Recent work on gene concepts has been influenced by recognition of the extent to which RNA transcripts from a given DNA sequence yield different products in different cellular environments. These transcripts are altered in many ways and yield many products based, somehow, on the sequence of nucleotides in the DNA. I focus on alternative splicing of RNA transcripts (which often yields distinct proteins from the same raw transcript) and on 'gene sharing', in which a single gene produces distinct proteins with (...) the exact same amino acid sequence. These are instances of molecular pleiotropy, in which distinct molecules are derived from a single putative gene. In such cases the cellular and external environments play major roles in determining which protein is produced. Where there is molecular pleiotropy, alternative gene concepts are naturally deployed; molecular epigenesis (revision of sequence-based information by altering molecular conformations or by action of non-informational molecules) plays a major role in orderly development. These results show that gene concepts in molecular biology do, and should, have both structural and functional components. They also show the need for a plurality of gene concepts and reveal fundamental difficulties in stabilizing gene concepts solely by reference to nucleotide sequence. (shrink)

Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene–gene interaction, has also been treated as an exception to the Mendelian one gene–one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of (...) biomolecular networks. These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena. (shrink)

Understanding how traits are integrated at the organismal level remains a fundamental problem at the interface of developmental and evolutionary biology. Hormones, regulatory signaling molecules that coordinate multiple developmental and physiological processes, are major determinants underlying phenotypic integration. The probably best example for this is the lipid-like juvenile hormone (JH) in insects. Here we review the manifold effects of JH, the most versatile animal hormone, with an emphasis on the fruit fly Drosophila melanogaster, an organism amenable to both genetics and (...) endocrinology. JH affects a remarkable number of processes and traits in Drosophila development and life history, including metamorphosis, behavior, reproduction, diapause, stress resistance and aging. While many molecular details underlying JH signaling remain unknown, we argue that studying “hormonal pleiotropy” offers intriguing insights into phenotypic integration and the mechanisms underlying life history evolution. In particular, we illustrate the role of JH as a key mediator of life history trade-offs. BioEssays 27:999–1010, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

We contend that social science variables are the product of multiple partly heritable traits. Genetic associations with socioeconomic status (SES) may differ across populations, but this is a consequence of the intermediary traits associated with SES differences also varying. Furthermore, genetic data allow social scientists to make causal statements regarding the aetiology and consequences of SES.

In discussing the relationship between genetically influenced differences and educational attainment (EA), Burt employs the concept of downward causation. I note the similarities between Burt's concept of downward causation and the sociogenomics concept of vertical pleiotropy and argue that her discussion of downward causation introduces an unnecessary normative component. The core problem concerns not the appropriateness of phenotypes that influence EA but mistaken assumptions about which phenotypes are being predicted.

Two classic theories maintain that aging evolves either because of alleles whose deleterious effects are confined to late life or because of alleles with broad pleiotropic effects that increase early‐life fitness at the expense of late‐life fitness. However, empirical studies often reveal positive pleiotropy for fitness across age classes, and recent evidence suggests that selection on early‐life fitness can decelerate aging and increase lifespan, thereby casting doubt on the current consensus. Here, we briefly review these data and promote the (...) simple argument that aging can evolve under positive pleiotropy between early‐ and late‐life fitness when the deleterious effect of mutations increases with age. We argue that this hypothesis makes testable predictions and is supported by existing evidence. (shrink)

The vast majority (> 95%) of single-gene mutations in yeast affect not only the expression of the mutant gene, but also the expression of many other genes. These data suggest the presence of a previously uncharacterized ‘gene expression network’—a set of interactions between genes which dictate gene expression in the native cell environment. Here, we quantitatively analyze the gene expression network revealed by microarray expression data from 273 different yeast gene deletion mutants.(1) We find that gene expression interactions form a (...) robust, error-tolerant ‘scale-free’ network, similar to metabolic pathways(2) and artificial networks such as power grids and the internet.(3-5) Because the connectivity between genes in the gene expression network is unevenly distributed, a scale-free organization helps make organisms resistant to the deleterious effects of mutation, and is thus highly adaptive. The existence of a gene expression network poses practical considerations for the study of gene function, since most mutant phenotypes are the result of changes in the expression of many genes. Using principles of scale-free network topology, we propose that fragmenting the gene expression network via ‘genome-engineering’ may be a viable and practical approach to isolating gene function. BioEssays 24:267–274, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10054. (shrink)

