Authors: Emy Beaumont, Jacques Brodeur, Frédéric Thomas, Antoine M. Dujon, Sonia Lupien

Source: Psychoneuroendocrinology (Feb 2024)

Abstract

Background: Schizophrenia is a mental illness that affects approximately 24 million people worldwide. Vulnerability to schizophrenia has been linked by some epidemiologic studies to Toxoplasma gondii (TG), an intracellular protozoan parasite that can form permanent cysts in the brain. Knowing that stress can increase the permeability of the blood-brain barrier, we hypothesized that stress could facilitate brain infection by TG, thus promoting the development of schizophrenia symptoms. The objective of this study was to test if different types of stress: acute stress (salivary cortisol), chronic stress (hair cortisol), or childhood adversity (Childhood Experiences of Violence Questionnaire), modulate the link between TG (TG antibodies in serum) and schizophrenia.

Method: Data and biospecimens (saliva, hair and serum) from 226 schizophrenic patients and 129 controls from the Signature Bank of the Centre de recherche de l’Institut Universitaire en Santé Mentale de Montréal were analysed. Hypothesis was tested using logistic regressions. Sex and age were included as covariates.

Results: Interaction effects revealed that the relation between TG seropositivity and the risk of developing schizophrenia was modulated by levels of hair cortisol (chronic stress; OR = 3.97, CI₉₅ = 1.01- 15.71, p=.049). However, salivary cortisol (acute stress; OR = 1.72, CI₉₅ = 0.60-4.95, p=.315) and childhood adversity (OR = 1.01, CI₉₅ = 0.85-1.19, p=.931) did not increase the risk of schizophrenia in TG infected patients.

Conclusion: These results provide a step towards a better understanding of the role of stress in the association between TG and schizophrenia.

Authors: Antoine M. Dujon, Justine Boutry, Sophie Tissot, Jordan Meliani, Anna Miltiadous, Jácint Tokolyi, Beata Ujvari, Frédéric Thomas

Source: Science of The Total Environment (Aug 2024)

Abstract

Tumoural processes, ubiquitous phenomena in multicellular organisms, influence evolutionary trajectories of all species. To gain a holistic understanding of their impact on species’ biology, suitable laboratory models are required. Such models are characterised by a widespread availability, ease of cultivation, and reproducible tumour induction. It is especially important to explore, through experimental approaches, how tumoural processes alter ecosystem functioning.

The cnidarian Hydra oligactis is currently emerging as a promising model due to its development of both transmissible and non-transmissible tumours and the wide breadth of experiments that can be conducted with this species (at the individual, population, mechanistic, and evolutionary levels). However, tumoural hydras are, so far, only documented in Europe, and it is not clear if the phenomenon is local or widespread.

In this study we demonstrate that Australian hydras from two independent river networks develop tumours in the laboratory consisting of interstitial stem cells and display phenotypic alterations (supernumerary tentacles) akin to European counterparts. This finding confirms the value of this model for ecological and evolutionary research on host-tumour interactions.

Authors: Mathieu Giraudeau, Orsolya Vincze, Sophie M. Dupont, Tuul Sepp, Ciara Baines, Jean-Francois Lemaitre, Karin Lemberger, Sophie Gentès, Amy Boddy, Antoine M. Dujon, Georgina Bramwell, Valerie Harris, Beata Ujvari, Catherine Alix-Panabières, Stephane Lair, David Sayag, Dalia A. Conde, Fernando Colchero, Tara M. Harrison, Samuel Pavard, Benjamin Padilla-Morales, Damien Chevallier, Rodrigo Hamede, Benjamin Roche, Tamas Malkocs, Athena C. Aktipis, Carlo Maley, James DeGregori, Guillaume Le Loc’h, Frédéric Thomas

Source: Journal of Animal Ecology (Aug 2024)

Abstract

The last few years have seen a surge of interest from field ecologists and evolutionary biologists to study neoplasia and cancer in wildlife. This contributes to the One Health Approach, which investigates health issues at the intersection of people, wild and domestic animals, together with their changing environments. Nonetheless, the emerging field of wildlife cancer is currently constrained by methodological limitations in detecting cancer using non-invasive sampling. In addition, the suspected differential susceptibility and resistance of species to cancer often make the choice of a unique model species difficult for field biologists.

Here, we provide an overview of the importance of pursuing the study of cancer in non-model organisms and we review the currently available methods to detect, measure and quantify cancer in the wild, as well as the methodological limitations to be overcome to develop novel approaches inspired by diagnostic techniques used in human medicine.

The methodology we propose here will help understand and hopefully fight this major disease by generating general knowledge about cancer, variation in its rates, tumour-suppressor mechanisms across species as well as its link to life history and physiological characters. Moreover, this is expected to provide key information about cancer in wildlife, which is a top priority due to the accelerated anthropogenic change in the past decades that might favour cancer progression in wild populations.

