Finding the way in phenotypic space: the origin and maintenance of constraints on organismal form

BACKGROUND: One of the all-time questions in evolutionary biology regards the evolution of organismal shapes, and in particular why certain forms appear repeatedly in the history of life, others only seldom and still others not at all. Recent research in this field has deployed the conceptual framework of constraints and natural selection as measured by quantitative genetic methods. SCOPE: In this paper I argue that quantitative genetics can by necessity only provide us with useful statistical summaries that may lead researchers to formulate testable causal hypotheses, but that any inferential attempt beyond this is unreasonable. Instead, I suggest that thinking in terms of coordinates in phenotypic spaces, and approaching the problem using a variety of empirical methods (seeking a consilience of evidence), is more likely to lead to solid inferences regarding the causal basis of the historical patterns that make up most of the data available on phenotypic evolution.     

By-product runaway evolution by adaptive mate choice: A behavioural aspect of sexual selection

Summary From a behavioural perspective on adaptive female choice, I developed a by-product runaway model of adaptive mate choice. The model illustrates the evolution of the tail size of peacocks. I consider the causal mechanisms of adaptive female choice: (1) why (ultimate reasons); (2) how (proximate mechanisms). Assumptions are developed based on these behavioural aspects. For (1) ultimate reasons, I assume that many male losers (low-fitness males) always occur due to genetic and environmental uncertainty (A-1). For (2) proximate mechanisms, I assume that losers tend to differ in the expression of a fitness-sensitive trait (an ultimate target, e.g. body size; A-2), that the fitness-sensitive trait correlates with a secondary sexual trait (a proximate cue, e.g. allometry in body size and tail size; (A-3), and that the cue trait has a genetic basis that is independent of the target trait (e.g. a genetic basis in tail ratio to body size; A-4). The model's results are: persistent female choice by means of a proximate cue (R-1); by-product selection on the independent genetic basis of the cue (R-2); and the non-adaptive or maladaptive runaway evolution of the male proximate cue (R-3). In this model, female mate preferences are non-arbitrary and adaptive, whereas the resulting evolution of male secondary sexual traits is non-adaptive in the sense of survival selection.     

Evolutionary quantitative genetics of nonlinear developmental systems

In quantitative genetics, the effects of developmental relationships among traits on microevolution are generally represented by the contribution of pleiotropy to additive genetic covariances. Pleiotropic additive genetic covariances arise only from the average effects of alleles on multiple traits, and therefore the evolutionary importance of nonlinearities in development is generally neglected in quantitative genetic views on evolution. However, nonlinearities in relationships among traits at the level of whole organisms are undeniably important to biology in general, and therefore critical to understanding evolution. I outline a system for characterizing key quantitative parameters in nonlinear developmental systems, which yields expressions for quantities such as trait means and phenotypic and genetic covariance matrices. I then develop a system for quantitative prediction of evolution in nonlinear developmental systems. I apply the system to generating a new hypothesis for why direct stabilizing selection is rarely observed. Other uses will include separation of purely correlative from direct and indirect causal effects in studying mechanisms of selection, generation of predictions of medium‐term evolutionary trajectories rather than immediate predictions of evolutionary change over single generation time‐steps, and the development of efficient and biologically motivated models for separating additive from epistatic genetic variances and covariances.     

Novel integrative genomics strategies to identify genes for complex traits

Forward genetics is a common approach to dissecting complex traits like common human diseases. The ultimate aim of this approach was the identification of genes that are causal for disease or other phenotypes of interest. However, the forward genetics approach is by definition restricted to the identification of genes that have incurred mutations over the course of evolution or that incurred mutations as a result of chemical mutagenesis, and that as a result lead to disease or to variations in other phenotypes of interest. Genes that harbour no such mutations, but that play key roles in parts of the biological network that lead to disease, are systematically missed by this class of approaches. Recently, a class of novel integrative genomics approaches has been devised to elucidate the complexity of common human diseases by intersecting genotypic, molecular profiling, and clinical data in segregating populations. These novel approaches take a more holistic view of biological systems and leverage the vast network of gene–gene interactions, in combination with DNA variation data, to establish causal relationships among molecular profiling traits and Fbetween molecular profiling and disease (or other classic phenotypes). A number of novel genes for disease phenotypes have been identified as a result of these approaches, highlighting the utility of integrating orthogonal sources of data to get at the underlying causes of disease.     

First Steps in Eukaryogenesis: Physical Phenomena in the Origin and Evolution of Chromosome Structure

Our present understanding of the origin and evolution of chromosomes differs considerably from current understanding of the origin and evolution of the cell itself. Chromosome origins have been less prominent in research, as the emphasis has not shifted so far appreciably from the phenomenon of primeval nucleic acid encapsulation to that of the origin of gene organization, expression, and regulation. In this work we discuss some reasons why preliminary steps in this direction are being taken. We have been led to examine properties that have contributed to raise the ancestral prokaryotic programmes to a level where we can appreciate in eukaryotes a clear departure from earlier themes in the evolution of the cell from the last common ancestor. We shift our point of view from evolution of cell morphology to the point of view of the genes. In particular, we focus attention on possible physical bases for the way transmission of information has evolved in eukaryotes, namely, the inactivation of whole chromosomes. The special case of the inactivation of the X chromosome in mammals is discussed, paying particular attention to the physical process of the spread of X inactivation in monotremes (platypus and echidna). When experimental data is unavailable some theoretical analysis is possible based on the idea that in certain cases collective phenomena in genetics, rather than chemical detail, are better correlates of complex chemical processes.     

