The linear sequence specification of a gene product is not provided by the target DNA sequence alone but by the mechanisms of gene expressions. The main actors of these mechanisms, proteins and functional RNAs, relay environmental information to the genome with important consequences to sequence selection and processing. This `postgenomic' reality has implications for our understandings of development not as predetermined by genes but as an epigenetic process. Critics of genetic determinism have long argued that the activity of `genes' and (...) hence their contribution to the phenotype depends on intra- and extraorganismal `environmental' elements. As will be shown here, even the mere physical existence of a `gene' is dependent on its phenotypic context. (shrink)

In eukaryotes, RNA trans‐splicing is an important RNA‐processing form for the end‐to‐end ligation of primary transcripts that are derived from separately transcribed exons. So far, three different categories of RNA trans‐splicing have been found in organisms as diverse as algae to man. Here, we review one of these categories: the trans‐splicing of discontinuous group II introns, which occurs in chloroplasts and mitochondria of lower eukaryotes and plants. Trans‐spliced exons can be predicted from DNA sequences derived from a large number of (...) sequenced organelle genomes. Further molecular genetic analysis of mutants has unravelled proteins, some of which being part of high‐molecular‐weight complexes that promote the splicing process. Based on data derived from the alga Chlamydomonas reinhardtii, a model is provided which defines the composition of an organelle spliceosome. This will have a general relevance for understanding the function of RNA‐processing machineries in eukaryotic organelles. (shrink)

The theory of concepts advanced in the dissertation aims at accounting for a) how a concept makes successful practice possible, and b) how a scientific concept can be subject to rational change in the course of history. Traditional accounts in the philosophy of science have usually studied concepts in terms only of their reference; their concern is to establish a stability of reference in order to address the incommensurability problem. My discussion, in contrast, suggests that each scientific concept consists of (...) three components of content: 1) reference, 2) inferential role, and 3) the epistemic goal pursued with the concept's use. I argue that in the course of history a concept can change in any of these three components, and that change in one component—including change of reference—can be accounted for as being rational relative to other components, in particular a concept's epistemic goal.This semantic framework is applied to two cases from the history of biology: the homology concept as used in 19th and 20th century biology, and the gene concept as used in different parts of the 20th century. The homology case study argues that the advent of Darwinian evolutionary theory, despite introducing a new definition of homology, did not bring about a new homology concept (distinct from the pre-Darwinian concept) in the 19th century. Nowadays, however, distinct homology concepts are used in systematics/evolutionary biology, in evolutionary developmental biology, and in molecular biology. The emergence of these different homology concepts is explained as occurring in a rational fashion. The gene case study argues that conceptual progress occurred with the transition from the classical to the molecular gene concept, despite a change in reference. In the last two decades, change occurred internal to the molecular gene concept, so that nowadays this concept's usage and reference varies from context to context. I argue that this situation emerged rationally and that the current variation in usage and reference is conducive to biological practice.The dissertation uses ideas and methodological tools from the philosophy of mind and language, the philosophy of science, the history of science, and the psychology of concepts. (shrink)

The paper describes the change from molecular genetics to postgenomic biology. It focuses on phenomena in the regulation of gene expression that provide a break with the central dogma, according to which sequence specificity for a gene product must be template derived. In its place we find what is called here ‘constitutive molecular epigenesis’. Its three classes of phenomena, which I call sequence ‘activation’, ‘selection’ and ‘creation’, are exemplified by processes such as transcriptional activation, alternative cis- and trans-splicing, and RNA (...) editing. These phenomena support the following main theses of the paper: 1. Other molecular resources share the causal role of ‘genes’: the ‘causal specificity’ for the linear sequence of any gene product is distributed between the coding sequence, cis-acting sequences, trans-acting factors, environmental signals, and the contingent history of the cell (the cellular code) (thesis of distributed causal specificity). 2. These multiple and overlapping processing and targeting mechanisms amplify the repertoire of RNA and protein products specified through the eukaryotic genome, expanding the possibilities specified by the literal code of DNA (thesis of genetic underdeterminism). 3. These mechanisms of gene expression change the focus of postgenomic research from single molecules and their molecular, biochemical and intrinsic function to their cellular, constituent, component or contextual function due to their recruitment and organization in complex cellular networks. In other words, all agents involved in the regulation of gene expression, including DNA, must interact with other agents to achieve full specificity, which is imposed by regulated recruitment and combinatorial control (theses of regulated recruitment and of system analysis). I conclude from these three main theses that the complexity of higher organisms lies not in its number of genes but in the flexibility, versatility and reactivity of its whole genome. (shrink)

Current knowledge about the variety and complexity of the processes that allow regulated gene expression in living organisms calls for a new understanding of genes. A ‘postgenomic’ understanding of genes as entities constituted during genome expression is outlined and illustrated with specific examples that formed part of a survey research instrument developed by two of the authors for an ongoing empirical study of conceptual change in contemporary biology.