The target article by Charney on behavior genetics/genomics discusses how numerous molecular factors can inform heritability estimations and genetic association studies. These factors find application in the search for genes for behavioral phenotypes, including neuropsychiatric disorders. We elaborate upon how single causal factors can generate multiple phenotypes, and discuss how multiple causal factors may converge on common neurodevelopmental mechanisms.

Genetics was established on a strict particulate conception of heredity. Genetic linkage, the deviation from independent segregation of Mendelian factors, was conceived as a function of the material allocation of the factors to the chromosomes, rather than to the multiple effects (pleiotropy) of discrete factors. Although linkage maps were abstractions they provided strong support for the chromosomal theory of inheritance. Direct Cytogenetic evidence was scarce until X-ray induced major chromosomal rearrangements allowed direct correlation of genetic and cytological rearrangements. Only (...) with the discovery of the polytenic giant chromosomes in Drosophila larvae in the 1930s were the virtual maps backed up by physical maps of the genetic loci. Genetic linkage became a pivotal experimental tool for the examination of the integration of genetic functions in development and in evolution. Genetic mapping has remained a hallmark of genetic analysis. The location of genes in DNA is a modern extension of the notion of genetic linkage. (shrink)

The creeping vole Microtus oregoni exhibits remarkably transformed sex chromosome biology, with complete chromosome drive/drag, X‐Y fusions, sex reversed X complements, biased X inactivation, and X chromosome degradation. Beginning with a selfish X chromosome, I propose a series of adaptations leading to this system, each compensating for deleterious consequences of the preceding adaptation: (1) YY embryonic inviability favored evolution of a selfish feminizing X chromosome; (2) the consequent Y chromosome transmission disadvantage favored X‐Y fusion (“XP”); (3) Xist‐based silencing of Y‐derived (...) XP genes favored a second X‐Y fusion (“XM”); (4) X chromosome dosage‐related costs in XPXM males favored the evolution of XM loss during spermatogenesis; (5) X chromosomal dosage‐related costs in XM0 females favored the evolution of XM drive during oogenesis; and (6) degradation of the non‐recombining XP favored the evolution of biased X chromosome inactivation. I discuss recurrent rodent sex chromosome transformation, and selfish genes as a constructive force in evolution. (shrink)

Advances in developmental genetics and evo-devo in the last several decades have enabled the growth of novel developmental approaches to the classic theme of homology. These approaches depart from the more standard phylogenetic view by contending that homology between morphological characters depends on developmental-genetic individuation and explanation. This article provides a systematic re-examination of the relationship between developmental and phylogenetic homology in light of current evidence from developmental and evolutionary genetics and genomics. I present a qualitative model of the processes (...) that cause de-coupling of morphological and molecular evolution by developmental system drift (DSD), and hypothesize that DSD is a widespread and regular stochastic process that is predictable from parameters such as population size, pleiotropy, and regulatory redundancy. These theoretical findings support an integrative approach in which models of DSD aid in determining when developmental-genetic explanations of homology apply and when other explanations such as stabilizing selection are needed. I argue that a phylogenetic monism about the definition and criteria of homology supports the integration of different explanations into a theory of homology better than pluralism does. (shrink)

