Authors: Frédéric Thomas, Antoine M. Dujon, Daniel Vaiman, Gerard Eberl, Catherine Alix-Panabières, Pascal Pujol, Beata Ujvari, Jordan Meliani, Aurora M. Nedelcu, Jean-Pascal Capp

Source: Evolutionary Applications (Feb 2026)

Abstract

Pathological processes are often conceptualized as localized phenomena anchored in a primary tumor, a focal lesion, or a single organ. However, growing evidence indicates that many diseases persist and progress as complex distributed systems, maintained by interactions among multiple sites. Building on the emerging framework of selection for function, which can be applied to understand the evolutionary persistence of both replicating and non-replicating entities, we propose that metastases, amyloidoses, fibroses, autoimmune syndromes, granulomatous diseases, and multifocal reproductive disorders can all be understood as complex evolving pathological systems within individuals.

In these contexts, local units such as metastatic nodules, amyloid plaques, or fibrotic foci act as semi-autonomous entities, yet achieve collective persistence through systemic flows, feedback loops, and network-level interactions, where local structuration gives rise to systemic effects. At certain points, lesions that produce mediators can trigger systemic alterations that, in turn, favor the emergence and persistence of additional lesions.

This creates a vicious cycle in which local and systemic dynamics reinforce one another, helping these specific pathological networks to overcome host defense mechanisms and persist (i.e., be ‘selected’ via differential persistence). This perspective unifies seemingly disparate conditions under the principle of system persistence, reframing pathology as an emergent organizational property of a pathological system rather than as isolated local breakdowns of organismal components. It also carries important implications for evolutionary medicine, suggesting a taxonomy of diseases that distinguishes localized from distributed functional pathologies. Clinically, it underscores the need to go beyond focal interventions, advocating instead for therapies that disrupt pathological connectivity, destabilize network coherence, and monitor systemic biomarkers of disease persistence.

Recognizing the role of selection for function in the emergence and persistence of complex pathological systems opens new avenues for both theoretical integration and therapeutic innovation in evolutionary medicine.

Authors: Anne-Lise Gérard, Florence Pirard, Caitlin Vanbeek, Antoine M. Dujon, Aaron G. Schultz, Rodrigo K. Hamede, Hannah V. Siddle, Frédéric Thomas, Matthew McKenzie, Mark D. Ziemann, Beata Ujvari

Source: The Febs Journal (Jan 2026)

Abstract

Devil Facial Tumour Diseases (DFTD), threatening Tasmanian devils, consist of two distinct transmissible cancers, DFT1 and DFT2, with differing origins and geographic spread. We investigated the metabolic differences between DFT1 and DFT2, examining cell viability, metabolic outputs, and bulk gene expression.

Using both DFT1 and DFT2 cell lines and biopsies, we found that glycolysis, oxidative phosphorylation, glutamate metabolism, and fatty acid synthesis are all essential for the survival of both tumour types. However, DFT2 exhibited higher rates of glycolysis and lactate generation compared to DFT1.

This coincided with elevated ATP production, cholesterol biosynthesis, and ROS generation, as well as an increased reliance on fatty acid metabolism. Furthermore, DFT2 is less metabolically adaptable than DFT1, being unable to switch to oxidative phosphorylation as DFT1 can when required. These metabolic changes in DFT2, in conjunction with its higher growth rate, suggest a more aggressive cancer phenotype than DFT1.

Our findings highlight distinct metabolic adaptations in DFT2 that may contribute to its competitive advantage.

Authors: Luca Luiselli, Thomas Madsen

Source: African Journal Of Ecology (Jan 2026)

Abstract

The ongoing biodiversity crisis is driven primarily by habitat degradation and accelerating climate change, with extreme climatic events increasingly shaping population dynamics across taxa. Detecting and interpreting these effects requires long-term ecological studies, yet such datasets remain rare, including Africa where biodiversity is high and ecological systems are strongly influenced by climatic variability and human land use.

Here we synthesise evidence demonstrating why short- and even medium-term studies often fail to capture the demographic consequences of climate change, especially those driven by rare but severe events such as droughts and floods. Drawing on case studies from temperate and tropical systems—including predator–prey collapses, reptile population crashes and iconic long-term projects such as Gombe and Amboseli—we show how sustained monitoring has transformed ecological understanding and conservation priorities.

We emphasise that Africa’s ecological complexity and prevalence of long-lived species make long-term, population-focused research particularly critical. However, funding structures and institutional constraints frequently undermine continuity. To address this gap, we propose an integrative framework combining targeted long-term ecological research funding, institutional support for data continuity, community-based monitoring and local ecological knowledge, and the integration of diverse data sources.

We argue that long-term monitoring is not a luxury but a scientific and ethical necessity for effective conservation under rapid environmental change.

