Testing hypotheses in macroevolution

Experimental manipulation of microevolution (changes in frequency of heritable traits in populations) has shed much light on evolutionary processes. But many evolutionary processes occur on scales that are not amenable to experimental manipulation. Indeed, one of the reasons that macroevolution (changes in biodiversity over time, space and lineages) has sometimes been a controversial topic is that processes underlying the generation of biological diversity generally operate at scales that are not open to direct observation or manipulation. Macroevolutionary hypotheses can be tested by using them to generate predictions then asking whether observations from the biological world match those predictions. Each study that identifies significant correlations between evolutionary events, processes or outcomes can generate new predictions that can be further tested with different datasets, allowing a cumulative process that may narrow down on plausible explanations, or lead to rejection of other explanations as inconsistent or unsupported. A similar approach can be taken even for unique events, for example by comparing patterns in different regions, lineages, or time periods. I will illustrate the promise and pitfalls of these approaches using a range of examples, and discuss the problems of inferring causality from significant evolutionary associations.     

Integrating mechanistic explanations through epistemic perspectives

Talk of levels is ubiquitous in philosophy, especially in the context of mechanistic explanations spanning multiple levels. The mechanistic conception of levels, however, does not allow for the kind of integration needed to construct such multi-level mechanistic explanations integrating observations from different scientific domains. To address the issues arising in this context, I build on a certain perspectival aspect inherent in the mechanistic view. Rather than focusing on compositionally related levels of mechanisms, I suggest analyzing the situation in terms of epistemic perspectives researchers take when making scientific observations. Characterizing epistemic perspectives along five dimensions allows for a systematic analysis of the relations the scientific observations made from these different epistemic perspectives. This, in turn, provides a solid foundation for integrating the mechanistic explanations that are based on the scientific observations in question.     

The naturalism of the sciences

The sciences are characterized by what is sometimes called a “methodological naturalism,” which disregards talk of divine agency. In response to those who argue that this reflects a dogmatic materialism, a number of philosophers have offered a pragmatic defense. The naturalism of the sciences, they argue, is provisional and defeasible: it is justified by the fact that unsuccessful theistic explanations have been superseded by successful natural ones. But this defense is inconsistent with the history of the sciences. The sciences have always exhibited what we call a domain naturalism. They have never invoked divine agency, but have always focused on the causal structure of the natural world. It is not the case, therefore, that the sciences once employed theistic explanations and then abandoned them. The naturalism of the sciences is as old as science itself.     

The role of key residues in structure, function, and stability of cytochrome-c

Cytochrome-c (cyt-c), a multi-functional protein, plays a significant role in the electron transport chain, and thus is indispensable in the energy-production process. Besides being an important component in apoptosis, it detoxifies reactive oxygen species. Two hundred and eighty-five complete amino acid sequences of cyt-c from different species are known. Sequence analysis suggests that the number of amino acid residues in most mitochondrial cyts-c is in the range 104?±?10, and amino acid residues at only few positions are highly conserved throughout evolution. These highly conserved residues are Cys14, Cys17, His18, Gly29, Pro30, Gly41, Asn52, Trp59, Tyr67, Leu68, Pro71, Pro76, Thr78, Met80, and Phe82. These are also known as “key residues”, which contribute significantly to the structure, function, folding, and stability of cyt-c. The three-dimensional structure of cyt-c from ten eukaryotic species have been determined using X-ray diffraction studies. Structure analysis suggests that the tertiary structure of cyt-c is almost preserved along the evolutionary scale. Furthermore, residues of N/C-terminal helices Gly6, Phe10, Leu94, and Tyr97 interact with each other in a specific manner, forming an evolutionary conserved interface. To understand the role of evolutionary conserved residues on structure, stability, and function, numerous studies have been performed in which these residues were substituted with different amino acids. In these studies, structure deals with the effect of mutation on secondary and tertiary structure measured by spectroscopic techniques; stability deals with the effect of mutation on T _m (midpoint of heat denaturation), ?G _D (Gibbs free energy change on denaturation) and folding; and function deals with the effect of mutation on electron transport, apoptosis, cell growth, and protein expression. In this review, we have compiled all these studies at one place. This compilation will be useful to biochemists and biophysicists interested in understanding the importance of conservation of certain residues throughout the evolution in preserving the structure, function, and stability in proteins.     

