Open research questions in Evolution and Genetic Dynamics
48 unresolved questions extracted from the limitations and future-work sections of 481 Evolution and Genetic Dynamics papers in our library. Each links back to the study that raised it.
What the literature leaves open
ABSTRACT The latitudinal diversity gradient (LDG) is observed across various biological groups, but its causes remain debated.
Despite recent comparisons of the DFE between populations and species, little is known about how this distribution changes over shorter evolutionary timescales.
We provide a reusable implementation and publicly release the source code to support reproducibility and facilitate further studies on robustness in dynamical GRN models.
A Reexamination of Noise-Driven Robustness Evolution in Gene Regulatory Networks · 2026This could be explored further by incorporating mutations with beneficial effects on 835 male fitness in our simulations, or considering models in which male mating success depends on a quantitative phenotypic trait whose optimal value may change over time. To our knowledge, the idea that sexual selection may be a source of negative epistasis among mutations has not been explored much theoretically and empirically. Indeed, while the exact timing of the different steps of meiosis has not been described yet in Hymenoptera (to our knowledge), in Drosophila meiosis is completed during the passage of oocytes through the oviduct, before fertilization (e.
Differential selection between sexes and the evolution of recombination in haplodiploids · 2026 · DOIBackground: Environmental conditions shape the evolutionary trajectories of RNA viruses, yet little is known about how complex physical stressors such as microgravity influence host-virus interactions and viral evolution.
Simulated microgravity alters short-term evolutionary trajectories of Orsay virus in Caenorhabdidits elegans · 2026 · DOIThe proof assumes specific equilibrium conditions (coexistence conditions like Coex2,3) hold, but the sensitivity analysis of how violations or perturbations to these conditions affect the emergence of dormancy is not addressed.
The proof relies on standard Freidlin–Wentzell type large-deviation arguments originating from prior work (Champagnat 2006; Coron et al. 2021), but the construction of coupling and adaptation to this specific multi-type model with viral lysis-induced death requires further detailed verification beyond what is presented.
Evolutionary repair experiments have identified molecular solutions to cellular defects in isolation, but predictive models that can anticipate which adaptive trajectories will be followed across different genetic backgrounds and initial perturbations remain absent.
Most experimental evolution studies of cell biology have operated under single-stress or laboratory conditions; the interaction between multiple simultaneous cellular stresses (DNA replication stress combined with microtubule depolymerization, metabolic constraints, thermal stress) during evolutionary adaptation has not been systematically investigated.
Gene loss has been shown to drive evolutionary adaptation in experimental evolution, but the systematic characterization of which specific cellular functions or protein domains tolerate loss versus require compensatory evolution across the full genome remains incomplete.
Experimental evolution studies have documented aneuploidy as an adaptive strategy in cell biology (e.g., yeast cytokinesis mutants, DNA replication stress adaptation), but the long-term stability and fitness costs of aneuploidy-driven solutions across extended evolution experiments beyond current timeframes are unknown.
While epistatic interactions and genetic interactions have been characterized in individual evolutionary repair experiments (e.g., reciprocal sign epistasis, diminishing returns epistasis), systematic mapping of epistatic architectures across multiple cellular pathways simultaneously during experimental evolution has not been conducted.
Experimental evolution studies of cell biology have primarily focused on unicellular organisms (yeast, bacteria, microalgae) and simple multicellular models (C. elegans, Drosophila); the applicability of evolutionary repair approaches to complex mammalian cell systems and tissue-level cellular processes remains unexplored.
The paper discusses polyploid giant cancer cells (PGCCs) and their depolyploidizing divisions generating paradiploid progeny, but does not specify experimental approaches needed to characterize the precise molecular regulation of depolyploidization, autophagic degradation rates, and factors determining progeny viability across different cancer cell lines.
While the paper references chromothripsis and chromoanasynthesis events in cancer and germline contexts, it lacks systematic comparative analysis of the molecular mechanisms triggering these catastrophic genome rearrangements across different cancer types, tissues, and therapeutic conditions to establish predictive biomarkers.
The paper identifies that oncologists should guide cancer treatment to avoid triggering macroevolutionary potentials in eukaryotic cells, but provides no concrete clinical protocols or therapeutic strategies for detecting or preventing activation of genome-transformative systems like chromothripsis, polyploidy, or chromoanasynthesis during chemotherapy or radiation therapy.
The contribution of women programmers to theoretical population biology research from the 1970s-1980s, identified by Dung et al. (2019) through acknowledgment analysis, requires systematic reconstruction of authorship credit under modern standards to establish accurate historical attribution and assess the magnitude of recognition disparity.
