There is long-standing conflict between genealogical and developmental accounts of homology. This paper provides a general framework that shows that these accounts are compatible and clarifies precisely how they are related. According to this framework, understanding homology requires both an abstract genealogical account that unifies the application of the term to all types of characters used in phylogenetic systematics and locally enriched accounts that apply only to specific types of characters. The genealogical account serves this unifying role by (...) relying on abstract notions of ‘descent’ and ‘character’. As a result, it takes for granted the existence of such characters. This requires theoretical justification that is provided by enriched accounts, which incorporate the details by which characters are inherited. These enriched accounts apply to limited domains, providing the needed theoretical justification for recognizing characters within that domain. Though connected to the genealogical account of homology in this way, enriched accounts include phenomena that fall outside the scope of the genealogical account. They therefore overlap, but are not nested within, the genealogical account. Developmental accounts of homology are to be understood as enriched accounts of body part homology. Once they are seen in this light, the conflict with the genealogical account vanishes. It is only by understanding the fine conceptual structure undergirding the many uses of the term ‘homology’ that we can understand how these uses hang together. (shrink)

“Functional homology” appears regularly in different areas of biological research and yet it is apparently a contradiction in terms—homology concerns identity of structure regardless of form and function. I argue that despite this conceptual tension there is a legitimate conception of ‘homology of function’, which can be recovered by utilizing a distinction from pre-Darwinian physiology (use versus activity) to identify an appropriate meaning of ‘function’. This account is directly applicable to molecular developmental biology and shares a connection (...) to the theme of hierarchy in homology. I situate ‘homology of function’ within existing definitions and criteria for structural assessments of homology, and introduce a criterion of ‘organization’ for judging function homologues, which focuses on hierarchically interconnected interdependencies (similar to relative position and connection for skeletal elements in structural homology). This analysis of biological concepts has at least three broad philosophical consequences: (1) it provides the grounds for the study of behavior and psychological categories as homologues; (2) it demonstrates that philosophers who take selected effect function as primary effectively ignore large portions of comparative, structural, and experimental research, thereby misconstruing biological reasoning and knowledge; and, (3) it underwrites causal generalizations, which illuminates inferences made from model organisms in experimental biology. (shrink)

Homology is a natural kind term and a precise account of what homology is has to come out of theories about the role of homologues in evolution and development. Definitions of homology are discussed with respect to the question as to whether they are able to give a non-circular account of the correspondence or sameness referred to by homology. It is argued that standard accounts tie homology to operational criteria or specific research projects, but are (...) not yet able to offer a concept of homology that does not presuppose a version of homology or a comparable notion of sameness. This is the case for phylogenetic definitions that trace structures back to the common ancestor as well as for developmental approaches such as Wagner's biological homology concept. In contrast, molecular homology is able to offer a definition of homology in genes and proteins that explicates homology by reference to more basic notions. Molecular correspondence originates by means of specific features of causal processes. It is speculated that further understanding of morphogenesis might enable biologists to give a theoretically deeper definition of homology along similar lines: an account which makes reference to the concrete mechanisms that operate in organisms. (shrink)

Serial homology, i.e., homology between repetitive structures in the same individual organism, is a debated concept in evolutionary developmental biology. The central question is the evolutionary interpretation of “sameness” in the context of the same body. This essay provides a synthetic analysis of the main issues involved in the debate, connecting conceptual problems with current experimental research. It is argued that a concept of serial homology that is not of the all-or-nothing kind can smooth several theoretical inconsistencies, (...) while being more in line with what we know about evolutionary change and the way we investigate it. (shrink)

The meaning of the word homology has changed. From being a comparative concept in pre-Darwinian times, it became a historical concept, strictly signifying a common evolutionary origin for either anatomical structures or genes. This historical understanding of homology is not useful in classification; therefore I propose a return to its pre-Darwinian meaning.

Taxa and homologues can in our view be construed both as kinds and as individuals. However, the conceptualization of taxa as natural kinds in the sense of homeostatic property cluster kinds has been criticized by some systematists, as it seems that even such kinds cannot evolve due to their being homeostatic. We reply by arguing that the treatment of transformational and taxic homologies, respectively, as dynamic and static aspects of the same homeostatic property cluster kind represents a good perspective for (...) supporting the conceptualization of taxa as kinds. The focus on a phenomenon of homology based on causal processes (e.g., connectivity, activity-function, genetics, inheritance, and modularity) and implying relationship with modification yields a notion of natural kinds conforming to the phylogenetic-evolutionary framework. Nevertheless, homeostatic property cluster kinds in taxonomic and evolutionary practice must be rooted in the primacy of epistemological classification (homology as observational properties) over metaphysical generalization (series of transformation and common ancestry as unobservational processes). The perspective of individuating characters exclusively by historical-transformational independence instead of their developmental, structural, and functional independence fails to yield a sufficient practical interplay between theory and observation. Purely ontological and ostensional perspectives in evolution and phylogeny (e.g., an ideographic character concept and PhyloCode’s ‘individualism’ of clades) may be pragmatically contested in the case of urgent issues in biodiversity research, conservation, and systematics. (shrink)

