The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology ‘revolutionizes’ molecular biology and ‘transcends’ its (...) assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology’s use of modelling and bioinformatics, and by its scale enlargement. (shrink)

It is becoming increasingly evident that the driving forces of evolutionary novelty are not randomly derived chance mutations of the genetic text, but a precise genome editing by omnipresent viral agents. These competences integrate the whole toolbox of natural genetic engineering, replication, transcription, translation, genomic imprinting, genomic creativity, enzymatic inventions and all types of genetic repair patterns. Even the non-coding, repetitive DNA sequences which were interpreted as being ancient remnants of former evolutionary stages are now recognized as being of viral (...) descent and crucial for higher-order regulatory and constitutional functions of protein structural vocabulary. In this article I argue that non-randomly derived natural genome editing can be envisioned as (a) combinatorial (syntactic), (b) context-specific (pragmatic) and (c) content-sensitive (semantic) competences of viral agents. These three-leveled biosemiotic competences could explain the emergence of complex new phenotypes in single evolutionary events. After short descriptions of the non-coding regulatory networks, major viral life strategies and pre-cellular viral life three of the major steps in evolution serve as examples: There is growing evidence that natural genome-editing competences of viruses are essential (1) for the evolution of the eukaryotic nucleus, (2) the adaptive immune system and (3) the placental mammals. (shrink)

Essentialism is widely regarded as a mistaken view of biological kinds, such as species. After recounting why (sections 2-3), we provide a brief survey of the chief responses to the “death of essentialism” in the philosophy of biology (section 4). We then develop one of these responses, the claim that biological kinds are homeostatic property clusters (sections 5-6) illustrating this view with several novel examples (section 7). Although this view was first expressed 20 years ago, and has received recent discussion (...) and critique, it remains underdeveloped and is often misrepresented by its critics (section 8). (shrink)

Philosophical discussions of biological classification have failed to recognise the central role of homology in the classification of biological parts and processes. One reason for this is a misunderstanding of the relationship between judgments of homology and the core explanatory theories of biology. The textbook characterisation of homology as identity by descent is commonly regarded as a definition. I suggest instead that it is one of several attempts to explain the phenomena of homology. Twenty years ago the ‘new experimentalist’ movement (...) in philosophy of science drew attention to the fact that many experimental phenomena have a ‘life of their own’: the conviction that they are real is not dependent on the theories used to characterise and explain them. I suggest that something similar can be true of descriptive phenomena, and that many homologies are phenomena of this kind. As a result the descriptive biology of form and function has a life of its own—a degree of epistemological independence from the theories that explain form and function. I also suggest that the two major ‘homology concepts’ in contemporary biology, usually seen as two competing definitions, are in reality complementary elements of the biological explanation of homology. (shrink)

The human genome project's lasting legacies are the emerging insights into human physiology and disease, and the ascendance of biology as the dominant science of the 21st century. Sequencing revealed that >90% of the human genome is not coding for proteins, as originally thought, but rather is overwhelmingly transcribed into non‐protein coding, or non‐coding, RNAs (ncRNAs). This discovery initially led to the hypothesis that most genomic DNA is “junk”, a term still championed by some geneticists and evolutionary biologists. In contrast, (...) molecular biologists and biochemists studying the vast number of transcripts produced from most of this genome “junk” often surmise that these ncRNAs have biological significance. What gives? This essay contrasts the two opposing, extant viewpoints, aiming to explain their bases, which arise from distinct reference frames of the underlying scientific disciplines. Finally, it aims to reconcile these divergent mindsets in hopes of stimulating synergy between scientific fields. (shrink)

