This chapter contains section titled: The Neutral Theory of Molecular Evolution The Molecular Clock The Neutral Null Model Controversy in Molecular Evolution Acknowledgment References Further Reading.

This paper focuses on the consolidation of Molecular Evolution, a field originating in the 1960s at the interface of molecular biology, biochemistry, evolutionary biology, biophysics and studies on the origin of life and exobiology. The claim is made that Molecular Evolution became a discipline by integrating different sorts of scientific traditions: experimental, theoretical and comparative. The author critically incorporates Timothy Lenoir’s treatment of disciplines , as well as ideas developed by Stephen Toulmin on the same (...) subject. On their account disciplines are spaces where the social and epistemic dimensions of science are deeply and complexly interwoven. However, a more detailed account of discipline formation and the dynamics of an emerging disciplinary field is lacking in their analysis. The present essay suggests focusing on the role of scientific concepts in the double configuration of disciplines: the social/political and the epistemic order. In the case of Molecular Evolution the concepts of molecular clock and informational molecules played a central role, both in differentiating molecular from classical evolutionists, and in promoting communication between the different sorts of traditions integrated in Molecular Evolution. The paper finishes with a reflection on the historicity of disciplines, and the historicity of our concepts of disciplines. (shrink)

The discoveries, advancements and continuing controversies in the field of molecular evolution are reviewed. Topics summarized are (1) the evolution of the genetic code, (2) gene evolution including the demonstration of homology, estimation of sequence divergence, phylogenetic trees, the molecular clock and the origin of genes and gene families by various genetic mechanisms, and (3) eukaryotic genome evolution, including the highly repeated satellite sequences, the interspersed and potentially mobile repeated sequences and the unique sequence (...) fraction of the genome. (shrink)

Adaptive immunity is unique to the vertebrates, and the molecules involved (including immunoglobulins, T cell receptors and the major histocompatibility complex molecules) seem to have diversified very rapidly early in vertebrate history. Reconstruction of gene phylogenies has yielded insights into the evolutionary origin of a number of molecular systems, including the complement system and the major histocompatibility complex (MHC). These analyses have indicated that the C5 component of complement arose by gene duplication prior to the divergence of C3 and (...) C4, which suggests that the alternative complement pathway was the first to evolve. In the case of the MHC, phylogenetic analysis supports the hypothesis that MHC class II molecules evolved before class I molecules. The fact that the MHC‐linked proteasome components that specifically produce peptides for presentation by class I MHC appear to have originated before the separation of jawed and jawless vertebrates suggests that the MHC itself may have been present at this time. Immmune system gene families have evolved by gene duplication, interlocus recombination and (in some cases) positive Darwinian selection favoring diversity at the amino acid level. (shrink)

Microscopy has revealed tremendous diversity of bacterial and eukaryotic forms. Recent molecular analyses show discordance in estimates of biodiversity between morphological and molecular analyses. Moreover, phylogenetic analyses of the diversity of microbial forms reveal evidence of convergence at scales as deep as interdomain: morphologies shared between bacteria and eukaryotes. Here, we highlight examples of such discordance, focusing on exemplary lineages such as testate amoebae, ciliates, and cyanobacteria. These have long histories of morphological study, enabling deeper analyses on both (...) the molecular and morphological sides. We discuss examples in two main categories: (i) morphologically identical (or highly similar) individuals that are genetically distinct and (ii) morphologically distinct individuals that are genetically the same. We argue that hypotheses about discordance can be tested using the concept of neutral morphologies, or more broadly neutral phenotypes, as a null hypothesis. -/- . (shrink)

It is proposed that early in phylogeny a large proportion of amino acid substitutions were selectively neutral, but that bursts of adaptive substitutions during major radiations of life so increased selective constraints that most mutations in modern proteins are detrimental. Recent findings on DNA nucleotide sequences indicate that decreasing mutation rates further slowed the rate of molecular evolution in the lineage to humans.

Biologists and historians often present natural history and molecular biology as distinct, perhaps conflicting, fields in biological research. Such accounts, although supported by abundant evidence, overlook important areas of overlap between these areas. Focusing upon examples drawn particularly from systematics and molecular evolution, I argue that naturalists and molecular biologists often share questions, methods, and forms of explanation. Acknowledging these interdisciplinary efforts provides a more balanced account of the development of biology during the post-World War II (...) era. (shrink)

This article describes a current view of the events that initiated the transition from the rich organic and inorganic chemistry of the primitive Earth to the earliest forms of life. It is a personal condensation of the basic ideas developed in the so‐called Göttingen school. Most of these will be found in the seminal paper of Eigen1 and the other sources cited. A detailed exposition is given by Küppers2.