Morphological elements, or structures, are sorted into four categories depending on their level of anatomical isolation and the presence or absence of intrinsically identifying characteristics. These four categories are used to highlight the difficulties with the concept of structure and our ability to identify or define structures. The analysis is extended to the concept of homology through a discussion of the methodological and philosophical problems of the current concept of homology. It is argued that homology is fundamentally (...) a similarity based concept rather than a phylogenetic concept, and a proposal is put forth to return to a comparative context for homology. It is shown that for both the concepts of structure and homology ana priori assumption of stable underlying patterns (i.e. archetypes) is essential. (shrink)

The evolutionary embryologist Gavin Rylands de Beer can be viewed as one of the forerunners of modern evolutionary developmental biology in that he posed crucial questions and proposed relevant answers about the causal relationship between ontogeny and phylogeny. In his developmental approach to the phylogenetic phenomenon of homology, he emphasized that homology of morphological structures is to be identified neither with the sameness of the underlying developmental processes nor with the homology of the genes that are in (...) involved in the development of the structures. De Beer’s work on developmental evolution focused on the notion of heterochrony, arguing that paedomorphosis increases morphological evolvability and is thereby an important mode of evolution that accounts for the origin of many taxa, including higher taxa. (shrink)

This work defines homology groups for proof-structures in multiplicative linear logic (see [Gir1], [Gir2], [Dan]). We will show that these groups characterize proof-nets among arbitrary proof-structures, thus obtaining a new correctness criterion and of course a new polynomial algorithm for testing correctness. This homology also bears information on sequentialization. An unexpected geometrical interpretation of the linear connectives is given in the last section. This paper exclusively focuses onabstract proof-structures, i.e. paired-graphs. The relation with actual proofs is investigated in (...) [Gir1], [Gir2], [Dan], [Ret] and [Tro]. (shrink)

Homology is a central concept of comparative and evolutionary biology, referring to the presence of the same bodily parts (e.g., morphological structures) in different species. The existence of homologies is explained by common ancestry, and according to modern definitions of homology, two structures in different species are homologous if they are derived from the same structure in the common ancestor. Homology has traditionally been contrasted with analogy, the presence of similar traits in different species not necessarily due (...) to common ancestry but due to a similar function or convergent evolution resulting from similar selective pressure in different species. (A more recent contrastive notion is homoplasy, the presence of similar traits in different species without common ancestry, i.e., as an instance of parallel evolution.) This sounds straightforward, but in fact the homology concept has a rich history and currently is the subject of extensive theoretical reflection, resulting in different contemporary approaches to homology. (shrink)

Homology continues to be a concept of central importance in the study of phylogenetic relations, but its relation to ontogenetic processes remains problematical. A definition of homology in terms of equivalent morphogenetic processes is defined and applied to the comparative study of tetrapod limbs. This allows for a consistent treatment of relations of similarity and difference of appendage structure in vertebrates, and the distinction between fishes fins and tetrapod limbs in terms of the concept of equivalence is described. (...) The role of genes can also be clarified in this context, in particular the influence of the Hox 4 complex in determining digit character and the homeotic transformations that arise from changes in their expression patterns. It is argued that these observations are not compatible with the notion of homology between individual digits (I, II, III, etc.) across the tetrapods, and that homology cannot be consistently identified with gene action. The relations between homology and the properties of the morphogenetic limb field are discussed. (shrink)

Freud’s late works established the schema of a more or less inexorable civilizational course built around one drive—the death drive—despite his emphatic insistence on a dual structure of two drives. This schema became influential for Critical Theory and in a more subterranean way, also for decolonial thought, and has been widely invoked during the pandemic. It indicates the extent to which drive, destruction, and mastery have consolidated into a, which not only fails to be dislodged by but even informs Derrida’s (...) readings of Freud. Instead, we have to be attentive to the play of homology in Freud as of life, psyche, and civilization, as archaic inheritance. Freudian homology distinguishes itself from what Derrida called “genealogical drive.” The Freudian assumptions in this regard need to be addressed in a step beyond which works with a concept of origin—as its own interruption—that can neither comprehend nor deconstruct the concept of origin as a single and perpetually active homological power as is to be found in Freud. (shrink)

Neural reuse theories suggest that, in the course of evolution, a brain structure may acquire or lose a number of cognitive uses while maintaining its cognitive workings (or low-level operations) fixed. This, in turn, suggests that homologous structures may have very different cognitive uses, while sharing the same workings. And this, essentially, is homology thinking applied to brain function.