Thomas Kuhn described the progress of science as comprising occasional paradigm shifts separated by interludes of ‘normal science’. The paradigm that has held sway since the inception of molecular biology is that genes (mainly) encode proteins. In parallel, theoreticians posited that mutation is random, inferred that most of the genome in complex organisms is non‐functional, and asserted that somatic information is not communicated to the germline. However, many anomalies appeared, particularly in plants and animals: the strange genetic phenomena of paramutation (...) and transvection; introns; repetitive sequences; a complex epigenome; lack of scaling of (protein‐coding) genes and increase in ‘noncoding’ sequences with developmental complexity; genetic loci termed ‘enhancers’ that control spatiotemporal gene expression patterns during development; and a plethora of ‘intergenic’, overlapping, antisense and intronic transcripts. These observations suggest that the original conception of genetic information was deficient and that most genes in complex organisms specify regulatory RNAs, some of which convey intergenerational information. Also see the video abstract here: https://youtu.be/qxeGwahBANw. (shrink)

Denis Nobel looks at four important misinterpretations of molecular biology concerning evolutionary processes and demonstrates that the new synthesis today looks rather outdated. The modern synthesis is nearly 80 years old. The proponents who worked out the modern synthesis had no access to the current knowledge on cell biology, genetics, epigenetics, RNA biology and virology. Therefore this contribution adds several aspects which Nobel’s article does not explicitly mention, providing some examples for a better understanding of evolutionary novelty.

Identification of non-coding RNAs (ncRNAs) has been significantly enhanced due to the rapid advancement in sequencing technologies. On the other hand, semantic annotation of ncRNA data lag behind their identification, and there is a great need to effectively integrate discovery from relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a precisely defined ncRNA controlled vocabulary, which can fill a specific and highly needed niche in unification of ncRNA biology.

It has long been thought that gene expression is tightly regulated in multicellular eukaryotes, so that expression profiles match functional profiles. This conception emerged from the assumption that gene activity is synonymous with gene function. This paradigm was first challenged by comparative protein electrophoresis studies showing extensive differences in expression patterns among related species. The paradigm is now being challenged by evolutionary transcriptomics using microarray technologies. Most gene expression profiles display features that lack any obvious functional significance. The so‐called “ectopic” (...) expression refers to the expression of genes at times and locations where the target gene is not known to have a function. However, ectopic expression might be associated with genuine function even if this function is not essential or has yet to be ascertained. Alternatively, ectopic expression might come about as a superfluous by‐product of regulatory systems, which would call for a revision of prevailing ideas about the specificity of gene regulation. We herein review available evidence for ectopic expression and the hypotheses proposed for its origin and evolution. We propose that ectopic expression must be regarded as part of an integrated phenotypic whole. It seems likely that ectopic expression represents a leak in the evolution of regulatory systems, but one that is endowed with considerable evolutionary possibilities. BioEssays 27:592–601, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

‘Information’ and ‘code’ originated as technical terms within linguistics and information theory but are now widely used in genetics and developmental biology. Against this background, it is examined if coded information distinguishes genes from other information carriers, i.e., whether there are genetic words or sentences by virtue of the genetic code, and, if so, whether they have any semantic content. It is concluded that there is no genetic language with semantic content, but that the genetic code still enables unique language-like (...) modes of transmission and interpretation of causal information. (shrink)

This two-part article presents the research program for a theory and empirical analysis of religious evolution. It is assumed that religion isprimarilya co-evolution to societal evolution, which in turn is a co-evolution to mental, organic, and physical evolution. The theory of evolution is triangulated with the systems theory and the semiotically informed theory of communication, so that knowledge can be gained that would not be acquired by only one of the three theories: The differentiation between religion and its environment can (...) be reconstructed based on the theory of evolution. The elements of the theory of evolution can be understood as the formation of systems. The semiotically informed theory of communication clarifies the conditions of the combination of both the systems theory and the theory of evolution as well as its objects. In turn, the combination of the systems theory and the theory of evolution can describe how communication—including religion and science—evolves and is structured. (shrink)

The discussion presents a framework of concepts that is intended to account for the rationality of semantic change and variation, suggesting 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 components, and that change in the concept’s inferential role and reference can be accounted for as being rational relative (...) to the third component, the concept’s epistemic goal. This framework is illustrated and defended by application to the history of the gene concept. It is explained how the molecular gene concept grew rationally out of the classical gene concept despite a change in reference, and why the use and reference of the contemporary molecular gene concept may legitimately vary from context to context. (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.