Given that natural selection is so powerful at optimizing complex adaptations, why does it seem unable to eliminate genes (susceptibility alleles) that predispose to common, harmful, heritable mental disorders, such as schizophrenia or bipolar disorder? We assess three leading explanations for this apparent paradox from evolutionary genetic theory: (1) ancestral neutrality (susceptibility alleles were not harmful among ancestors), (2) balancing selection (susceptibility alleles sometimes increased fitness), and (3) polygenic mutation-selection balance (mental disorders reflect the inevitable mutational load on the thousands (...) of genes underlying human behavior). The first two explanations are commonly assumed in psychiatric genetics and Darwinian psychiatry, while mutation-selection has often been discounted. All three models can explain persistent genetic variance in some traits under some conditions, but the first two have serious problems in explaining human mental disorders. Ancestral neutrality fails to explain low mental disorder frequencies and requires implausibly small selection coefficients against mental disorders given the data on the reproductive costs and impairment of mental disorders. Balancing selection (including spatio-temporal variation in selection, heterozygote advantage, antagonistic pleiotropy, and frequency-dependent selection) tends to favor environmentally contingent adaptations (which would show no heritability) or high-frequency alleles (which psychiatric genetics would have already found). Only polygenic mutation-selection balance seems consistent with the data on mental disorder prevalence rates, fitness costs, the likely rarity of susceptibility alleles, and the increased risks of mental disorders with brain trauma, inbreeding, and paternal age. This evolutionary genetic framework for mental disorders has wide-ranging implications for psychology, psychiatry, behavior genetics, molecular genetics, and evolutionary approaches to studying human behavior. (Published Online November 9 2006) Key Words: adaptation; behavior genetics; Darwinian psychiatry; evolution; evolutionary genetics; evolutionary psychology; mental disorders; mutation-selection balance; psychiatric genetics; quantitative trait loci (QTL). (shrink)

In multicellular organisms, cells are frequently programmed to die. This makes good sense: cells that fail to, or are no longer playing important roles are eliminated. From the cell’s perspective, this also makes sense, since somatic cells in multicellular organisms require the cooperation of clonal relatives. In unicellular organisms, however, programmed cell death poses a difficult and unresolved evolutionary problem. The empirical evidence for PCD in diverse microbial taxa has spurred debates about what precisely PCD means in the case of (...) unicellular organisms. In this article, we survey the concepts of PCD in the literature and the selective pressures associated with its evolution. We show that definitions of PCD have been almost entirely mechanistic and fail to separate questions concerning what PCD fundamentally is from questions about the kinds of mechanisms that realize PCD. We conclude that an evolutionary definition is best able to distinguish PCD from closely related phenomena. Specifically, we define “true” PCD as an adaptation for death triggered by abiotic or biotic environmental stresses. True PCD is thus not only an evolutionary product but must also have been a target of selection. Apparent PCD resulting from pleiotropy, genetic drift, or trade-offs is not true PCD. We call this “ersatz PCD.”. (shrink)

It is frequently said that biology is emerging from a long phase of reductionism. It would be certainly more correct to say that biologists are abandoning a certain form of reductionism. We describe this past form, and the experiments which challenged the previous vision. To face the difficulties which were met, biologists use a series of concepts and metaphors - pleiotropy, tinkering, epigenetics - the ambiguity of which masks the difficulties, instead of solving them. In a similar way, the (...) word “post-genomics” has different meanings, depending upon who uses it. Which of these meanings will become dominant in the future is an open question. (shrink)

In March 2022 the US Food and Drug Administration (FDA) published a risk assessment of a recent animal gene editing proposal submitted by Acceligen™. The proposal concerned the possibility of changing the cattle genome to obtain a slicker, shorter hair coat. Using CRISPR-Cas9 it was possible to introduce an intentional genomic alteration (IGA) to the prolactin receptor gene (PRLR), thereby producing PRLR-SLICK cattle. The goal was to diminish heat stress in the cattle by enhancing their heat-tolerance. With regard to unintended (...) alterations (i.e., off-target effects), the FDA stated that the IGA posed a low, but still present, risk to animal safety. The aim of this article is to present some initial insights into the welfare issues raised by PRLR-SLICK cattle by addressing the question: Do SLICK cattle have better welfare than non-SLICK cattle when exposed to heat stress? Two potential welfare concerns are examined. The first is pleiotropy, an issue that arises when one gene affects multiple traits. Given the pleiotropic nature of prolactin, it has been suggested that the IGA for SLICK cattle may also affect their hepatic and other functions. The second concern relates not primarily to direct effects on cattle health, but rather to the indirect risk that this more heat-tolerant animal would just be used in the livestock sector under farming conditions that are such that the net welfare improvement would be non-existent. (shrink)