Authors: Antoine M Dujon, Beata Ujvari, Sophie Tissot, Jordan Meliani, Océane Rieu, Nikita Stepanskyy, Rodrigo Hamede, Jácint Tokolyi, Aurora Nedelcu, Frédéric Thomas

Source: Evolutionary Applications (Aug 2024)

Abstract

Growing evidence indicates that human activities are causing cancer rates to rise in both human and wildlife populations. This is due to the inability of ancestral anti-cancer defences to cope with modern environmental risks. The evolutionary mismatch between modern oncogenic risks and evolved cancer defences has far-reaching effects on various biological aspects at different timeframes, demanding a comprehensive study of the biology and evolutionary ecology of the affected species.

Firstly, the increased activation of anti-cancer defences leads to excessive energy expenditure, affecting other biological functions and potentially causing health issues like autoimmune diseases. Secondly, tumorigenesis itself can impact important fitness-related parameters such as competitiveness, predator evasion, resistance to parasites, and dispersal capacity. Thirdly, rising cancer risks can influence the species’ life-history traits, often favoring early reproduction to offset fitness costs associated with cancer.

However, this strategy has its limits, and it may not ensure the sustainability of the species if cancer risks continue to rise. Lastly, some species may evolve additional anti-cancer defences, with uncertain consequences for their biology and future evolutionary path.

In summary, we argue that the effects of increased exposure to cancer-causing substances on wildlife are complex, ranging from immediate responses to long-term evolutionary changes. Understanding these processes, especially in the context of conservation biology, is urgently needed.

Authors: Nick MacDonald, Nynke Raven, Wendy Diep, Samantha Evans, Senuri Pannipitiya, Georgina Bramwell, Caitlin Vanbeek, Frédéric Thomas, Tracey Russell, Antoine M. Dujon, Marina Telonis-Scott & Beáta Újvári

Source: Scientific Reports (May 2024)

Abstract

Cancer is a disease that many multicellular organisms have faced for millions of years, and species have evolved various tumour suppression mechanisms to control oncogenesis. Although cancer occurs across the tree of life, cancer related mortality risks vary across mammalian orders, with Carnivorans particularly affected.

Evolutionary theory predicts different selection pressures on genes associated with cancer progression and suppression, including oncogenes, tumour suppressor genes and immune genes. Therefore, we investigated the evolutionary history of cancer associated gene sequences across 384 mammalian taxa, to detect signatures of selection across categories of oncogenes (GRB2, FGL2 and CDC42), tumour suppressors (LITAF, Casp8 and BRCA2) and immune genes (IL2, CD274 and B2M).

This approach allowed us to conduct a fine scale analysis of gene wide and site-specific signatures of selection across mammalian lineages under the lens of cancer susceptibility. Phylogenetic analyses revealed that for most species the evolution of cancer associated genes follows the species’ evolution.

The gene wide selection analyses revealed oncogenes being the most conserved, tumour suppressor and immune genes having similar amounts of episodic diversifying selection. Despite BRCA2’s status as a key caretaker gene, episodic diversifying selection was detected across mammals. The site-specific selection analyses revealed that the two apoptosis associated domains of the Casp8 gene of bats (Chiroptera) are under opposing forces of selection (positive and negative respectively), highlighting the importance of site-specific selection analyses to understand the evolution of highly complex gene families.

Our results highlighted the need to critically assess different types of selection pressure on cancer associated genes when investigating evolutionary adaptations to cancer across the tree of life. This study provides an extensive assessment of cancer associated genes in mammals with highly representative, and substantially large sample size for a comparative genomic analysis in the field and identifies various avenues for future research into the mechanisms of cancer resistance and susceptibility in mammals.

Authors: Georgina Bramwell, James DeGregori, Frédéric Thomas, Beáta Újvári

Source: Evolution (Apr 2024)

Abstract

Evolutionary theory predicts that the accumulation of deleterious mutations in asexually reproducing organisms should lead to genomic decay. Clonally reproducing cell lines, i.e., transmissible cancers, when cells are transmitted as allografts/xenografts, break these rules and survive for centuries and millennia.

The currently known 11 transmissible cancer lineages occur in dogs (canine venereal tumour disease), in Tasmanian devils (devil facial tumor diseases, DFT₁ and DFT₂), and in bivalves (bivalve transmissible neoplasia). Despite the mutation loads of these cell lines being much higher than observed in human cancers, they have not been eliminated in space and time.

Here, we provide potential explanations for how these fascinating cell lines may have overcome the fitness decline due to the progressive accumulation of deleterious mutations and propose that the high mutation load may carry an indirect positive fitness outcome.

We offer ideas on how these host–pathogen systems could be used to answer outstanding questions in evolutionary biology. The recent studies on the evolution of these clonal pathogens reveal key mechanistic insight into transmissible cancer genomes, information that is essential for future studies investigating how these contagious cancer cell lines can repeatedly evade immune recognition, evolve, and survive in the landscape of highly diverse hosts.

