Complex, multigenic biological traits are shaped by the emergent interaction of proteins being the main functional units at the molecular scale. Based on a phenomenological approach, algorithms for quantifying two different aspects of emergence were introduced (Wegner and Hao in Progr Biophys Mol Biol 161:54–61, 2021) describing: (i) pairwise reciprocal interactions of proteins mutually modifying their contribution to a complex trait (denoted as weak emergence), and (ii) formation of a new, complex trait by a set of n ‘constitutive’ proteins at (...) concentrations exceeding individual threshold values (strong emergence). The latter algorithm is modified here to take account of protein redundancy with respect to a complex trait (‘full redundancy’). Irreducibility is considered a necessary and sufficient criterion for strong biological emergence; if one constitutive protein is missing, or its concentration drops below the threshold the trait is lost. A definition based on ‘unpredictability’ is dismissed, because this criterion is irrelevant for the evolution of a complex trait, and apparent unpredictability may rather reflect our basic deficits in understanding unless we can provide an unequivocal proof for it. The phenomenological approach advocated here allows to identify hidden rules according to which strongly emergent traits may be organized. This is of high value for understanding the evolution of complex traits which seems to require the saltational advent of all constitutive proteins ‘in one turn’ to arrive at a functional trait providing for an improved fitness of the organism. Rather than being a purely random process, it may be guided by fundamental structural principles. (shrink)

Although the field of psychiatry has witnessed the proliferation of studies on Gene x Environment (GxE) interactions, still limited is the knowledge we possess of GxE interactions regarding developmental disorders. In this perspective paper, we discuss why GxE interaction studies are needed to broaden our knowledge of developmental disorders. We also discuss the different roles of hazardous versus self-generated environmental factors and how these types of factors may differentially engage with an individual’s genetic background in predicting a resulting phenotype. Then, (...) we present exemplar studies that highlight the role of GxE in predicting atypical developmental trajectories as well as provide insight regarding treatment outcomes. Supported by these examples, we explicate the need to move beyond merely examining statistical interactions between genes and the environment, and to investigate specific genetic susceptibility and environmental contexts that drive developmental disorders. We propose that further parsing of genetic and environmental components is required to fully understand the unique contribution of each factor to the etiology of developmental disorders. Finally, with a greater appreciation of the complexities of GxE interaction, this discussion will converge upon the potential implications for clinical and translational research. (shrink)

Mutational robustness facilitates evolutionary innovations. Gene duplications are unique kinds of mutations, in that they generally increase such robustness. The frequent association of gene duplications in regulatory networks with evolutionary innovation is thus a special case of a general mechanism linking innovation to robustness. The potential power of this mechanism to promote evolutionary innovations on large time scales is illustrated here with several examples. These include the role of gene duplications in the vertebrate radiation, flowering plant evolution and heart development, (...) which encompass some of the most striking innovations in the evolution of life. BioEssays 30:367–373, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

This paper argues in defense of theanti-reductionist consensus in the philosophy ofbiology. More specifically, it takes issues with AlexRosenberg's recent challenge of this position. Weargue that the results of modern developmentalgenetics rather than eliminating the need forfunctional kinds in explanations of developmentactually reinforce their importance.

The robustness of biological processes to perturbations has so far been mainly explored in unicellular organisms; multicellular organisms have been studied for developmental processes or in the special case of redundancy between gene duplicates. Here we explore the robustness of cell biological mechanisms of multicellular organisms in an evolutionary context. We propose that the reuse of similar cell biological mechanisms in different cell types of the same organism has evolutionary implications: (1) the maintenance of apparently redundant mechanisms over evolutionary time (...) may in part be explained by their differential requirement in various cell types; (2) the relative requirement for two alternative mechanisms may evolve among homologous cells in different organisms. We present examples of cell biological processes, such as centrosome separation in prophase, spindle formation or cleavage furrow positioning, that support the first proposition. We propose experimental tests of these hypotheses. (shrink)

We review the various factors that limit adaptation by natural selection. Recent discussion of constraints on selection and, conversely, of the factors that enhance “evolvability”, have concentrated on the kinds of variation that can be produced. Here, we emphasise that adaptation depends on how the various evolutionary processes shape variation in populations. We survey the limits that population genetics places on adaptive evolution, and discuss the relationship between disparate literatures. BioEssays 22:1075–1084, 2000. © 2000 John Wiley & Sons, Inc.

The “DNA is a program” metaphor is still widely used in Molecular Biology and its popularization. There are good historical reasons for the use of such a metaphor or theoretical model. Yet we argue that both the metaphor and the model are essentially inadequate also from the point of view of Physics and Computer Science. Relevant work has already been done, in Biology, criticizing the programming paradigm. We will refer to empirical evidence and theoretical writings in Biology, although our arguments (...) will be mostly based on a comparison with the use of differential methods (in Molecular Biology: a mutation or alike is observed or induced and its phenotypic consequences are observed) as applied in Computer Science and in Physics, where this fundamental tool for empirical investigation originated and acquired a well-justified status. In particular, as we will argue, the programming paradigm is not theoretically sound as a causal(as in Physics) or deductive(as in Programming) framework for relating the genome to the phenotype, in contrast to the physicalist and computational grounds that this paradigm claims to propose. (shrink)

The phenomenon of ‘canalization’ ‐ the genetic capacity to buffer developmental pathways against mutational or environmental perturbations ‐ was first characterized in the late 1930s and early 1940s. Despite enormous subsequent progress in understanding the nature of the genetic material and the molecular basis of gene expression, there have been few attempts to interpret the classical work on canalization in molecular genetic terms. Some recent findings, however, bear on one form of canalization, ‘genetic canalization’, the stabilization of development against mutational (...) effects. These data indicate that co‐expressed paralogous genes can function as mutual ‘back‐up’ elements in developmental processes. Paralogues, however, are far from the only basis of canalization: other genetic sources can be readily envisaged and some of these are described here. The evolutionary questions about genetic canalization and the mechanistic questions about developmental instability that still need to be addressed are also briefly discussed. (shrink)

The multiplicity of deubiquitinating enzymes (DUBs) encoded by vertebrate genomes is partly attributable to whole genome duplication events that occurred early in chordate evolution. By surveying the literature for the largest family of DUBs (the ubiquitin-specific proteases), extensive functional redundancy for duplicated genes has been confirmed as opposed to singletons. Dramatically conflicting results have been reported for loss of function studies conducted through RNA interference as opposed to inactivating mutations, but the contradictory findings can be reconciled by a recently proposed (...) compensatory mechanism involving nonsense-mediated RNA degradation. Duplicated genes are often inactivated to become pseudogenes, and it is proposed that such is the fate of the USP15 gene of zebrafish, a commonly used model system. As it is reviewed here, these observations have implications not only for the interpretation of model system phenotypes but also for therapeutic interventions designed to target DUBs. (shrink)