Essentially narrative explanations

This essay argues that narrative explanations prove uniquely suited to answering certain explanatory questions, and offers reasons why recognizing a type of statement that requires narrative explanations crucially informs on their assessment. My explication of narrative explanation begins by identifying two interrelated sources of philosophical unhappiness with them. The first I term the problem of logical formlessness and the second the problem of evaluative intractability. With regard to the first, narratives simply do not appear to instantiate any logical form recognized as inference licensing. But absent a means of identifying inferential links, what justifies connecting explanans and explanandum? Evaluative intractability, the second problem, thus seems a direct consequence. This essay shows exactly why these complaints prove unfounded by explicating narrative explanations in the process of answering three interrelated questions. First, what determines that an explanation has in some critical or essential respect a narrative form? Second, how does a narrative in such cases come to constitute a plausible explanation? Third, how do the first two considerations yield a basis for evaluating an explanation offered as a narrative? Answers to each of these questions include illustrations of actual narrative explanations and also function to underline attendant dimensions of evaluation.     

Drawing the line between kinematics and dynamics in special relativity

Special relativity is preferable to those parts of Lorentz's classical ether theory it replaced because it shows that various phenomena that were given a dynamical explanation in Lorentz's theory are actually kinematical. In his book, Physical Relativity, Harvey Brown challenges this orthodox view. I defend it. The phenomena usually discussed in this context in the philosophical literature are length contraction and time dilation. I consider three other phenomena in the same class, each of which played a role in the early reception of special relativity in the physics literature: the Fresnel drag effect, the velocity dependence of electron mass, and the torques on a moving capacitor in the Trouton–Noble experiment. I offer historical sketches of how Lorentz's dynamical explanations of these phenomena came to be replaced by their now standard kinematical explanations. I then take up the philosophical challenge posed by the work of Harvey Brown and Oliver Pooley and clarify how those kinematical explanations work. In the process, I draw attention to the broader importance of the kinematics–dynamics distinction.     

Hobbes on natural philosophy as “True Physics” and mixed mathematics

In this paper, I offer an alternative account of the relationship of Hobbesian geometry to natural philosophy by arguing that mixed mathematics provided Hobbes with a model for thinking about it. In mixed mathematics, one may borrow causal principles from one science and use them in another science without there being a deductive relationship between those two sciences. Natural philosophy for Hobbes is mixed because an explanation may combine observations from experience (the ‘that’) with causal principles from geometry (the ‘why’). My argument shows that Hobbesian natural philosophy relies upon suppositions that bodies plausibly behave according to these borrowed causal principles from geometry, acknowledging that bodies in the world may not actually behave this way. First, I consider Hobbes's relation to Aristotelian mixed mathematics and to Isaac Barrow's broadening of mixed mathematics in Mathematical Lectures (1683). I show that for Hobbes maker's knowledge from geometry provides the ‘why’ in mixed-mathematical explanations. Next, I examine two explanations from De corpore Part IV: (1) the explanation of sense in De corpore 25.1-2; and (2) the explanation of the swelling of parts of the body when they become warm in De corpore 27.3. In both explanations, I show Hobbes borrowing and citing geometrical principles and mixing these principles with appeals to experience.     

Re-orienting discussions of scientific explanation: A functional perspective

Philosophy of science offers a rich lineage of analysis concerning the nature of scientific explanation, but the vast majority of this work, aiming to provide an analysis of the relation that binds a given explanans to its corresponding explanandum, presumes the proper analytic focus rests at the level of individual explanations. There are, however, other questions we could ask about explanation in science, such as: What role(s) does explanatory practice play in science? Shifting focus away from explanations, as achievements, toward explaining, as a coordinated activity of communities, the functional perspective aims to reveal how the practice of explanatory discourse functions within scientific communities given their more comprehensive aims and practices. In this paper, I outline the functional perspective, argue that taking the functional perspective can reveal important methodological roles for explanation in science, and consequently, that beginning here provides resources for developing more adequate responses to traditional concerns. In particular, through an examination of the ideal gas law, I emphasize the normative status of explanations within scientific communities and discuss how such status underwrites a compelling rationale for explanatory power as a theoretical virtue.     