Recent work has shown that a subset of Neandertal‐derived single‐nucleotide polymorphisms (SNP) seems to be playing roles in autism susceptibility. We review this exciting research, as well as the known history of human migrations and interbreeding events between Homo sapiens and Neandertals, all while placing the current work within the context of hybrid dysgenesis and genetic incompatibilities. In addition to these “pushing” factors (purifying selection), we also explore potential “pulling” factors (positive selection), such as antagonistic pleiotropy and balanced polymorphism, (...) which may influence the retention of otherwise weakly deleterious variants within the modern human genome. This work, along with other studies exploring associations between Neandertal‐derived alleles and other neurodivergent conditions, has significant implications for human brain evolution as well as modern human health. (shrink)

: Nearly all of the literature on the ethical, legal, or social issues surrounding genetic tests has proceeded on the assumption that any particular test for a gene mutation yields information about only one disease condition. Even though the phenomenon of pleiotropy, where a single gene has multiple, apparently unrelated phenotypic effects, is widely recognized in genetics, it has not had much significance for genetic testing until recently. In this article, I examine a moral dilemma created by one sort (...) of pleiotropic testing, APOE genotyping, which can yield information about the risk of two different conditions--coronary heart disease and Alzheimer's disease. A physician administering APOE testing for the beneficial purpose of assessing the risk of heart disease may discover medically useless and socially harmful information about the patient's risk of Alzheimer's disease. I explore how much providers should disclose to patients about pleiotropic test results and whether patients are obligated to know as much about their genetic condition as possible. (shrink)

We present a theory of cooperative-competitive intelligence (CCI), its measures, research program, and applications that stem from it. Within the framework of this theory, satisficing sub-optimal behavior is any behavior that does not promote a decrease in the prospective control of the functional action diversity/unpredictability (D/U) potential of the agent or team. This potential is defined as the entropy measure in multiple, context-dependent dimensions. We define the satisficing interval of behaviors as CCI. In order to manifest itself at individual or (...) team level, this capacity harnesses properties such as degeneracy, pleiotropy (pluri-potentiality), synergies, and metastability. Intelligence is embodied because intelligent behavior is deeply dependent on body functionalities, defined as entropy measures. We base our theory on three principles: (a) relativity of functional entropy/ information in agent (team)-environment systems, (b) tendency toward the satisficing level of D/U potential, and (c) tendency toward the non-decreasing D/U potential. The conjunction of these three principles provides existence of sub-optimal behaviors associated with CCI. First, we deal with the problem of how to reduce multidimensional behavior to a concept that accounts for the vast set of scenarios in which CCI is manifested. Secondly, we define and discuss the three interacting principles that underpin CCI behavior as well as providing an outline for a future CCI research program supported by agent￾based modeling and empirical research. Finally, we provide some preliminary practical issues that stem from the theory. (shrink)

This chapter examines the ethical, scientific, and regulatory challenges of preimplantation genetic testing for polygenic conditions (PGT-P) and the use of this technology to select for non-medical traits. PGT-P allows testing for conditions influenced by multiple genes, including schizophrenia, diabetes, and heart disease. Unlike preimplantation genetic testing for monogenic conditions, which provides definitive results, PGT-P offers probabilistic risk scores, raising ethical concerns about environmental influences, disparities in predictive accuracy across ethnicities, and decision-making complexities due to pleiotropy. The chapter explores (...) whether prospective parents should have the freedom to use PGT-P to test for polygenic conditions, and considers issues such as reproductive liberty, the potential to prevent debilitating conditions, and the importance of comprehensive genetic counselling. It also critically evaluates whether PGT-P should be used for trait selection, focusing on intelligence. Arguments raised in the previous chapter, such as procreative beneficence and the open future argument will be revisited, and new ethical objections introduced, including the therapeutic/non-therapeutic distinction and the ‘playing God’ argument. In conclusion, the chapter argues that while PGT-P poses unique challenges, it may be ethically permissible. (shrink)