Agential autonomy and biological individuality

What is a biological individual? How are biological individuals individuated? How can we tell how many individuals there are in a given assemblage of biological entities? The individuation and differentiation of biological individuals are central to the scientific understanding of living beings. I propose a novel criterion of biological individuality according to which biological individuals are autonomous agents. First, I articulate an ecological–dynamical account of natural agency according to which, agency is the gross dynamical capacity of a goal-directed system to bias its repertoire to respond to its conditions as affordances. Then, I argue that agents or agential dynamical systems can be agentially dependent on, or agentially autonomous from, other agents and that this agential dependence/autonomy can be symmetrical or asymmetrical, strong or weak. Biological individuals, I propose, are all and only those agential dynamical systems that are strongly agentially autonomous. So, to determine how many individuals there are in a given multiagent aggregate, such as multicellular organism, a colony, symbiosis, or a swarm, we first have to identify how many agential dynamical systems there are, and then what their relations of agential dependence/autonomy are. I argue that this criterion is adequate to the extent that it vindicates the paradigmatic cases, and explains why the paradigmatic cases are paradigmatic, and why the problematic cases are problematic. Finally, I argue for the importance of distinguishing between agential and causal dependence and show the relevance of agential autonomy for understanding the explanatory structure of evolutionary developmental biology.     

The genetics of species differences

Species are separated by reproductive isolation as well as by more 'ordinary' differences in morphology and behavior that play no necessary role in blocking gene flow. Although a great deal is now known about the genetics of reproductive isolation, we are only beginning to understand the genetic basis of ordinary phenotypic differences between species. I review what is known about the number of genes involved in such differences, as well as about the role of major genes and epistasis in the evolution of these differences. I also compare and contrast these findings with those on the genetics of reproductive isolation.     

The DNA database search controversy

A recent article in Biometrics (Stockmarr, 1999, 55, 671-677) has generated correspondence (56, 1274-1277; 57, 976-980) reigniting a controversy started by a 1996 report on DNA profile evidence issued by the U.S. National Research Council (NRC). The issue concerns the evidential weight of a DNA profile match when the match results from a search through a profile database. The views of both Stockmarr and the NRC report conflict with those of many statisticians working in the area, and the differing viewpoints lead to dramatically different assessments of evidence. I outline reasons why Stockmarr and the NRC report are wrong. I also briefly discuss possible reasons why forensic applications tend to be problematic for statisticians.     

The social evolution of bacterial pathogenesis

Many of the genes responsible for the virulence of bacterial pathogens are carried by mobile genetic elements that can be transferred horizontally between different bacterial lineages. Horizontal transfer of virulence-factor genes has played a profound role in the evolution of bacterial pathogens, but it is poorly understood why these genes are so often mobile. Here, I present a hypothetical selective mechanism maintaining virulence-factor genes on horizontally transmissible genetic elements. For virulence factors that are secreted extracellularly, selection within hosts may favour mutant 'cheater' strains of the pathogen that do not produce the virulence factor themselves but still benefit from factors produced by other members of the pathogen population within a host. Using simple mathematical models, I show that if this occurs then selection for infectious transmission between hosts favours pathogen strains that can reintroduce functional copies of virulence-factor genes into cheaters via horizontal transfer, forcing them to produce the virulence factor. Horizontal gene transfer is thus a novel mechanism for the evolution of cooperation. I discuss predictions of this hypothesis that can be tested empirically and its implications for the evolution of pathogen virulence.     

Designing for emotion (among other things)

Using computational approaches to emotion in design appears problematic for a range of technical, cultural and aesthetic reasons. After introducing some of the reasons as to why I am sceptical of such approaches, I describe a prototype we built that tried to address some of these problems, using sensor-based inferencing to comment upon domestic ‘well-being’ in ways that encouraged users to take authority over the emotional judgements offered by the system. Unfortunately, over two iterations we concluded that the prototype we built was a failure. I discuss the possible reasons for this and conclude that many of the problems we found are relevant more generally for designs based on computational approaches to emotion. As an alternative, I advocate a broader view of interaction design in which open-ended designs serve as resources for individual appropriation, and suggest that emotional experiences become one of several outcomes of engaging with them.     