Where explanation ends: Understanding as the place the spade turns in the social sciences

Explanations implicitly end with something that makes sense, and begin with something that does not make sense. A statistical relationship, for example, a numerical fact, does not make sense; an explanation of this relationship adds something, such as causal information, which does make sense, and provides an endpoint for the sense-making process. Does social science differ from natural science in this respect? One difference is that in the natural sciences, models are what need “understanding.” In the social sciences, matters are more complex. There are models, such as causal models, which need to be understood, but also depend on background knowledge that goes beyond the model and the correlations that make it up, which produces a regress. The background knowledge is knowledge of in-filling mechanisms, which are normally made up of elements that involve the direct understanding of the acting and believing subjects themselves. These models, and social science explanations generally, are satisfactory only when they end the regress in this kind of understanding or use direct understanding evidence to decide between alternative mechanism explanations.     

The directionality of distinctively mathematical explanations

In “What Makes a Scientific Explanation Distinctively Mathematical?” (2013b), Lange uses several compelling examples to argue that certain explanations for natural phenomena appeal primarily to mathematical, rather than natural, facts. In such explanations, the core explanatory facts are modally stronger than facts about causation, regularity, and other natural relations. We show that Lange's account of distinctively mathematical explanation is flawed in that it fails to account for the implicit directionality in each of his examples. This inadequacy is remediable in each case by appeal to ontic facts that account for why the explanation is acceptable in one direction and unacceptable in the other direction. The mathematics involved in these examples cannot play this crucial normative role. While Lange's examples fail to demonstrate the existence of distinctively mathematical explanations, they help to emphasize that many superficially natural scientific explanations rely for their explanatory force on relations of stronger-than-natural necessity. These are not opposing kinds of scientific explanations; they are different aspects of scientific explanation.     

Isolating <Emphasis Type="Italic">Escherichia coli</Emphasis> strains for recombinant protein production

Escherichia coli has been widely used for the production of recombinant proteins. To improve protein production yields in E. coli, directed engineering approaches have been commonly used. However, there are only few reported examples of the isolation of E. coli protein production strains using evolutionary approaches. Here, we first give an introduction to bacterial evolution and mutagenesis to set the stage for discussing how so far selection- and screening-based approaches have been used to isolate E. coli protein production strains. Finally, we discuss how evolutionary approaches may be used in the future to isolate E. coli strains with improved protein production characteristics.     

Saving the mutual manipulability account of constitutive relevance

Constitutive mechanistic explanations are said to refer to mechanisms that constitute the phenomenon-to-be-explained. The most prominent approach of how to understand this relation is Carl Craver's mutual manipulability approach (MM) to constitutive relevance. Recently, MM has come under attack (Baumgartner and Casini 2017; Baumgartner and Gebharter 2015; Harinen 2014; Kästner 2017; Leuridan 2012; Romero 2015). It is argued that MM is inconsistent because, roughly, it is spelled out in terms of interventionism (which is an approach to causation), whereas constitutive relevance is said to be a non-causal relation. In this paper, I will discuss a strategy of how to resolve this inconsistency—so-called fat-handedness approaches (Baumgartner and Casini 2017; Baumgartner and Gebharter 2015; Romero 2015). I will argue that these approaches are problematic. I will present a novel suggestion for how to consistently define constitutive relevance in terms of interventionism. My approach is based on a causal interpretation of manipulability in terms of causal relations between the mechanism's components and what I will call temporal EIO-parts of the phenomenon. Still, this interpretation accounts for the fundamental difference between constitutive relevance and causal relevance.     