Radically new or unexpected findings in a science demand an openness to new concepts and styles of explanation. The time is more than ripe for asking ourselves what we have learned from the research program of comparative genomics. Where not long ago the human genome was expected to reveal a close association of complexity with the quantitative expansion of the roster of unique genes, more recent findings, especially in relation to comparisons between human and chimp, have raised the bracing possibility (...) that when it comes to complexity, it may be that `less is more'. But `less is more' is not the only observation or inference that follows from the data. The idea of `progressive detachment' will be introduced and set forth as the most perspicuous conceptual resource for unifying and interpreting the overall findings from comparative genomics to date. (shrink)

The Serial Endosymbiotic Theory explains the origin of nucleated eukaryotic cells by a merging of archaebacterial and eubacterial cells. The paradigmatic change is that the driving force behind evolution is not ramification but merging. Lynn Margulis describes the symbiogenetic processes in the language of mechanistic biology in such terms as “merging”, “fusion”, and “incorporation”. Biosemiotics argues that all cell-cell interactions are (rule-governed) sign-mediated interactions, i.e., communication processes. As the description of plant communication demonstrates, the biosemiotic approach is not limited to (...) the level of molecular biology, but is also helpful in examining all sign-mediated interactions between organisms on the phenotypic level. If biosemiotics also uses the notions of “language” and “communication” to describe non-human sign-mediated interactions, then the underlying scientific justification of such usage should be critically considered. Therefore, I summarize the history of this discussion held between 1920 and 1980 and present its result, the pragmatic turn. (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)

Within the last decade, thousands of studies have described communication processes in and between organisms. Pragmatic philosophy of biology views communication processes as rule-governed sign-mediated interactions (rsi's). As sign-using individuals exhibit a relationship to following or not-following these rules, the rsi's of living individuals dier fundamentally from cause-and-effect reactions with and between non-living matter, which exclusively underlie natural laws. Umwelt thus becomes a term in investigating physiological influences on organisms that are not components of rsi's. Mitwelt is a term for (...) the investigation of all rsi's of organisms. Living organisms are never solus ipse subjects of semioses, but share common sets of rules and signs. Life depends decisively on symbiotic communities. Serial Endosymbiotic Theory proved that the evolution of the eukaryotic super-kingdom was a merger of anchestral bacteria. The integration of bacterial genomes into eukaryotic genomes was also a step from analog to symbolic genetic codes. Now we know, that so-called ‘junk DNA’ has higher order regulatory functions on genome architecture and protein coding DNA plays only the role of a structural vocabulary. (shrink)

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)

The discovery and ongoing investigation of microRNAs suggest important conceptual and methodological lessons for philosophers and historians of biology. This paper provides an account of miRNA research and the shift from viewing these tiny regulatory entities as minor curiosities to seeing them as major players in the post-transcriptional regulation of genes. Conceptually, the study of miRNAs is part of a broader change in understandings of genetic regulation, in which simple switch-like mechanisms were reinterpreted as aspects of complex cellular and genome-wide (...) processes. Among them are the activities of small RNAs, previously regarded as non-functional. Methodologically, the miRNA story suggests new ways of characterizing biological research that should prove helpful to philosophers of science who seek to develop more pluralistic, pragmatic models of scientific inquiry. miRNA research displays iterative movements between multiple modes of investigation that include not only the proposal and testing of hypotheses but also exploratory, technology-oriented and question-driven modes of research. As an exemplary story of scientific discovery and development, the miRNA case illustrates transitions from genetics to genomics and systems biology, and it shows how diverse configurations of research practice are related to major scientific advances. (shrink)