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)

In this paper, I analyze George Gaylord Simpson's response to the molecularization of evolutionary biology from his unique perspective as a paleontologist. I do so by exploring his views on early attempts to reconstruct phylogenetic relationships among primates using molecular data. Particular attention is paid to Simpson's role in the evolutionary synthesis of the 1930s and 1940s, as well as his concerns about the rise of molecular biology as a powerful discipline and world-view in the 1960s. I argue (...) that Simpson's belief in the supremacy of natural selection as the primary driving force of evolution, as well as his view that biology was a historical science that seeks ultimate causes and highlights contingency, prevented him from acknowledging that the study of molecular evolution was an inherently valuable part of the life sciences. (shrink)

This article offers three contrasting cases of the use of neutrality and drift in molecular evolution. In the first, neutrality is assumed as a simplest case for modeling. In the second and third, concepts of drift and neutrality are developed within the context of population genetics testing and the development and application of the molecular clock.

ArgumentThis paper explores the connection between the epistemic and the “political” dimensions of the metaphor of information during the early days of the study of Molecular Evolution. While preserving some of the meanings already documented in the history of molecular biology, the metaphor acquired a new, powerful use as a substitute for “history.” A rhetorical analysis of Emilé Zuckerkandl's paper, “Molecules as Documents of Evolutionary History,” highlights the ways in which epistemic claims on the validity and superiority (...) of molecular evidence for evolution were intimately connected with authority issues in evolutionary biology. The debate is situated within the framework of the battle for resources between traditional evolutionists and molecular biologists at the beginning of the 1960s. The architects of evolutionary synthesis questioned the idea that molecular characters constitute “cleaner” and “more direct” evidence of evolution. Nevertheless, the information discourse constituted a productive space for the development of a new research program that, paradoxically, has made explicit the limitations of the information metaphor in reconstructing life's history. (shrink)

MacDonald and Kreitman (1991) propose a test of the neutral mutationrandom drift (NM-RD) hypothesis, the central claim of the neutral theory of molecular evolution. The test involves generating predictions from the NM-RD hypothesis about patterns of molecular substitutions. Alternative selection hypotheses predict that the data will deviate from the predictions of the NM-RD hypothesis in specifiable ways. To conduct the test Mac- Donald and Kreitman examine the evolutionary dynamics of the alcohol dehydrogenase (Adh) gene in three species (...) of Drosophila. The test compares the number of DNA sequence changes between species and within species. The number of DNA differences is an indicator of the evolutionary rate of the Adh gene. Based on the test they conclude that there is strong evidence for adaptive protein evolution at particular sites in the gene. Understanding the test requires some basic knowledge about molecular terms and the predictions of neutral theory. The two important terms are fixed differences and polymorphisms. These are determined by comparing DNA sequences made up of thousands of individual nucleotide sites. A site that is unchanged within a species but different from a related species counts as a fixed difference. These are mutations that occur in some common ancestor of the lineage such that all descendants inherit the change. A site that differs within a species counts as a polymorphism. Determining the number of fixed differences and polymorphisms requires placing 1 each individual gene sequence onto a phylogenetic tree. A coalescent tree charts the ancestral relationships for a set of individual gene sequences. Sequences sampled from within a species form a within-species tree. The common ancestors of each within-species tree form a between-species tree. A detected difference counts as a polymorphism or a fixed difference depending on where it occurs in the phylogenetic tree (cf. Table 1). The test uses the numbers of polymorphisms and fixed differences as indicators of evolutionary rates.. (shrink)

The historical reconstruction of the origins of the Neutral Theory of Molecular Evolution (NTME) has been seen purely as an extension of a long-held theoretical debate between the classical and balance schools of Population Genetics. In this perspective, the NTME is but a different interpretation of the then recently published data on high intrapopulation genetic variability. In this paper we try to show that this thesis is deficient and partially incorrect. We show that the sources for the construction (...) and development of the NTME are more varied than this traditional account. We support the Dietrich Historical Thesis, which is the view that different versions of the NTME (Kimura, and King and Jukes) show different kinds of experimental and theoretical support and coincide in recognizing the importance of the then new molecular experimental approach and of its comparative results in evolutionary biology. We stress this case to show the limits of the traditional approach in history and philosophy of science that emphasizes the theoretical activities of scientists and the theoretical characterization of disciplines. (shrink)