Galton's Quincunx: Probabilistic causation in developmental behavior genetics

In what sense are associations between particular markers and complex behaviors made by genome-wide association studies (GWAS) and related techniques discoveries of, or entries into the study of, the causes of those behaviors? In this paper, we argue that when applied to individuals, the kinds of probabilistic ‘causes’ of complex traits that GWAS-style studies can point towards do not provide the kind of causal information that is useful for generating explanations; they do not, in other words, point towards useful explanations of why particular individuals have the traits that they do. We develop an analogy centered around Galton's “Quincunx” machine; while each pin might be associated with outcomes of a certain sort, in any particular trial, that pin might be entirely bypassed even if the ball eventually comes to rest in the box most strongly associated with that pin. Indeed, in any particular trial, the actual outcome of a ball hitting a pin might be the opposite of what is usually expected. While we might find particular pins associated with outcomes in the aggregate, these associations will not provide causally relevant information for understanding individual outcomes. In a similar way, the complexities of development likely render impossible any moves from population-level statistical associations between genetic markers and complex behaviors to an understanding of the causal processes by which individuals come to have the traits that they in fact have.     

Differential evolution of signal-responsive RNA elements and upstream factors that control alternative splicing

Cell signal-regulated alternative splicing occurs for many genes but the evolutionary origin of the regulatory components and their relationship remain unclear. This review focuses on the alternative splicing components of several systems based on the available bioinformatics data. Eight mammalian RNA elements for signal-regulated splicing were aligned among corresponding sequences from dozens of representative vertebrate species to allow for assessment of the trends in evolutionary changes. Four distinct trends were observed. Four of the elements are highly conserved in bird, reptile and fish species examined (i); two elements can be found in fish but the sequences have been changing till in marsupials or higher mammals (ii); one element is almost exclusively found in mammals with mostly the same sequence (iii); and one element can be found in birds or lower vertebrates but expanded abruptly to have variable numbers of copies in mammals (iv). All examined prototype trans-acting factors and protein kinases emerged earlier than the RNA elements but additional (paralog) factors emerged in the same or later species. Thus, after their emergence mainly in fish or mammals with pre-existing prototype trans-acting factors/kinases, half of the elements have been highly conserved from fish to humans but the other half have evolved differentially with additional trans-acting factors. Their differential evolution likely contributes to the exon- and species/class-specific control of alternative splicing and its regulation by cell signals. The evolvement of a group of mammal-specific components would help relay signals from extracellular stimuli to the splicing machinery and thus contribute to higher proteomic diversity.     

The functional bias of the dual nature of technical artefacts program

In 2006, in a special issue of this journal, several authors explored what they called the dual nature of artefacts. The core idea is simple, but attractive: to make sense of an artefact, one needs to consider both its physical nature—its being a material object—and its intentional nature—its being an entity designed to further human ends and needs. The authors construe the intentional component quite narrowly, though: it just refers to the artefact’s function, its being a means to realize a certain practical end. Although such strong focus on functions is quite natural (and quite common in the analytic literature on artefacts), I argue in this paper that an artefact’s intentional nature is not exhausted by functional considerations. Many non-functional properties of artefacts—such as their marketability and ease of manufacture—testify to the intentions of their users/designers; and I show that if these sorts of considerations are included, one gets much more satisfactory explanations of artefacts, their design, and normativity.     

Realizability and the varieties of explanation

What realization is has been convincingly presented in relation to the way we determine what counts as the realizers of realized properties. The way we explain a fact of realization includes a reference to what realization should be; therefore it informs in turn our understanding of the nature of realization. Conceptions of explanation are thereby included in the views of realization as a metaphysical property.Recently, several major views of realization such as Polger and Shapiro's or Gillett and Aizawa's, however competing, have relied on the neo-mechanicist theory of explanations (e.g,. Darden and Caver 2013), currently popular among philosophers of science. However, it has also been increasingly argued that some explanations are not mechanistic (e.g., Batterman 2009).Using an account given in Huneman (2017), I argue that within those explanations the fact that some mathematical properties are instantiated is explanatory, and that this defines a specific explanatory type called “structural explanation”, whose subtypes could be: optimality explanations (usually found in economics), topological explanations, etc. This paper thereby argues that all subtypes of structural explanation define several kinds of realizability, which are not equivalent to the usual notion of realization tied to mechanistic explanations, onto which many of the philosophical investigations are focused. Then it draws some consequences concerning the notion of multiple realizability.     