Authors: Nikita Stepanskyy; Jordan Meliani; Jácint Tökölyi; Aurora M. Nedelcu; Pascal Pujol; Beata Ujvari; Frédéric Thomas; Antoine M. Dujon

Source: Proceedings Of The Royal Society B-biological Sciences (Aug 2026)

Abstract

Reproduction is a key life-history trait but often comes at the expense of somatic maintenance, including ageing and susceptibility to disease. While reproduction–immunity trade-offs have been experimentally demonstrated in the context of infectious diseases, whether reproduction similarly undermines susceptibility to tumours has remained unclear.

Using the freshwater cnidarian Hydra oligactis, in which tumours arise spontaneously and reproductive effort can be experimentally modulated through food availability, we tested the possibility of a trade-off between reproduction and tumour dynamics. Higher reproductive effort increased the likelihood of tumour development, reduced the probability of remission and increased the likelihood of progression to advanced stages. Resource availability modulated the strength of the trade-off in terms of tumour risk and remission, whereas tumour severity was determined solely by reproductive effort.

Together, these findings provide rare empirical support for a trade-off between reproduction and tumour dynamics, demonstrating that reproductive investment compromises both tumour prevention and control and that its expression can be shaped by environmental conditions. More broadly, they suggest that cancer susceptibility in more complex lineages may instead reflect evolutionary trade-offs that prioritize reproduction over somatic maintenance, helping illustrate one mechanism by which evolutionary trade-offs contribute to the persistence of cancer and to variation in susceptibility across taxa.

Authors: Beichen Yang, Matthew K. Jago, Thomas S. Mock, Barney M. Hines, Michael J. Salini, Giovanni M. Turchini, Richard P. Smullen, Nynke Raven, David S. Francis

Source: Aquaculture (Dec 2025)

Abstract

Dietary choline plays a functional role in lipid metabolism of Atlantic salmon. Fillet and visceral adipose tissue have been considered as the primary sites for lipid and energy storage. Currently, the effects of dietary choline inclusion on lipid metabolism, particularly triacylglycerol storage and metabolism in visceral adipose tissue of Atlantic salmon, remain poorly understood. To test this, four diets were formulated and manufactured with graded levels of choline (2.5, 3.3, 4.4, and 5.2 mg/g diet) and fed to juvenile Atlantic salmon for 124 days.

This study showed that the impact of dietary choline concentration on lipid deposition was primarily reflected in the visceral adipose tissue instead of the fillet. In visceral adipose tissue, both triacylglycerol and phosphatidylcholine concentration responded quadratically as dietary choline concentration increased (P < 0.05), however, these two lipid classes were negatively correlated (P < 0.05). Regression revealed that both the highest (5.2 mg/g) and lowest levels of dietary choline (2.5 mg/g) accumulated higher triacylglycerol associated with adipocyte hypertrophy in visceral adipose tissue relative to moderate inclusion levels.

The highest level of dietary choline tested (5.2 mg/g) demonstrated enhanced diacylglycerol acyltransferase-dependent triacylglycerol synthesis, however, this was accompanied by the lowest protein, energy and dry matter digestibility. The inclusion level of 2.5 mg/g dietary choline was considered deficient for Atlantic salmon, given the prevalence of visceral adiposity and growth retardation, accompanied by the lowest apparent choline digestibility.

This study highlights the impact of dietary choline levels on triacylglycerol storage and metabolism in the visceral adipose tissue of Atlantic salmon.

Authors: Antoine M. Dujon, Jonas Courtalon, Anna Miltiadous, Maci Blake, Beata Ujvari, Peter A. Biro, Frédéric Thomas

Source: Iscience (Nov 2025)

Abstract

Oncogenic pressures, factors that increase tumor risk, are intensifying with human-driven environmental change, yet their ecological effects remain mainly unquantified.

We examined how UVB-induced oncogenic stress affects interactions between two Australian freshwater planaria: the globally invasive predator Girardia tigrina and the native prey Cura pinguis. We hypothesized that DNA damage could either heighten prey vulnerability or impair predator performance.

Native planaria showed less UVB-induced DNA damage, likely due to darker pigmentation, while damage in G. tigrina reduced predation rates, suggesting energetic costs of DNA repair. UVB also reduced movement in both species, with partial recovery in the invasive species but prolonged immobility in the native. Additionally, UVB strongly suppressed asexual reproduction in G. tigrina, indicating trade-offs between DNA repair and proliferation.

These results reveal that oncogenic stress can reshape species interactions and invasion dynamics, underscoring the need to integrate cancer ecology into conservation and invasion biology.