Authors: Frédéric Thomas, Beáta Újvári, Antoine M Dujon

Source: Medecine sciences (Article in French) (Apr 2024)

Abstract

Cancer is an inevitable collateral problem inherent in the evolution of multicellular organisms, which appeared at the end of the Precambrian. Faced to this constraint, a range of diverse anticancer defenses has evolved across the animal kingdom. Today, investigating how animal organisms, especially those of large size and long lifespan, manage cancer-related issues has both fundamental and applied outcomes, as it could inspire strategies for preventing or treating human cancers.

In this article, we begin by presenting the conceptual framework for understanding evolutionary theories regarding the development of anti-cancer defenses. We then present a number of examples that have been extensively studied in recent years, including naked mole rats, elephants, whales, placozoa, xenarthras (such as sloths, armadillos and anteaters) and bats.

The contributions of comparative genomics to understanding evolutionary convergences are also discussed. Finally, we emphasize that natural selection has also favored anti-cancer adaptations aimed at avoiding mutagenic environments, for example by maximizing immediate reproductive efforts in the event of cancer. Exploring these adaptive solutions holds promise for identifying novel approaches to improve human health.

Authors: Grace Day, Kate Robb, Andrew Oxley, Marina Telonis-Scott, Beáta Újvári

Source: iScience (Apr 2024)

Abstract

A quarter of marine mammals are at risk of extinction, with disease and poor habitat quality contributing to population decline. Investigation of the Major Histocompatibility Complex (MHC) provides insight into species’ capacity to respond to immune and environmental challenges.

The eighteen available cetacean chromosome level genomes were used to annotate MHC Class I loci, and to reconstruct the phylogenetic relationship of the described loci. The highest number of loci was observed in the striped dolphin (Stenella coeruleoalba), while the least was observed in the pygmy sperm whale (Kogia breviceps) and rough toothed dolphin (Steno bredanensis).

Of the species studied, Mysticetes had the most pseudogenes. Evolutionarily, MHC Class I diverged before the speciation of cetaceans. Yet, locus one was genomically and phylogenetically similar in many species, persisting over evolutionary time. This characterisation of MHC Class I in cetaceans lays the groundwork for future population genetics and MHC expression studies.

Authors: Gábor Valcz, Edit I Buzás, Robert A Gatenby, Beáta Újvári, Béla Molnár

Source: Biochimica et Biophysica Acta (BBA) – Reviews on Cancer (Mar 2024)

Abstract

Although conventional anti-cancer therapies remove most cells of the tumor mass, small surviving populations may evolve adaptive resistance strategies, which lead to treatment failure. The size of the resistant population initially may not reach the threshold of clinical detection (designated as measurable residual disease/MRD) thus, its investigation requires highly sensitive and specific methods.

Here, we discuss that the specific molecular fingerprint of tumor-derived small extracellular vesicles (sEVs) is suitable for longitudinal monitoring of MRD. Furthermore, we present a concept that exploiting the multiparametric nature of sEVs may help early detection of recurrence and the design of dynamic, evolution-adjusted treatments.

Authors: Anna Miltiadous, Damien L. Callahan, Antoine M. Dujon, Katherine L. Buchanan, Lee A. Rollins

Source: Molecular Ecology (Jan 2024)

Abstract

Avian embryos develop in an egg composition which reflects both maternal condition and the recent environment of their mother. In birds, yolk corticosterone (CORT) influences development by impacting pre- and postnatal growth, as well as nestling stress responses and development. One possible mechanism through which maternal CORT may affect offspring development is via changes to offspring DNA methylation.

We sought to investigate this, for the first time in birds, by quantifying the impact of manipulations to maternal CORT on offspring DNA methylation. We non-invasively manipulated plasma CORT concentrations of egg-laying female zebra finches (Taeniopygia castanotis) with an acute dose of CORT administered around the time of ovulation and collected their eggs.

We then assessed DNA methylation in the resulting embryonic tissue and in their associated vitelline membrane blood vessels, during early development (5 days after lay), using two established methods – liquid chromatography–mass spectrometry (LC–MS) and methylation-sensitive amplification fragment length polymorphism (MS-AFLP). LC–MS analysis showed that global DNA methylation was lower in embryos from CORT-treated mothers, compared to control embryos. In contrast, blood vessel DNA from eggs from CORT-treated mothers showed global methylation increases, compared to control samples. There was a higher proportion of global DNA methylation in the embryonic DNA of second clutches, compared to first clutches. Locus-specific analyses using MS-AFLP did not reveal a treatment effect.

Our results indicate that an acute elevation of maternal CORT around ovulation impacts DNA methylation patterns in their offspring. This could provide a mechanistic understanding of how a mother’s experience can affect her offspring’s phenotype.