The unfolding of the historical style in modern cosmology: Emergence,evolution, entrenchment

This paper traces the emergence, evolution and subsequent entrenchment of the historical style in the shifting scene of modern cosmological inquiry. It argues that the historical style in cosmology was forged in the early decades of the 20^th century and continued to evolve in the century that followed. Over time, the scene of cosmological inquiry has gradually become dominated and entirely constituted by historicist explanations. Practices such as forwards and backwards temporal extrapolation (thinking about the past evolutionary history of the universe with different initial conditions and other parameters) are now commonplace. The non-static geometrization of the cosmos in the early 20th century led to inquires thinking about the cosmos in evolutionary terms. Drawing on the historical approach of Gamow (and contrasting this with the ahistorical approach of Bondi), the paper then argues that the historical style became a major force as inquirers began scouring the universe for fossils and other relics as a new form of scientific practice—cosmic palaeontology. By the 1970s the historical style became the bedrock of the discipline and the presupposition of new lines of inquiry. By the end of the 20th century, the historical style was pushed to its very limits as temporal reasoning began to occur beyond a linear historical narrative. With the atemporal ‘ensemble’ type multiverse proposals, a certain type of ahistorical reasoning has been reintroduced to cosmological discourse, which, in a sense, represents a radical de-historicization of the historical style in cosmology. Some are now even attempting to explain the laws of physics in terms of their historicity.     

Recent advances in the biosynthesis of modified tetrapyrroles: the discovery of an alternative pathway for the formation of heme and heme d 1

Hemes (a, b, c, and o) and heme d ₁ belong to the group of modified tetrapyrroles, which also includes chlorophylls, cobalamins, coenzyme F₄₃₀, and siroheme. These compounds are found throughout all domains of life and are involved in a variety of essential biological processes ranging from photosynthesis to methanogenesis. The biosynthesis of heme b has been well studied in many organisms, but in sulfate-reducing bacteria and archaea, the pathway has remained a mystery, as many of the enzymes involved in these characterized steps are absent. The heme pathway in most organisms proceeds from the cyclic precursor of all modified tetrapyrroles uroporphyrinogen III, to coproporphyrinogen III, which is followed by oxidation of the ring and finally iron insertion. Sulfate-reducing bacteria and some archaea lack the genetic information necessary to convert uroporphyrinogen III to heme along the “classical” route and instead use an “alternative” pathway. Biosynthesis of the isobacteriochlorin heme d ₁, a cofactor of the dissimilatory nitrite reductase cytochrome cd ₁, has also been a subject of much research, although the biosynthetic pathway and its intermediates have evaded discovery for quite some time. This review focuses on the recent advances in the understanding of these two pathways and their surprisingly close relationship via the unlikely intermediate siroheme, which is also a cofactor of sulfite and nitrite reductases in many organisms. The evolutionary questions raised by this discovery will also be discussed along with the potential regulation required by organisms with overlapping tetrapyrrole biosynthesis pathways.     

Collaborative explanation and biological mechanisms

This paper motivates and outlines a new account of scientific explanation, which I term ‘collaborative explanation.’ My approach is pluralist: I do not claim that all scientific explanations are collaborative, but only that some important scientific explanations are—notably those of complex organic processes like development. Collaborative explanation is closely related to what philosophers of biology term ‘mechanistic explanation’ (e.g., Machamer et al., Craver, 2007). I begin with minimal conditions for mechanisms: complexity, causality, and multilevel structure. Different accounts of mechanistic explanation interpret and prioritize these conditions in different ways. This framework reveals two distinct varieties of mechanistic explanation: causal and constitutive. The two have heretofore been conflated, with philosophical discussion focusing on the former. This paper addresses the imbalance, using a case study of modeling practices in Systems Biology to reveals key features of constitutive mechanistic explanation. I then propose an analysis of this variety of mechanistic explanation, in terms of collaborative concepts, and sketch the outlines of a general theory of collaborative explanation. I conclude with some reflections on the connection between this variety of explanation and social aspects of scientific practice.