Authors: Frédéric Thomas, Antoine M. Dujon

Source: BioEssays (Dec 2025)

Abstract

Laplane et al. recently provided a valuable framework for understanding cancer evolution through multilevel selection (MLS), distinguishing between MLS1, where groups differ in persistence based on the traits of their constituent cells but do not reproduce or evolve group-level adaptations, and MLS2, where groups themselves reproduce and possess emergent fitness distinct from that of individual cells. However, as the authors themselves acknowledge, applying MLS2 to metastasis is challenging for several reasons.

We argue that, rather than behaving as isolated evolutionary units, tumor sites function as components of a distributed system. This perspective suggests that metastasis may be better understood through the lens of selection for function, a framework that explains how traits contributing to system-level persistence can be maintained without requiring group-level reproduction.

This approach complements MLS theory and helps account for the resilience of the metastatic system as a whole, namely, the persistence and coordination of multiple tumor sites functioning as a collective rather than as isolated tumors, beyond classical Darwinian models.

It also aligns with the view that metastasis may reflect the reactivation of ancient cellular programs in a novel, nonreproductive context.

Authors: Orsolya Vincze, Piotr Minias, Alexandre Corthay, Fernando Colchero, Jean-François Lemaître, Louise Maille, Tamás Malkócs, Justus Hagemann, Dalia A. Conde, Samuel Pavard, Antoine M. Dujon, Beata Ujvari, Frédéric Thomas, Amy M. Boddy, Carlo C. Maley, Damien Chevallier, Tuul Sepp, Thomas Pradeu & Mathieu Giraudeau

Source: Nature Communications (Nov 2025)

Abstract

Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be.

The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance.

Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation.

Our results show that the expansion of the MHC class I gene complex, as well as increased selection for diversity at these genes is associated with sharply decreasing cancer mortality risk across mammals.This suggests that the efficient presentation of diverse peptides in somatic cells is important for cancer suppression across mammals, providing pioneering evidence that supports the cancer immunosurveillance hypothesis across species.

Authors: Emily Hann, Debolina Majumdar, Daniel Layton, Mohamed Fareh, David M Cahill, Mark Ziemann, Beata Ujvari, Karel A Schat, Arjun Challagulla

Source: Functional & Integrative Genomics (Nov 2025)

Abstract

The CRISPR-Cas13 system has emerged as a powerful platform for programmable RNA targeting, offering efficient and sequence-specific silencing of coding and non-coding transcripts. The RNA-targeting capabilities of CRISPR-Cas13 have been harnessed to silence transcripts harbouring pathogenic mutations and combat infectious diseases. However, the molecular basis of on-target and collateral activity are not completely understood, limiting the utility of Cas13 systems.

In this study, we delineate the principles for the development of effective crRNAs by targeting DsRed fluorescence reporter and synthetic influenza mRNA in chicken fibroblast DF1 cells. To systematically determine the optimal design for RfxCas13d crRNA, we investigated the minimum length of the crRNA, importance of protospacer flanking sequence, degree of mismatch tolerance, and off target effects.

Our data reveal variable knockdown levels between crRNAs, in which several crRNAs achieved over 95% target knockdown. We show that crRNAs exhibit a high degree of tolerance to single-nucleotide mismatches, regardless of their position in the spacer sequence. However, 4-nt mismatches between the spacer and the target significantly reduces targeting efficacy, whereas eight nucleotide mismatches completely abolish the activity of RfxCas13d. Finally, we compared targeting efficiency and collateral activity of two widely used RfxCas13d and HfCas13d variants.

Our data extend current understanding of Cas13d-mediated RNA targeting and offer a framework for rational crRNA design to enhance effectiveness in diverse applications, including antiviral strategies.

Authors: Frédéric Thomas, Jean-Pascal Capp, Antoine M Dujon, Andriy Marusyk, Klara Asselin, Mario Campone, Pascal Pujol, Catherine Alix-Panabières, Benjamin Roche, Beata Ujvari, Robert Gatenby, Aurora M Nedelcu

Source: Evolution Medicine And Public Health (Aug 2025)

Abstract

Current cancer therapies often fail due to tumor heterogeneity and rapid resistance evolution. A new evolutionary framework, ‘selection for function,’ proposes that tumor progression is driven by group phenotypic composition (GPC) and its interaction with the microenvironment, not by individual cell traits.

This perspective opens new therapeutic avenues: targeting the tumor’s functional networks rather than individual cells. Real-time tracking of GPC changes could inform adaptive treatments, delaying progression and resistance. By integrating evolutionary and ecological principles with conventional therapies, this strategy aims to transform cancer from a fatal to a manageable chronic disease.

Crucially, it does not necessarily require new drugs but offers a way to repurpose existing therapies to impair a tumor’s evolutionary potential. By steering tumor evolution toward less aggressive states, this approach could improve prognosis and long-term patient survival compared to current methods.We argue that leveraging GPC dynamics represents a critical, yet underexplored, opportunity in oncology.