The concept of homology arose from classical studies of comprative morphology, and took on a new signficance with the advent of evolutionary theory. It is currentlyl undergoing antoher metamorphosis: many developmental geneticists now dfine homology as shared patterns of gene expression. However, this ne usage conflaes difinition with criteri, and fails to recognize the meaninful asignments of homology must speify a biologcal level. We argue the although developmental genetic data can help identify homologus structures. they are niether (...) necessary nor sufficient, and do not in any case jutify a new definition of homology. (shrink)

Many of the current comparisons of taxic phylogenetic and biological homology in the context of morphology focus on what are seen as categorical distinctions between the two concepts. The first, it is claimed, identifies historical patterns of conservation and variation relating taxa; the second provides a causal framework for the explanation of this conservation and variation. This leads to the conclusion that the two need not be placed in conflict and are in fact compatible, having non-competing epistemic purposes or (...) mapping the same extensions in the form of monophyletic groupings (see Roth, The biological basis of homology 1–26, 1988; Sluys, J Zool Syst Evol Res 34:145–152, 1996; Abouheif, Trends Ecol Evol 12:405–408, 1997; Brigandt, J Exp Zool 299:9–17, 2003, Biol Philos 22:709–725, 2007; Assis and Brigandt, Evol Biol 36:248–255, 2009). This article argues that moves in this direction miss the essential disagreement between these concepts as they have been developed in the context of the debate concerning the best concept for evolutionary investigation. We should rather see these concepts employing a common fundamental methodological approach to homology, but disagreeing about how to apply the methodology effectively. Both concepts employ class reasoning, which pursues homologies as units of generalization—more precisely, as sources of reliable and relevant group-bound information in the form of shared underlying causes. The dispute can be better understood by two poles that structure such reasoning: the need for a reliable basis for projections about the causal history of shared structures, and the desire to identify homologous characters with more informative and specific causal information relevant to generalizing about evolutionary processes. Judgments in favor of one or the other in turn have affected the scope or extension of these competing homology concepts. (shrink)

Homology has been one of, if not the most, fecund concepts which has been used towards the understanding of the genomes of the model organisms. The evidence for this claim can be supported best with an examination of current research in comparative genomics. In comparative genomics, the information of genes or segments of the genome, and their location and sequence, are used to search for genes similar to them, known as 'homologues'. Homologues can be either within that same organism (...) (paralogues), or among different species (orthologues). The importance in finding homologous genes within organisms or across species is that these similarities indicate the possibility of ascribing functions, mechanisms or structures which are required by a variety of species which present the same homology. The interest in structures and functions of genes and proteins common to multiple species is one of the main foci of comparative genomics. Because of this, research into the conservation of genes has been the basis of comparison with regards to homologous genes among diverse organisms. Different causal processes are involved in genetic pathways and mechanisms. Explanations of these depend upon which pathway, structure or mechanism is picked out. Each process has a different causal network to which different explanations refer. What comparative genomics explains are the different causal mechanisms which occur in processes such as differentiation, protein synthesis, and gene regulation. How these processes interact within the organism can only be understood when compared with organisms which possess homologous genes, gene sequences, similar developmental mechanisms, or those whose mechanisms for gene regulation are similar. Explanations which result from comparative genomics contribute to a more comprehensive understanding of both the complex structures and the diverse functions within the genomes of different organisms. There are two related problems which have plagued attempts to define the concept of homology. The first problem arises in clarifying what kind of similarity is involved in a homological comparison. A second problem occurs if more than one concept of homology is needed to pick out the kinds of similarity in different contexts of homological comparison. Homology is usually understood as picking out what counts as 'the same' between two or more organisms. Many of the attempts which have been made to define the concept of homology focus on which criteria are used to restrict the kinds of similarity which exist between two or more organisms or parts being compared. These are criteria which can be used reliably to infer shared ancestry. However, there have been many different attempts to define similarity which have produced a profusion of homology concepts. This profusion has led both to the conflation of what counts as 'the same' in different contexts and has also muddled the relations of comparison which various concepts use to identify homologues. (shrink)

