RT Journal Article
SR Electronic
T1 From zygote to a multicellular soma: body size affects optimal growth strategies under cancer risk
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.16.877118
DO 10.1101/2019.12.16.877118
A1 E. Yagmur Erten
A1 Hanna Kokko
YR 2019
UL http://biorxiv.org/content/early/2019/12/16/2019.12.16.877118.abstract
AB 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.