Although sexual antagonism may have played a role in forming some sex chromosome systems, there appears to be little empirical or theoretical justification in assuming that it is the driving force in all cases of sex chromosome evolution. In many species, sex chromosomes have diverged in size and shape through the accumulation of mutations in regions of suppressed recombination. It is commonly assumed that recombination is suppressed in sex chromosomes due to selection to resolve sexually antagonistic pleiotropy. However, the (...) requirement for a sex chromosome‐specific mechanism for suppressing recombination is questionable, since more general models of recombination suppression on autosomes also appear to be applicable to sex chromosomes. Direct tests of the predictions of the sexual antagonism hypothesis offer only limited support in specific sex chromosome systems and circumstantial evidence remains open to interpretation. (shrink)

Like several other classes of hormones, the class of plant hormones called auxins exert myriad effects on cell development. While auxins are most noted for inducing cell elongation, they are also involved in cell division, cell differentiation, cell and organ polarity, and wound responsiveness. Consistent with this pleiotropy, is the recent identification of several putative auxin receptors that in theory could represent the primary elements of more than one auxin signal pathway leading to distinct responses or leading in parallel (...) to a single response. Our current working hypothesis is that some auxin‐mediated responses may be mediated by multiple receptors. We describe some of what is known about each of the new putative receptors and elaborate on the hypothesis using the example of cell elongation. Specifically for auxin‐induced elongation, we propose that two rapid events, specific gene transcription and cell wall acidification, are separately mediated by at least two receptors, acting in the nucleus and at the plasma membrane, respectively. (shrink)

Introduction to complexity and complex systems -- Introduction to large linear systems -- Introduction to biochemical oscillators and nonlinear biochemical systems -- Modularity, redundancy, degeneracy, pleiotropy and robustness in complex biological systems -- The evolution of biological complexity; invertebrate immune systems -- Irreducible and specified complexity in living systems -- The complex adaptive and innate human immune systems -- Complexity in quasispecies : microRNAs -- Introduction to complexity in economic systems -- Complexity in quasispecies : micrornas -- Dealing with (...) complexity. (shrink)

Ecological Immunology assumes that immunological defenses must be minimized in terms of cost (energy expenditure). To reach this goal, a complex and still largely unexplored strategy has evolved to assure survival. From invertebrates to vertebrates, an integrated immune–neuroendocrine response appears to be crucial for the hierarchical redistribution of resources within the body according to the specific ecological demands. Thus, on the basis of experimental data on the intimate relationship between stress and immune responses that has been maintained during evolution, we (...) argue that a broader perspective based on the integration of immune and neuroendocrine responses should be adopted to describe the comprehensive strategy that the body utilizes to adapt to dynamic environmental conditions. We discuss the hypothesis that a bow‐tie architecture might be suitable to describe the variety of immune–neuroendocrine inputs that continuously target cells and organs while, at the same time, fulfilling the basic requirement of minimizing the cost of immune–neuroendocrine responses. Bow‐tie architectures are able to convert a variety of stimuli (fan in) into a wide range of fine‐tuned responses (fan out) by passing through the integrating activity of a core (knot) constituted by a limited number of elements. Finally, we argue that the ecologically negotiated immune–neuroendocrine strategies may have deleterious effects in the post‐reproductive period of life when, at least in humans, chronic, low‐grade, systemic inflammation develops, in accordance with the antagonistic pleiotropy theory of aging. BioEssays 30:868–874, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Genetic analysis of Drosophil has provided evidence in support of two proposed evolutionary genetic mechanisms of aging: mutation accumulation and antagonistic pleiotropy. Both mechanisms result from the lack of natural selection acting on old organisms. Analyses of large numbers of flies have revealed that mortality rates do not continue to rise with age as previously thought, but plateau at advanced ages. This phenomenon has implications both for models and for definitions of aging, and may be explained by the evolutionary (...) theories. The physiological processes and genes most relevant to aging are being identified using Drosophila lines selected in the laboratory for postponed senescence. Oxidative stress and insufficient metabolic reserves/capacity may be particularly important factors in limiting the fruitfly lifespan. Genes which exhibit aging‐related changes in expression are now being identified. Transgenic flies are being used to analyze the mechanisms of such aging‐related gene expression, and to test the effects of specific genes on aging and aging‐related deterioration. (shrink)

