the growth and mature lifespan of an organism starting from a single cell and optimize, using a genetic algorithm, trait combinations across a range of target sizes, with seven evolving traits: 1) probability of asymmetric division, 2) probability of differentiation (per symmetric cell division), 3) Hayflick limit, 4) damage response threshold, 5) damage response strength, 6) number of differentiation steps, 7) division propensity of cells relative to ‘stemness’. Some, but not all traits, evolve differently depending on body size: large-bodied organisms perform best with a smaller probability of differentiation, a larger number of differentiation steps on the way to form a tissue, and a higher threshold of cellular damage to trigger cell death, than small organisms. Strategies evolved in large organisms are more robust: they maintain high performance across a wide range of body sizes, while those that evolved in smaller organisms fail when attempting to create a large body. This highlights an asymmetry: under various risks of developmental failure and cancer, it is easier for a lineage to become miniaturized (should selection otherwise favour this) than to increase in size

Diverse ways to think about cancer : What can we learn about cancer by studying it across the tree of life?

When asked about cancer, most would first think of it as a devastating disease. Some might add that lifestyle (e.g., smoking) or environmental pollution has something to do with it, but also that it tends to occur in old people. Cancer is indeed one of the most common causes of death in humans, and its incidence increases with age. Yet, focusing on our own species, we tend to overlook something very elementary: cancer is not unique to humans. In fact, it is a phenomenon that unifies diverse branches of the tree of life. Exploring the diversity of ways in which different organisms cope with it can lend us novel insights on cancer. In turn, by acknowledging cancer as a selective pressure, we can better understand the evolution of the biodiversity that surrounds us

From zygote to a multicellular soma: Body size affects optimal growth strategies under cancer risk

Multicellularity evolved independently in multiple lineages, yielding organisms with a wide range of adult sizes. Building an intact soma is not a trivial task, when dividing cells accumulate damage. Here, we study ‘ontogenetic management strategies’, i.e. rules of dividing, differentiating and killing somatic cells, to examine two questions. First, do these rules evolve differently for organisms differing in the target mature body size, and second, how well a strategy evolved in small-bodied organisms performs if implemented in a large body – and vice versa (‘large’-evolved strategies in small bodies). We model the growth and mature lifespan of an organism starting from a single cell and optimize, using a genetic algorithm, trait combinations across a range of target sizes, with seven evolving traits: 1) probability of asymmetric division, 2) probability of differentiation (per symmetric cell division), 3) Hayflick limit, 4) damage response threshold, 5) damage response strength, 6) number of differentiation steps, 7) division propensity of cells relative to ‘stemness’. Some, but not all traits, evolve differently depending on body size: large-bodied organisms perform best with a smaller probability of differentiation, a larger number of differentiation steps on the way to form a tissue, and a higher threshold of cellular damage to trigger cell death, than small organisms. Strategies evolved in large organisms are more robust: they maintain high performance across a wide range of body sizes, while those that evolved in smaller organisms fail when attempting to create a large body. This highlights an asymmetry: under various risks of developmental failure and cancer, it is easier for a lineage to become miniaturized (should selection otherwise favour this) than to increase in size

Cancer risk and sexual conflict as constraints to body size evolution

Selection often favours large bodies, visible as Cope’s rule over macroevolutionary time — but size increases are not inevitable. One understudied cost of large bodies is the high number of cell divisions and the associated risk of oncogenic mutations. Our elasticity analysis shows that selection against a proportional increase in size becomes ever more intense with increasing body size if cancer is the sole selective agent. Thus cancer potentially halts body size increases even if no other constraint does so. We then provide multicellular realism with potentially sexually dimorphic body sizes and traits that control cell populations from zygote to maturity and beyond (ontogenetic management). This shows sexual conflict to extend to ontogeny; sexual dimorphism in mortalities and other life history measures may evolve even in the absence of any ecological causes underlying size- or sex-dependent mortality. Coadaptation of ontogenetic management and body size is required for substantial increases in size

Criticality and Information Dynamics in Epidemiological Models

Understanding epidemic dynamics has always been a challenge. As witnessed from the ongoing Zika or the seasonal Influenza epidemics, we still need to improve our analytical methods to better understand and control epidemics. While the emergence of complex sciences in the turn of the millennium have resulted in their implementation in modelling epidemics, there is still a need for improving our understanding of critical dynamics in epidemics. In this study, using agent-based modelling, we simulate a Susceptible-Infected-Susceptible (SIS) epidemic on a homogeneous network. We use transfer entropy and active information storage from information dynamics framework to characterise the critical transition in epidemiological models. Our study shows that both (bias-corrected) transfer entropy and active information storage maximise after the critical threshold ( R0 = 1). This is the first step toward an information dynamics approach to epidemics. Understanding the dynamics around the criticality in epidemiological models can provide us insights about emergent diseases and disease control

Transmissible cancers and the evolution of sex under the Red Queen hypothesis

The predominance of sexual reproduction in eukaryotes remains paradoxical in evolutionary theory. Of the hypotheses proposed to resolve this paradox, the ‘Red Queen hypothesis’ emphasises the potential of antagonistic interactions to cause fluctuating selection, which favours the evolution and maintenance of sex. Whereas empirical and theoretical developments have focused on host-parasite interactions, the premises of the Red Queen theory apply equally well to any type of antagonistic interactions. Recently, it has been suggested that early multicellular organisms with basic anticancer defences were presumably plagued by antagonistic interactions with transmissible cancers and that this could have played a pivotal role in the evolution of sex. Here, we dissect this argument using a population genetic model. One fundamental aspect distinguishing transmissible cancers from other parasites is the continual production of cancerous cell lines from hosts’ own tissues. We show that this influx dampens fluctuating selection and therefore makes the evolution of sex more difficult than in standard Red Queen models. Although coevolutionary cycling can remain sufficient to select for sex under some parameter regions of our model, we show that the size of those regions shrinks once we account for epidemiological constraints. Altogether, our results suggest that horizontal transmission of cancerous cells is unlikely to cause fluctuating selection favouring sexual reproduction. Nonetheless, we confirm that vertical transmission of cancerous cells can promote the evolution of sex through a separate mechanism, known as similarity selection, that does not depend on coevolutionary fluctuations

Bird size with dinosaur-level cancer defences: can evolutionary lags during miniaturisation explain cancer robustness in birds?

An increased appreciation of the ubiquity of cancer risk across the tree of life means we also need to understand the more robust cancer defences some species seem to have. Peto’s paradox, the finding that large-bodied species do not suffer from more cancer even if their lives require far more cell divisions than those of small species, can be explained if large size selects for better cancer defences. Since birds live longer than non-flying mammals of an equivalent body size, and birds are descendants of moderate-sized dinosaurs, we ask whether ancestral cancer defence innovations are retained if body size shrinks in an evolutionary lineage. Our model derives selection coefficients and fixation events for gains and losses of cancer defence innovations over macroevolutionary time, based on known relationships between body size, intrinsic cancer risk, extrinsic mortality (modulated by flight ability) and effective population size. We show that evolutionary lags can, under certain assumptions, explain why birds, descendants of relatively large bodied dinosaurs, retain low cancer risk. Counterintuitively, it is possible for a bird to be ‘too robust’ for its own good: excessive cancer suppression can take away from reproductive success. On the other hand, an evolutionary history of good cancer defences may also enable birds to reap the lifespan-increasing benefits of other innovations such as flight