Biology subjects

Casanova, A. G.

Publications and source records attributed to Casanova, A. G..

3 recordsLinked to original sources

bioRxiv2026

Coevolution of Codependent Hosts and Symbionts

Many endosymbioses in eukaryotes superficially appear to be beneficial to both participants. However, there is little direct evidence for this, and symbioses naturally set up conditions in which each member of the pair is under selection to extract resources from the other. Ultimately, the endosymbiont either evolves to be in conflict with the interests of the host or to act cooperatively with the host contrary to its own best interests. Focusing on obligate symbioses, we develop theory to clarify the population-genetic conditions favoring the alternative outcomes. The balance is usually tipped in favor of exploitation by the symbiont, particularly when the number of symbionts within host cells is high, selection is strong on symbionts relative to hosts, there is horizontal transfer of symbionts, and/or the symbionts have accelerated mutation rates or turnover times. If the symbiont conditions the host-cell biology to enhance within-host population sizes, selection for selfish symbionts will be further enhanced by the diminished level of within-host drift. Although the host evolves in parallel to exploit resources from the endosymbiont, the net result is often a stalemate in which the host is no better off than prior to host-symbiont coevolution. Strict vertical inheritance can result in an evolutionary alignment of interests of the endosymbiont and the host, as this minimizes the possibility of within-host selection, but even here there is a critical host population size below which the symbiont evolves to exploit the host. These results suggest that the evolutionary enslavement of a symbiont to benefit a host species requires a narrow mix of population-biological features of both participants.

evolutionary biology↗

bioRxiv2026

Fixation Probabilities of Mutant Alleles in an Ecological Context

For decades, population geneticists have relied upon a formula derived by Malecot and by Kimura to estimate the fixation probability of mutant alleles ({phi}). Among other things, this formula leads to the conclusion that in sufficiently large populations{phi} asymptotically approaches 2s(Ne/N ) (for small s), where s is the relative selective advantage of the mutant allele, and Ne and N respectively denote the effective and absolute (haploid) population sizes. In contrast, in sufficiently small populations,{phi} = 1/N, with the two domains of behavior being separated at the point where s [bsime] 1/(2Ne). These results hold when s, N, and Ne remain constant during the fixation process, but require modification when populations are changing in size. Here, we show that if there are ecological effects associated with competing alleles, such that the genetic composition of the population influences the total population size, the fixation probability of a beneficial allele can substantially deviate from the levels suggested above, even in the domain of effective neutrality (i.e., | s | [lsim]1/(2Ne)). We obtain analytical results for a variety of frequency-dependent functions for the overall population size, and show that the overall effect is largely a function of the response at low mutant-allele frequency. We also derive expressions for times to fixation and for fixation probabilities of deleterious alleles, and show how our results relate to prior work for the situation in which population sizes change in frequency-independent manners.

evolutionary biology↗

bioRxiv2023

Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis

Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cells dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis. While SMYD2 is overexpressed in aggressive breast cancers, we notice that it is not required for primary tumor growth. However, mammary-epithelium specific SMYD2 ablation increases mouse overall survival by blocking the primary tumor cells ability to metastasize. Mechanistically, we identify BCAR3 as a genuine physiological substrate of SMYD2 in breast cancer cells. BCAR3 monomethylated at lysine K334 (K334me1) is recognized by a novel methyl-binding domain present in FMNLs proteins. These actin cytoskeleton regulators are recruited at the cell edges by the SMYD2 methylation signaling and modulates lamellipodia properties. Breast cancer cells with impaired BCAR3 methylation loose migration and invasiveness capacity in vitro and are ineffective in promoting metastases in vivo. Remarkably, SMYD2 pharmacologic inhibition efficiently impairs the metastatic spread of breast cancer cells, PDX and aggressive mammary tumors from genetically engineered mice. This study provides a rationale for innovative therapeutic prevention of malignant breast cancer metastatic progression by targeting the SMYD2-BCAR3-FMNL axis.

cancer biology↗