Genomes are inherently unstable because of the need for DNA sequence variation as a substrate for evolution through natural selection. However, most multicellular organisms have postmitotic tissues, with limited opportunity for selective removal of cells harboring persistent damage and deleterious mutations, which can therefore contribute to functional decline, disease, and death. Key in this process is the role of genome maintenance, the network of protein products that repair DNA damage and signal DNA damage response pathways. Genome maintenance is beneficial early (...) in life by swiftly eliminating DNA damage or damaged cells, facilitating rapid cell proliferation. However, at later ages accumulation of unrepaired damage and mutations, as well as ongoing cell depletion, promotes cancer, atrophy, and other deleterious effects associated with aging. As such, genome maintenance and its phenotypic sequelae provide yet another example of antagonistic pleiotropy in aging and longevity. (shrink)

A great deal of progress has recently been made in characterizing the “mechanisms of aging.” A comparison with the mechanisms of development shows that the two sets of mechanisms are different; nevertheless, mechanisms of aging are conditioned by what happens during development. Aging and development also share some characteristics, such as a similar difficulty in attributing a precise temporal boundary to these processes. Other characteristics seem more specific to aging, such as the role of external (to the organism) and stochastic (...) events in its progression. In fact, both development and aging are historical processes with a mixture of stochastic events and deterministic processes, the ratio of the two being different in each process. Therefore, it is concluded that aging does not fit with a broad, lifelong conception of development. (shrink)

For at least a century it has been known that multiple factors play a role in the development of complex traits, and yet the notion that there are genes “for” such traits, which traces back to Mendel, is still widespread. In this paper, we illustrate how the Mendelian model has tacitly encouraged the idea that we can explain complexity by reducing it to enumerable genes. By this approach many genes associated with simple as well as complex traits have been identified. (...) But the genetic architecture of biological traits, or how they are made, remains largely unknown. In essence, this reflects the tension between reductionism as the current “modus operandi” of science, and the emerging knowledge of the nature of complex traits. Recent interest in systems biology as a unifying approach indicates a reawakened acceptance of the complexity of complex traits, though the temptation is to replace “gene for” thinking by comparably reductionistic “network for” concepts. Both approaches implicitly mix concepts of variants and invariants in genetics. Even the basic question is unclear: what does one need to know to “understand” the genetic basis of complex traits? New operational ideas about how to deal with biological complexity are needed. (shrink)

Adaptive phenotypic plasticity allows organisms to cope with environmental variability, and yet, despite its adaptive significance, phenotypic plasticity is neither ubiquitous nor infinite. In this review, we merge developmental and population genetic perspectives to explore costs and limits on the evolution of plasticity. Specifically, we focus on the role of modularity in developmental genetic networks as a mechanism underlying phenotypic plasticity, and apply to it lessons learned from population genetic theory on the interplay between relaxed selection and mutation accumulation. We (...) argue that the environmental specificity of gene expression and the associated reduction in pleiotropic constraints drive a fundamental tradeoff between the range of plasticity that can be accommodated and mutation accumulation in alternative developmental networks. This tradeoff has broad implications for understanding the origin and maintenance of plasticity and may contribute to a better understanding of the role of plasticity in the origin, diversification, and loss of phenotypic diversity. (shrink)

Proponents of the standard evolutionary biology paradigm explain human “altruism” in terms of either nepotism or strict reciprocity. On that basis our underlying nature is reduced to a function of inclusive fitness: human nature has to be totally selfish or nepotistic. Proposed here are three possible paths to giving costly aid to nonrelatives, paths that are controversial because they involve assumed pleiotropic effects or group selection. One path is pleiotropic subsidies that help to extend nepotistic helping behavior from close family (...) to nonrelatives. Another is “warfare”—if and only if warfare recurred in the Paleolithic. The third and most plausible hypothesis is based on the morally based egalitarian syndrome of prehistoric hunter-gatherers, which reduced phenotypic variation at the within-group level, increased it at the between-group level, and drastically curtailed the advantages of free riders. In an analysis consistent with the fundamental tenets of evolutionary biology, these three paths are evaluated as explanations for the evolutionary development of a rather complicated human social nature. (shrink)