Variable environments facilitate maintenance of genetic diversity according to the Gillespie (1978) model revisited by Schreiber (2020), but the quantitative relationship between environmental variation parameters (magnitude, temporal autocorrelation, spatial heterogeneity) and polymorphism maintenance in multilocus systems has not been systematically mapped.
The bimodal size distribution of bacterial prophages explained by Khan and Wahl (2020) as resulting from multiple interacting forces requires validation through experimental manipulation of individual selective pressures to isolate their independent and interactive contributions to the observed distribution.
The FST measure of genetic distance and its mathematical properties, specifically its failure to satisfy the triangle inequality as observed by Sewall Wright (1979) and revisited by Arbisser and Rosenberg (2020), lacks a comprehensive characterization across different demographic scenarios, including varying population sizes, bottlenecks, and admixture patterns.
Neutral sampling theory has been extended to structured populations by Uyenoyama et al. (2020) building on Ewens (1972) and Karlin and McGregor (1972), but the application of this neutral framework to hierarchically structured populations with multiple levels of spatial organization and asymmetric migration rates remains underdeveloped.
The integration of evolutionary game theory with dynamical population-genetic models in frequency-dependent selection contexts remains incomplete for age-structured populations. Soares and Lessard (2020) address fixation probability in age-structured populations with public goods games, but the general extension of game-theoretic predictions across varying age structures and reproductive schedules has not been systematically characterized.
A unified theoretical framework reconciling the continuist/uniformitarian view of traditional evolutionary biologists with the discontinuist view of evolutionary developmental biologists requires explicit formalization of what constitutes 'discontinuity' at genetic versus phenotypic levels. The paper acknowledges this reconciliation is possible but does not provide the mathematical or conceptual models necessary to operationalize and test this unified framework.
Mutations in coding sequences of structural genes versus cis-regulatory sequences have not been systematically compared in their contribution to morphological evolution across different organisms and developmental systems. The paper notes that both types of mutations contribute to morphological change but lacks comparative quantitative analysis of their relative frequencies and phenotypic effects in multicellular organism evolution.
The temporal relationship between speciation events and subsequent changes in gene regulatory network organization across different taxa has not been systematically investigated. The paper hypothesizes that regulatory network divergence may occur after initial population divergence, but provides no framework for empirically testing whether gene regulatory network reorganization precedes, follows, or occurs independently of speciation in specific taxa.
Most-cited papers in Evolution and Genetic Dynamics
- Understanding Cultural Persistence and Change · The Review of Economic Studies · 2020 · 246 citations
- Shaping of microbial phenotypes by trade-offs · Nature Communications · 2024 · 97 citations
- How Individualized Niches Arise: Defining Mechanisms of Niche Construction, Niche Choice, and Niche Conformance · BioScience · 2022 · 80 citations
- Understanding the Genetic Basis of Variation in Meiotic Recombination: Past, Present, and Future · Molecular Biology and Evolution · 2024 · 72 citations
- The simplicity of protein sequence-function relationships · Nature Communications · 2024 · 49 citations
- <i>Caenorhabditis</i> nematodes colonize ephemeral resource patches in neotropical forests · Ecology and Evolution · 2022 · 41 citations
- Replaying germinal center evolution on a quantified affinity landscape · bioRxiv · 2026 · 27 citations
- Galton's Quincunx: Probabilistic causation in developmental behavior genetics · Studies in History and Philosophy of Science Part A · 2021 · 20 citations
- Statistical Inference for the Evolutionary History of Cancer Genomes · Statistical Science · 2020 · 20 citations
- A two-level model for the role of complex and young genes in the formation of organism complexity and new insights into the relationship between evolution and development · EvoDevo · 2018 · 18 citations
Most recent work
- Replaying germinal center evolution on a quantified affinity landscape · bioRxiv · 2026
- Sex-specific dominance and its effects on allelic diversity in sexually antagonistic loci · bioRxiv · 2026
- Inferring single-cell heterogeneity of bacteriophage lysis-associated life-history traits from population-scale dynamics · bioRxiv · 2026
- Loci under balancing selection facilitate the emergence of pseudo-overdominance and recombination suppression · bioRxiv · 2026
- Complex patterns of hitchhiking mutation load among stickleback populations · Genome Biology and Evolution · 2026
- Multilevel selection in multi-type populations · PNAS Nexus · 2026
- Darwinian fitness, its directional derivative, and Hamilton's rule for limited dispersal with class structure under within and between generation environmental stochasticity · bioRxiv · 2026
- Short- and long-term antagonistic selection explains dispersal polymorphism in the common lizard · Proceedings of the Royal Society B Biological Sciences · 2026
- Adaptation: by giant leaps or many tiny steps? · Nature Reviews Genetics · 2026
- A theoretical framework for how ecological interactions between microbes affect mutant fitness · bioRxiv · 2026
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