Adaptive asexual evolution in cancer, corals and seagrasses - ADAPTASEX
Description: All multicellular organisms are genetic mosaics, composed of different cell populations that have acquired somatic mutations due to mitotic errors. It is generally assumed that this intra-organismal genetic heterogeneity is detrimental for organismal fitness and results in disease such as cancer and senescence. The goal of ADAPTASEX is to unite studies on the dark side of such genetic heterogeneity with an exploration of possible beneficial adaptive effects. In doing so, we are analyzing parallels in modular organisms that occur frequently among the plant and animal kingdom. Corals and seagrasses, as examples, grow asexually to very large size, resulting in clones (=genets) of hundreds of m2. Our research is motivated by preliminary, genetic marker based observations of within-genet heterogeneity (corals, seagrasses), its transfer to the germline, and the increasing recognition of the importance of genomic heterogeneity for predicting cancer etiology, dynamics and treatment. We will describe somatic genetic heterogeneity at the genome level of model coral and seagrass species, and compare patterns to available cancer data. For the free-living species, we perform experimentation to assess fitness effects of somatic genetic variants, and study the transfer of somatically generated variation to the sexual cycle. We hypothesize that the emergent multi-level selection contributes to adaptive dynamics and may purge deleterious genetic variation at the cell population level, explaining delayed senescence and reduced mutational load in modular species. Our interdisciplinary team will develop a joint modeling approach to follow adaptive dynamics of the observed intra-organismal genetic heterogeneity in diverse asexually evolving systems ranging from cancer to modular plant and animal genets and gain synergistic insights into the role of cell population competition and spatial structure for asexual selective sweeps. We will develop protocols to validate low frequency genetic variants, and to predict adaptive dynamics depending on localization, level of selection, and effects of somatic mutations. We expect to contribute to the unification of biological theory by establishing a framework for the study of somatically derived genetic variation from humans to plants, its evolutionary dynamics and fitness effects.
Funder: Human Frontier Science Program
Amount: $1,050,000
Funding type: award
Start date: 2020-12-01
End date: 2023-11-30
Investigator: Thorsten REUSCH
Institution: GEOMAR Helmholtz Centre for Ocean Research Kiel
Subfield: Cancer Research
Domain: Life Sciences
Funded outputs count: 1
Funder award ID: RGP0042/2020
OpenAlex ID: G476629178