The combination of evolutionary with engineering principles will enhance synthetic biology. Conversely, synthetic biology has the potential to enrich evolutionary biology by explaining why some adaptive space is empty, on Earth or elsewhere. Synthetic biology, the design and construction of artificial biological systems, substitutes bio‐engineering for evolution, which is seen as an obstacle. But because evolution has produced the complexity and diversity of life, it provides a proven toolkit of genetic materials and principles available to synthetic biology. Evolution operates on (...) the population level, with the populations composed of unique individuals that are historical entities. The source of genetic novelty includes mutation, gene regulation, sex, symbiosis, and interspecies gene transfer. At a phenotypic level, variation derives from regulatory control, replication and diversification of components, compartmentalization, sexual selection and speciation, among others. Variation is limited by physical constraints such as diffusion, and chemical constraints such as reaction rates and membrane fluidity. While some of these tools of evolution are currently in use in synthetic biology, all ought to be examined for utility. A hybrid approach of synthetic biology coupled with fine‐tuning through evolution is suggested. (shrink)

The largest transcriptome reported so far comprises 60,770 mouse full‐length cDNA clones, and is an effective reference data set for comparative transcriptomics. The number of mouse cDNAs identified greatly exceeds the number of genes predicted from the sequenced human and mouse genomes. This is largely because of extensive alternative splicing and the presence of many non‐coding RNAs (ncRNAs), which are difficult to predict from genomic sequences. Notably, ncRNAs are a major component of the transcriptomes of higher organisms, and many sense–antisense (...) pairs have been identified. The ncRNAs function in a range of regulatory mechanisms for gene expression and other biological processes. They might also have contributed to the increased functional diversification of genomes during evolution. In this review, we discuss aspects of the transcriptome of various organisms in relation to the mouse data, in order to shed light on the regulatory mechanisms and physiological significance of these abundant RNAs. BioEssays 26:833–843, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The special properties of the Y chromosome stem form the fact that it is a non‐recombining degenerate derivative of the X chromosome. The absence of homologous recombination between the X and the Y chromosome leads to gradual degeneration of various Y chromosome genes on an evolutionary timescale. The absence of recombination, however, also favors the accumulation of transposable elements on the Y chromosome during its evolution, as seen with both Drosophila and mammalian Y chromosomes. Alongside these processes, the acquisition and (...) amplification of autosomal male benefit genes occur. This review will focus on recent studies that reveal the autosome‐acquired genes on the Y chromosome of both Drosophila and humans. The evolution of the acquired and amplified genes on the Y chromosome is also discussed. Molecular and comparative analyses of Y‐linked repeats in the Drosophila melanogaster genome demonstrate that there was a period of their degeneration followed by a period of their integration into RNAi silencing, which was beneficial for male fertility. Finally, the function of non‐coding RNA produced by amplified Y chromosome genetic elements will be discussed. BioEssays 27:1256–1262, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Since its original identification as a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex, K protein has been found not only in the nucleus but also in the cytoplasm and mitochondria and is implicated in chromatin remodeling, transcription, splicing and translation processes. K protein contains multiple modules that, on one hand, bind kinases while, on the other hand, recruit chromatin, transcription, splicing and translation factors. Moreover, the K‐ protein‐mediated interactions are regulated by signaling cascades. These observations are consistent with K (...) protein acting as a docking platform to integrate signaling cascades by facilitating cross‐talk between kinases and factors that mediate nucleic‐acid‐directed processes. Comparison of K across species reveals that it is an essential factor in metazoans, but not in yeast. Although some of the K protein interactions and functions are conserved in eukaryotes from yeast to man, the mammalian protein seems to play a wider role. The greater diversity of mammalian K protein interactions and function may reflect gain of novel docking sites and expansion evolutionary of gene expression networks. BioEssays 26:629–638, 2004. © 2004 Wiley Periodicals, Inc. (shrink)