Beyond Standardization: Improving External Validity and Reproducibility in Experimental Evolution

Desjardins, Eric; Kurtz, Joachim; Kranke, Nina; Lindeza, Ana; Richter, S. Helene

doi:10.1093/biosci/biab008

Cited by 7 publications

(11 citation statements)

References 70 publications

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“…In animal research, replicability of experimental findings is complicated by phenotypic plasticity, i.e., the ability of one genotype to exhibit different phenotypes under different environmental conditions [12]. Therefore, phenotypic plasticity increasingly receives attention as an important factor compromising the external validity and replicability of animal research [13][14][15][16][17][18][19][20][21]. Whereas genotypic differences can be eliminated by selective breeding [22][23][24], the environment in which laboratory animals are born and grow up may differ substantially between rearing facilities (RFs) [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level

Jarić

Voelkl²,

Clerc³

et al. 2022

PLoS Biol

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The phenotype of an organism results from its genotype and the influence of the environment throughout development. Even when using animals of the same genotype, independent studies may test animals of different phenotypes, resulting in poor replicability due to genotype-by-environment interactions. Thus, genetically defined strains of mice may respond differently to experimental treatments depending on their rearing environment. However, the extent of such phenotypic plasticity and its implications for the replicability of research findings have remained unknown. Here, we examined the extent to which common environmental differences between animal facilities modulate the phenotype of genetically homogeneous (inbred) mice. We conducted a comprehensive multicentre study, whereby inbred C57BL/6J mice from a single breeding cohort were allocated to and reared in 5 different animal facilities throughout early life and adolescence, before being transported to a single test laboratory. We found persistent effects of the rearing facility on the composition and heterogeneity of the gut microbial community. These effects were paralleled by persistent differences in body weight and in the behavioural phenotype of the mice. Furthermore, we show that environmental variation among animal facilities is strong enough to influence epigenetic patterns in neurons at the level of chromatin organisation. We detected changes in chromatin organisation in the regulatory regions of genes involved in nucleosome assembly, neuronal differentiation, synaptic plasticity, and regulation of behaviour. Our findings demonstrate that common environmental differences between animal facilities may produce facility-specific phenotypes, from the molecular to the behavioural level. Furthermore, they highlight an important limitation of inferences from single-laboratory studies and thus argue that study designs should take environmental background into account to increase the robustness and replicability of findings.

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Section: Introductionmentioning

confidence: 99%

The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level

Jarić

Voelkl²,

Clerc³

et al. 2022

PLoS Biol

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“…When it comes to answering the second question, sometimes the usefulness of predicting new potential strains of pathogens is disputed. Evolutionary outcomes are often unpredictable [ 66 ] and the knowledge achieved with experimental evolution is thus not accomplishable through conventional genome engineering or GOF experiments alone [ 16 , 67–69 ]. Moreover, research on pathogens is not only about their specific features, such as the presence of certain mutations.…”

Section: Evolutionary Aspects Of the Dual-use Discussionmentioning

confidence: 99%

“…Moreover, research on pathogens is not only about their specific features, such as the presence of certain mutations. Rather, evolution experiments inform us about the mechanisms, that is, the evolutionary processes more generally [ 66 ], and thus possible evolutionary trajectories and even potential starting points for countermeasures, for the prevention of highly pathogenic strains. Moreover, in addition to general knowledge of evolutionary processes, understanding the working mechanisms in particular systems [ 48 , 70 , 71 ] and assessing likely evolutionary trajectories of a strain is crucial.…”

Section: Evolutionary Aspects Of the Dual-use Discussionmentioning

confidence: 99%

Integrating evolutionary aspects into dual-use discussion: the cases of influenza virus and enterohemorrhagic Escherichia coli

Selasi

Altinok

Kumar

et al. 2021

Evolution, Medicine, and Public Health

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Research in infection biology aims to understand the complex nature of host-pathogen interactions. While this knowledge facilitates strategies for preventing and treating diseases, it can also be intentionally misused to cause harm. Such dual-use risk is potentially high for highly pathogenic microbes such as Risk Group-3 (RG3) bacteria and RG4 viruses, which could be used in bioterrorism attacks. However, other pathogens such as influenza virus (IV) and enterohaemorrhagic Escherichia coli (EHEC), usually classified as RG2 pathogens, also demonstrate high dual-use risk. As the currently-approved therapeutics against these pathogens are not satisfactorily effective, previous outbreaks of these pathogens caused enormous public fear, media attention, and economic burden. In this interdisciplinary review, we summarize the current perspectives of dual-use research on IV and EHEC, and further highlight the dual-use risk associated with evolutionary experiments with these infectious pathogens. We support the need to carry-out experiments pertaining to pathogen evolution, including to gain predictive insights on their evolutionary trajectories, which cannot be otherwise achieved with stand-alone theoretical models and epidemiological data. However, we also advocate for increased awareness and assessment strategies to better quantify the risks-versus-benefits associated with such evolutionary experiments. In addition to building public trust in dual-use research, we propose that these approaches can be extended to other pathogens currently classified as low risk, but bearing high dual-use potential, given the particular pressing nature of their rapid evolutionary potential.

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“…In these real-time evolution experiments populations are studied across multiple generations (Rose and Garland 2009, 6). They often involve the creation of a series of evolutionary lines that are exposed to a novel environment (Desjardins et al 2021). A well-known laboratory evolution experiment is Richard Lenski's E. coli long-term experimental evolution project (LTEE) at the University of Michigan.…”

Section: Studying the Processes Of Evolution: Experimental Evolution ...mentioning

confidence: 99%

Two kinds of historical explanation in Evolutionary Biology

Kranke

2022

Biol Philos

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Historical explanations in evolutionary biology are commonly characterized as narrative explanations. Examples include explanations of the evolution of particular traits and explanations of macroevolutionary transitions. In this paper I present two case studies of explanations in accounts of pathogen evolution and host-pathogen coevolution, respectively, and argue that one of them is captured well by established accounts of time-sequenced narrative explanation. The other one differs from narrative explanations in important respects, even though it shares some characteristics with them as it is also a population-level historical explanation. I thus argue that the second case represents a different kind of explanation that I call historical explanation of type phenomena. The main difference between the two kinds of explanation is the conceptualization of the explanandum phenomena as particulars or type phenomena, respectively. Narrative explanations explain particulars but also deal with generalization, regularities and type phenomena. Historical explanations of type phenomena, on the other hand, explain multiply realizable phenomena but also deal with particulars. The two kinds of explanation complement each other because they explain different aspects of evolution.

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Beyond Standardization: Improving External Validity and Reproducibility in Experimental Evolution

Cited by 7 publications

References 70 publications

The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level

The rearing environment persistently modulates mouse phenotypes from the molecular to the behavioural level

Integrating evolutionary aspects into dual-use discussion: the cases of influenza virus and enterohemorrhagic Escherichia coli

Two kinds of historical explanation in Evolutionary Biology

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