No universally accepted notion of evolvability is available, focus being alternatively put onto either genetic or phenotypic change. The heuristic power of this concept is best found when considering the intricacies of the genotype→phenotype map, which is not necessarily predictable, expression of variation depending on the structure of gene networks and especially on the modularity and robustness of developmental systems. We can hardly ignore evolvability whenever studying the role of cryptic variation in evolution, the often pervious boundary between phenotypic plasticity (...) and the expression of a genetic polymorphism, the major phenotypic leaps that the mechanisms of development can produce based on point mutations, or the morphological stasis that reveals how robust a developmental process can be in front of genetic change. Evolvability is subject itself to evolution, but it is still uncertain to what extent there is positive selection for enhanced evolvability, or for evolvability biased in a specific direction. (shrink)

Precise spatiotemporal control of gene expression during normal development and cell differentiation is achieved by the combined action of proximal (promoters) and distal (enhancers) cis‐regulatory elements. Recent studies have reported that a subset of promoters, termed Epromoters, works also as enhancers to regulate distal genes. This new paradigm opened novel questions regarding the complexity of our genome and raises the possibility that genetic variation within Epromoters has pleiotropic effects on various physiological and pathological traits by differentially impacting multiple proximal and (...) distal genes. Here, we discuss the different observations pointing to an important role of Epromoters in the regulatory landscape and summarize the evidence supporting a pleiotropic impact of these elements in disease. We further hypothesize that Epromoter might represent a major contributor to phenotypic variation and disease. (shrink)

Observing adaptive evolution is difficult. In the fossil record, phenotypic evolution happens much more slowly than in artificial selection experiments or in experimental evolution. Yet measures of selection on phenotypic traits, with high heritabilities, suggest that phenotypic evolution should also be rapid in the wild, and this discrepancy often remains even after accounting for correlations between different traits (i.e. making predictions using the multivariate version of the breeder's equation). Are fitness correlations with quantitative traits adequate measures of selection in the (...) wild? We should instead view fitnesses as average properties of genotypes, while acknowledging that they can be environment‐dependent. Populations will tend to remain at fitness equilibria, once these are attained, and phenotypes will then be stable. Thus, studying the causes of adaptive change at a genotypic rather than phenotypic level may reveal that, typically, it is occurring too slowly to be easily observed. (shrink)

The current tendency to moderate expectations that DNA barcode can be a method of discovering new species is due to the essentialist interpretation of this scientific analogy that is conceptually unsustainable. Something similar has happened in the philosophical field with the weakening of the initial versions of intrinsic biological essentialism. To examine the nature of this transition, I propose two principles that define a moderate EBI: one that assumes that the history of the taxon is metaphysically dependent on the evolution (...) of its intrinsic properties and another that assumes the necessary coextensivity between the intrinsic properties that explain the phenotype of the species and the bearers of identity conditions of a species. I argue that both principles are conceptually and empirically unsatisfactory. (shrink)

This chapter introduces the core of the evolutionary biology of death, namely, Medawar’s mutation accumulation, and Williams’ antagonistic pleiotropy; it situates this latter theory within Williams thought, especially his critique of group selection.

This chapter focuses on the notion of trade-off, as it has been used by biologists in order to make sense of the antagonistic pleiotropy account and the Disposable Soma Theory. I enquire about the currency that is underpinning these trade-offs and show that the assumptions about discounting rate are crucial. I explain that several trade-offs with several currencies take place at the same time and that no theories can reduce all of them into one specific trade-off with a single (...) currency and a single discounting rate. Based on recent models I show that the plurality of trade-offs leaves room for stochasticity and for constraints, which limits the explanatory role of economic concepts such as trade-offs, investment, and resources, with respect to the evolutionary biology of death. (shrink)