Spiders spin multiple types of silks that are renowned for their superb mechanical properties. Flagelliform silk, used in the capture spiral of an orb‐web, is one of the few silks characterized by both cDNA and genomic DNA data. This fibroin is composed of repeating ensembles of three types of amino acid sequence motifs. The predominant subrepeat, GPGGX, likely forms a β‐turn, and tandem arrays of these turns are thought to create β‐spirals. These spring‐like helices may be critical for the exceptional (...) ability of capture silk to stretch and recoil. Each ensemble of motifs was found to correspond to a different exon within the flagelliform gene. The pattern of sequence similarity among exons indicates intragenic concerted evolution. Surprisingly, the introns between the iterated exons are also homogenized with each other. This unusual molecular architecture in the flagelliform silk gene has implications for the evolution and maintenance of spider silk proteins. BioEssays 23:750–756, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The Segregation Distorter (SD) system of Drosophila melanogaster is one the best‐characterized meiotic drive complexes known. SD gains an unfair transmission advantage through heterozygous SD/SD+ males by incapacitating SD+‐bearing spermatids so that virtually all progeny inherit SD. Segregation distorter (Sd), the primary distorting locus in the SD complex, is a truncated duplication of the RanGAP gene, a major regulator of the small GTPase Ran, which has several functions including the maintenance of the nucleocytoplasmic RanGTP concentration gradient that mediates nuclear transport. (...) The truncated Sd‐RanGAP protein is enzymatically active but mislocalizes to the nucleus where it somehow causes distortion. Here I present data consistent with the idea that wild‐type RanGAP, and possibly other loci able to influence the RanGTP gradient, has been caught up in an ancient genetic conflict that predates the SD complex. The legacy of this conflict could include the unexpectedly rapid evolution of nuclear transport‐related proteins, the accumulation of chromosomal inversions, the recruitment of gene duplications, and the turnover of repetitive sequences in the centric heterochromatin. BioEssays 29:386–391, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

There is growing interest in the evolutionary dynamics of molecular genetic pathways and networks, and the extent to which the molecular evolution of a gene depends on its position within a pathway or network, as well as over‐all network topology. Investigations on the relationships between network organization, topological architecture and evolutionary dynamics provide intriguing hints as to how networks evolve. Recent studies also suggest that genetic pathway and network structures may influence the action of evolutionary forces, and (...) may play a role in maintaining phenotypic robustness in organisms. BioEssays 26:479–484, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

This paper extends previous arguments against the assumption that the study of variation at the molecular level was instigated with a view to solving an internal conflict between the balance and classical schools of population genetics. It does so by focusing on the intersection of basic research in protein chemistry and the molecular approach to disease with the enactment of global health campaigns during the Cold War period. The paper connects advances in research on protein structure and function (...) as reflected in Christian Anfinsen’s The molecular basis of evolution, with a political reading of Emilé Zuckerkandl and Linus Pauling’s identification of molecular disease and evolution. Beyond atomic fallout, these advances constituted a rationale for the promotion of genetic surveys of human populations in the Third World, in connection with international health programs. Light is shed not only on the experimental roots of the molecular challenge but on the broader geopolitical context where the rising role of biomedicine and public health had an impact on evolutionary biology. (shrink)

Molecular Weismannism is the claim that: “In the development of an individual, DNA causes the production both of DNA (genetic material) and of protein (somatic material). The reverse process never occurs. Protein is never a cause of DNA”. This principle underpins both the idea that genes are the objects upon which natural selection operates and the idea that traits can be divided into those that are genetic and those that are not. Recent work in developmental biology and in philosophy (...) of biology argues that an acceptance of Molecular Weismannism requires the tacit assumption that genetic causes are different in kind from other developmental causes. They argue that if this assumption proves to be unwarranted then we should abandon, not just gene selectionism and gene centred functional solutions to the units of selection problem, but also the very notion that there is any such thing as a “genetic trait”. A group of possible causal distinctions (proximity, ultimacy and specificity) are explored and found wanting. It is argued that an extended version of information theory, while not strong enough to support Molecular Weismannism, will support both the claim that traits can be divided into those that are genetic and those that are not as well as the claim that there is good reason to privilege genetic causes within evolutionary and developmental explanations. The outcome of this for the units of selection debate is explored. (shrink)

Recent advances in molecular biology and microanatomy have supported homologies of body parts between vertebrates and extant invertebrate chordates, thus providing insights into the body plan of the proximate ancestor of the vertebrates. For example, this ancestor probably had a relatively complex brain and a precursor of definitive neural crest. Additional insights into early vertebrate evolution have come from recent discoveries of Lower Cambrian soft body fossils of Haikouichthys and Myllokunmingia (almost certainly vertebrates, possibly related to modern lampreys) (...) and Yunnanozoon and Haikouella (evidently stem-group vertebrates). The earliest vertebrates had an unequivocally marine origin, probably evolved mineralised pharyngeal denticles before the dermal skeleton, and evidently utilised elastic recoil of the visceral arch skeleton for suction feeding. Moreover, the new data emphasise that the advent of definitive neural crest was supremely important for the evolutionary origin of the vertebrates. BioEssays 23:142–151, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