The concept of mechanism in biology

The concept of mechanism in biology has three distinct meanings. It may refer to a philosophical thesis about the nature of life and biology ('mechanicism'), to the internal workings of a machine-like structure ('machine mechanism'), or to the causal explanation of a particular phenomenon ('causal mechanism'). In this paper I trace the conceptual evolution of 'mechanism' in the history of biology, and I examine how the three meanings of this term have come to be featured in the philosophy of biology, situating the new 'mechanismic program' in this context. I argue that the leading advocates of the mechanismic program (i.e., Craver, Darden, Bechtel, etc.) inadvertently conflate the different senses of 'mechanism'. Specifically, they all inappropriately endow causal mechanisms with the ontic status of machine mechanisms, and this invariably results in problematic accounts of the role played by mechanism-talk in scientific practice. I suggest that for effective analyses of the concept of mechanism, causal mechanisms need to be distinguished from machine mechanisms, and the new mechanismic program in the philosophy of biology needs to be demarcated from the traditional concerns of mechanistic biology.     

A lost cause? Fundamental problems for causal theories of parenthood

In this paper, I offer a critique of (actual and possible) causal theories of parenthood. I do not offer a competing account of who incurs parental obligations and why; rather, I aim to show that there are fundamental problems for any account of who acquires parental obligations and why by appeal to causal responsibility for a child’s existence. I outline and justify three criteria that any plausible causal account of parental obligation must meet, and demonstrate that attempting to fulfil all three criteria simultaneously will give rise to one or both of two potentially insurmountable dilemmas.     

A new stage in the development of genetics and term "epigenetics"

Genetics requires verification of the notion of gene. In this article, DNA and DNA parts are proposed to be named progenes, while the term gene refers to the informational products produced on DNA. These are RNA genes, protein genes, and DNA genes (transposable elements). The focus of genetics is thus switched from characters of intraspecies difference to characters of intraspecies similarity. Regulatory genes controlling ontogeny (ontogenes) become the main object of research. These genes can be isolated by methods of both reverse and direct genetics. The properties of ontogene mutations, produced by methods of direct genetics, are described. The problematic of epigenetics is related to the expression of ontogenes. The term epigenetics is not correct because of its ambiguity.     

Genetic Variance–covariance Matrices: A Critique of the Evolutionary Quantitative Genetics Research Program

This paper outlines a critique of the use of the genetic variance–covariance matrix (G), one of the central concepts in the modern study of natural selection and evolution. Specifically, I argue that for both conceptual and empirical reasons, studies of G cannot be used to elucidate so-called constraints on natural selection, nor can they be employed to detect or to measure past selection in natural populations – contrary to what assumed by most practicing biologists. I suggest that the search for a general solution to the difficult problem of identifying causal structures given observed correlation’s has led evolutionary quantitative geneticists to substitute statistical modeling for the more difficult, but much more valuable, job of teasing apart the many possible causes underlying the action of natural selection. Hence, the entire evolutionary quantitative genetics research program may be in need of a fundamental reconsideration of its goals and how they correspond to the array of mathematical and experimental techniques normally employed by its practitioners.     

Chromosomal instability and human cancer

Genetic instability is a defining feature of human cancer. The main type of genetic instability, chromosomal instability (CIN), enhances the rate of gross chromosomal changes during cell division. CIN is brought about by mutations of CIN genes, i.e. genes that are involved in maintaining the genomic integrity of the cell. A major question in cancer genetics is whether genetic instability is a cause and hence a driving force of tumorigenesis. A mathematical framework for studying the somatic evolution of cancer sheds light onto the causal relations between CIN and human cancer.     

Does evolution in body patterning genes drive morphological change—or vice versa?

Increased understanding of the regulation of body patterning genes in development, especially the homeotic genes, has led to the revival of ideas suggesting that “saltational” modes of evolution are important. However, such models are problematic on the grounds of functional continuity and population genetics, and the more dramatic scenarios rely on an overinterpretation of the taxonomic hierarchy. This article proposes an alternative model for the evolution of Hox gene expression, stressing the need for incremental functional integration. One surprising implication of the model would be that mutations in Hox genes and their regulators have virtually no primary role in driving morphological evolution. Rather, morphological change through microevolutionary adaptation comes first, with Hox expression shifting only afterwards, presumably to make the building of the new body pattern more efficient or more stable. Such a model has affinities to Waddington's “genetic assimilation” but invokes discrete rather than continuous shifts in control of a particular morphology. BioEssays 21:326–332, 1999. © 1999 John Wiley & Sons, Inc.     

A new stage in the development of genetics and term epigenetics

Genetics requires verification of the notion of gene. In this article, DNA and DNA parts are proposed to be named progenes, while the term gene refers to the informational products produced on DNA. These are RNA genes, protein genes, and DNA genes (transposable elements). The focus of genetics is switched today from characters of intraspecies difference to characters of intraspecies similarity. Regulatory genes controlling ontogeny (ontogenes) become the main object of research. These genes can be isolated by methods of both reverse and direct genetics. The properties of ontogene mutations, isolated by methods of direct genetics, are described. The problematic of epigenetics is related to the expression of ontogenes. The term epigenetics is not correct because of its ambiguity.