Biology subjects

Agren, J. A.

Publications and source records attributed to Agren, J. A..

5 recordsLinked to original sources

bioRxiv2026

Internal evolutionary conflicts: a conceptual synthesis and mathematical primer

Internal evolutionary conflicts arise when elements within an organism have diverging fitness interests. Examples range from meiotic drive and cytoplasmic male sterility to transposable elements and supernumerary B chromosomes. While once treated as genetic curiosities, they are now seen as widespread and major drivers of eukaryotic genome evolution. Yet their study remains fragmented, with no clear entry point not only for those who wish to gain an overview of theoretical advances, or those who wish to construct models of their own. Here, we discuss ways in which internal evolutionary conflicts have been modelled and develop a common population genetic framework for building such models. The framework provides explicit criteria for what counts as conflict, distinguishing it from fitness trade-offs, and formalises how and when internal conflicts arise. By treating different cases within the same structure, it shows that these diverse phenomena share a common logic.

evolutionary biology↗

bioRxiv2024

Quantifying internal conflicts and their threats to organismal form and fitness

Evolutionary biologists often treat organisms as both fitness-maximizing agents and as the primary level at which adaptation manifests. Yet, genes and cells may also seek to optimize their fitness by distorting the Mendelian rules of transmission or by influencing organismal traits for their own benefit. Organismal form and fitness are therefore threatened from within by selfish genes and cells. However, to what extent such internal conflicts actually harm individual organisms and threaten our concept of the organism as the sole bearer of adaptation remains unclear. We introduce a mathematical framework to capture the threat posed by internal conflicts and develop two metrics to measure their various forms of harm. We name these metrics fitness unity and trait unity, and use them to refer to the threats posed by internal conflicts to an organisms role as the optimizing agent and the strategy wielded to achieve that optimization, respectively. We apply our framework to two examples of internal conflicts, genomic imprinting and sex ratio distortion, to illustrate how such harms from internal conflict may be quantified. We conclude by discussing the conditions under which internal conflict becomes sufficiently disruptive to organisms that it no longer makes sense to think of them as unified fitness-maximizing agents, but instead as adaptive compromises of multiple competing sub-agents.

evolutionary biology↗

bioRxiv2022

Spatial cumulant models enable spatially informed treatment strategies and analysis of local interactions in cancer systems

Theoretical and applied cancer studies that use individual-based models (IBMs) have been limited by the lack of a mathematical formulation that enables rigorous analysis of these models. However, spatial cumulant models (SCMs), which have arisen from theoretical ecology, describe population dynamics generated by a specific family of IBMs, namely spatio-temporal point processes (STPPs). SCMs are spatially resolved population models formulated by a system of differential equations that approximate the dynamics of two STPP-generated summary statistics: first-order spatial cumulants (densities), and second-order spatial cumulants (spatial covariances). We exemplify how SCMs can be used in mathematical oncology by modelling theoretical cancer cell populations comprising interacting growth factor-producing and non-producing cells. To formulate model equations, we use computational tools that enable the generation of STPPs, SCMs and mean-field population models (MFPMs) from user-defined model descriptions (Cornell et al., 2019). To calculate and compare STPP, SCM and MFPM-generated summary statistics, we develop an application-agnostic computational pipeline. Our results demonstrate that SCMs can capture STPP-generated population density dynamics, even when MFPMs fail to do so. From both MFPM and SCM equations, we derive treatment-induced death rates required to achieve non-growing cell populations. When testing these treatment strategies in STPP-generated cell populations, our results demonstrate that SCM-informed strategies outperform MFPM-informed strategies in terms of inhibiting population growths. We thus demonstrate that SCMs provide a new framework in which to study cell-cell interactions, and can be used to describe and perturb STPP-generated cell population dynamics. We, therefore, argue that SCMs can be used to increase IBMs applicability in cancer research. Statements and DeclarationsThe authors have no competing interests to declare that are relevant to the content of this article.

cancer biology↗

bioRxiv2019

Mitochondrial-Y chromosome epistasis in Drosophila melanogaster

The coordination between mitochondrial and nuclear genes is crucial to eukaryotic organisms. Predicting the nature of these epistatic interactions can be difficult because of the transmission asymmetry of the genes involved. While autosomes and X-linked genes are transmitted through both sexes, genes on the Y chromosome and in the mitochondrial genome are uniparentally transmitted through males and females respectively. Here, we generate 36 otherwise isogenic Drosophila melanogaster strains differing only in the geographical origin of their mitochondrial genome and Y chromosome to experimentally examine the effects of the uniparentally inherited parts of the genome, as well as their interaction, in males. We assay longevity and gene expression through RNA-sequencing. We detect an important role for both mitochondrial and Y-linked genes, as well as extensive mitochondrial-Y chromosome epistasis, in both traits. In particular, genes involved in male reproduction appear to be especially sensitive. Despite these interactions, we find no evidence that the mitochondrial genome and Y chromosome are co-adapted within a geographic region. Overall, our study demonstrates a key role for the uniparentally inherited parts of the genome for male biology, but also that mito-nuclear interactions are complex and not easily predicted from simple transmission asymmetries.

evolutionary biology↗

bioRxiv2018

Sexual Conflict through Mother’s Curse and Father’s Curse

In contrast with autosomes, lineages of sex chromosomes reside for different amounts of time in males and females, and this transmission asymmetry makes them hotspots for sexual conflict. Similarly, the maternal inheritance of the mitochondrial genome (mtDNA) means that mutations that are beneficial in females can spread in a population even if they are deleterious in males, a form of sexual conflict known as Mothers Curse. While both Mothers Curse and sex chromosome induced sexual conflict have been well studied on their own, the interaction between mitochondrial genes and genes on sex chromosomes is poorly understood. Here, we use analytical models and computer simulations to perform a comprehensive examination of how transmission asymmetries of nuclear, mitochondrial, and sex chromosome-linked genes may both cause and resolve sexual conflicts. For example, the accumulation of male-biased Mothers Curse mtDNA mutations will lead to selection in males for compensatory nuclear modifier loci that alleviate the effect. We show how the Y chromosome, being strictly paternally transmitted provides a particularly safe harbor for such modifiers. This analytical framework also allows us to discover a novel kind of sexual conflict, by which Y chromosome-autosome epistasis may result in the spread of male beneficial but female deleterious mutations in a population. We christen this phenomenon Fathers Curse. Extending this analytical framework to ZW sex chromosome systems, where males are the heterogametic sex, we also show how W-autosome epistasis can lead to a novel kind of nuclear Mothers Curse. Overall, this study provides a comprehensive framework to understand how genetic transmission asymmetries may both cause and resolve sexual conflicts.

evolutionary biology↗