This paper argues that the “long 1970s” (1969–1983) is an important though often overlooked period in the development of a rich landscape in the research of metabolism, development, and evolution. The period is marked by: shrinking public funding of basic science, shifting research agendas in molecular biology, the incorporation of new phenomena and experimental tools from previous biological research at the molecular level, and the development of recombinant DNA techniques. Research was reoriented towards eukaryotic cells and development, (...) and in particular towards “giant” RNA processing and transcription. We will here focus on three different models of developmental regulation published in that period: the two models of eukaryotic genetic regulation at the transcriptional level that were developed by Georgii P. Georgiev on the one hand, and by Roy Britten and Eric Davidson on the other; and the model of genetic sufficiency and evolution of regulatory genes proposed by Emile Zuckerkandl. These three cases illustrate the range of exploratory hypotheses that characterised the challenging landscape of gene regulation in the 1970s, a period that in hindsight can be labelled as transitional, between the biology at the laboratory bench of the preceding period, and the biology of genetic engineering and intensive data-driven research that followed. (shrink)

English possessives with apostrophe mark.

Despite the transformation in biological practice and theory brought about by discoveries in molecular biology, until recently philosophy of biology continued to focus on evolutionary biology. When the Human Genome Project got underway in the late 1980s and early 1990s, philosophers of biology -- unlike historians and social scientists -- had little to add to the debate. In this landmark collection of essays, Sahotra Sarkar broadens the scope of current discussions of the philosophy of biology, viewing molecular biology (...) as a unifying perspective on life that complements that of evolutionary biology. His focus is on molecular biology, but the overriding question behind these papers is what molecular biology contributes to all traditional areas of biological research.Molecular biology -- described with some foresight in a 1938 Rockefeller Foundation report as a branch of science in which "delicate modern techniques are being used to investigate ever more minute details" -- and its modeling strategies apparently argue in favor of physical reductionism. Sarkar's first three chapters explore reductionism -- defending it, but cautioning that reduction to molecular interactions is not necessarily a reduction to genetics. The next sections of the book discuss function, exploring how functional explanations pose a problem for reductionism; the informational interpretation of biology and how it interacts with reductionism; and the tension between the unifying framework of molecular biology and the received framework of evolutionary theory. The concluding chapter is an essay in the emerging field of developmental evolution, exploring what molecular biology may contribute to the transformation of evolutionary theory as evolutionary theory takes into account morphogenetic development. (shrink)

Philosophical discussion of molecular and developmental biology began in the late 1960s with the use of genetics as a test case for models of theory reduction. With this exception, the theory of natural selection remained the main focus of philosophy of biology until the late 1970s. It was controversies in evolutionary theory over punctuated equilibrium and adaptationism that first led philosophers to examine the concept of developmental constraint. Developmental biology also gained in prominence in the 1980s as part of (...) a broader interest in the new sciences of self-organization and complexity. The current literature in the philosophy of molecular and developmental biology has grown out of these earlier discussions under the influence of twenty years of rapid and exciting growth of empirical knowledge. Philosophers have examined the concepts of genetic information and genetic program, competing definitions of the gene itself and competing accounts of the role of the gene as a developmental cause. The debate over the relationship between development and evolution has been enriched by theories and results from the new field of 'evolutionary developmental biology'. Future developments seem likely to include an exchange of ideas with the philosophy of psychology, where debates over the concept of innateness have created an interest in genetics and development. (shrink)

Evolutionary theory assumed that mutations occur constantly, gradually, and randomly over time. This formulation from the “modern synthesis” of the 1930s was embraced decades before molecular understanding of genes or mutations. Since then, our labs and others have elucidated mutation mechanisms activated by stress responses. Stress‐induced mutation mechanisms produce mutations, potentially accelerating evolution, specifically when cells are maladapted to their environment, that is, when they are stressed. The mechanisms of stress‐induced mutation that are being revealed experimentally in laboratory (...) settings provide compelling models for mutagenesis that propels pathogen–host adaptation, antibiotic resistance, cancer progression and resistance, and perhaps much of evolution generally. We discuss double‐strand‐break‐dependent stress‐induced mutation in Escherichia coli. Recent results illustrate how a stress response activates mutagenesis and demonstrate this mechanism's generality and importance to spontaneous mutation. New data also suggest a possible harmony between previous, apparently opposed, models for the molecular mechanism. They additionally strengthen the case for anti‐evolvability therapeutics for infectious disease and cancer. (shrink)

An exploration of the nexus between ecology, evolutionary biology and molecular biology, via the concept of phenotypic plasticity.