My aim in this paper is twofold. First, I provide an analysis of the notion of cognitive homology. In contrast with the well-known concept of structural homology in biology—defined as the same structure in different animals regardless of form and function—the notion of cognitive homology captures the idea that the basic cognitive contribution of a given homologous brain structure tends to remain stable over long evolutionary time scales. Second, I argue that this notion provides a powerful (...) conceptual tool for the study of cognition. Since a cognitive homology will often consist of an evolutionarily conserved relationship between a homologous brain structure and its basic cognitive contribution, such structure–function mappings can be conceived as basic building blocks of human cognition. (shrink)

Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds to (...) replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability. (shrink)

Serial homology is widespread in organismal design, but the origin and individuation of these repeated structures appears to differ with the different types of serial homologues, and remains an intriguing and exciting topic of research. Here I focus on the evolution of the serially repeated eyespots that decorate the margin of the wings of nymphalid butterflies. In this system, unresolved questions relate to the evolutionary steps that lead to the appearance of these serial homologues and how their separate identities (...) evolved. I present and discuss two alternative hypotheses. The first proposes that eyespots first appeared as a row of undifferentiated repeated modules, one per wing compartment, that later become individuated. This individuation allowed eyespots to appear and disappear from specific wing compartments and also allowed eyespots to acquire different morphologies. The second hypothesis proposes that eyespots first appeared as individuated single units, or groups of units, that over evolutionary time were co‐opted into new compartments on the wing. I discuss the merits of each of these alternate hypotheses by finding analogies to other systems and propose research avenues for addressing these issues in the future. BioEssays 30:358–366, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

MutL family proteins contain an N‐terminal ATPase domain (NTD), an unstructured interdomain linker, and a C‐terminal domain (CTD), which mediates constitutive dimerization between subunits and often contains an endonuclease active site. Most MutL homologs direct strand‐specific DNA mismatch repair by cleaving the error‐containing daughter DNA strand. The strand cleavage reaction is poorly understood; however, the structure of the endonuclease active site is consistent with a two‐ or three‐metal ion cleavage mechanism. A motif required for this endonuclease activity is present in (...) the unstructured linker of Mlh1 and is conserved in all eukaryotic Mlh1 proteins, except those from metamonads, which also lack the almost absolutely conserved Mlh1 C‐terminal phenylalanine‐glutamate‐arginine‐cysteine (FERC) sequence. We hypothesize that the cysteine in the FERC sequence is autoinhibitory, as it sequesters the active site. We further hypothesize that the evolutionary co‐occurrence of the conserved linker motif with the FERC sequence indicates a functional interaction, possibly by linker motif‐mediated displacement of the inhibitory cysteine. This role is consistent with available data for interactions between the linker motif with DNA and the CTDs in the vicinity of the active site. (shrink)

We report evidence further supporting homology between proteins in the F1FO‐ATP synthetase and the bacterial flagellar motor (BFM). BFM proteins FliH, FliI, and FliJ have been hypothesized to be homologous to FO‐b + F1‐δ, F1‐α/β, and F1‐γ, with similar structure and interactions. We conduct a further test by constructing a gene order dataset, examining the order offliH,fliI, andfliJgenes across the phylogenetic breadth of flagellar and nonflagellar type 3 secretion systems, and comparing this to published surveys of gene order in (...) the F1FO‐ATP synthetase, its N‐ATPase relatives, and the bacterial/archaeal V‐ and A‐type ATPases. Strikingly, thefliHIJgene order was deeply conserved, with the few exceptions appearing derived, and exactly matching the widely conserved F‐ATPase gene orderatpFHAG, coding for subunits b‐δ‐α‐γ. The V/A‐type ATPases have a similar conserved gene order. Our results confirm homology between these systems, and suggest a rare case of synteny conserved over billions of years, predating the Last Universal Common Ancestor (LUCA). (shrink)

We discuss N. I. Vavilov’s 1922 landmark publication, “The Law of Homologous Series in Variation,” and highlight its salient points. Vavilov drew upon his considerable experience in the field with wild and cultivated crop plants and summarized what he noticed in the form of a law. The law stated that comparable variant forms tended to appear in different varieties of the same species, different species of the same genus, different genera of the same family, and so on. His survey of (...) the older literature suggested that the law applied to multicellular animals as well. Vavilov acknowledged that such “parallel” series might be the outcome of convergent evolution (as conventionally understood). At the same time, by way of an alternative hypothesis, he posed a question that continues to engage evolutionary biology to this day. Namely, does the existence of such parallelisms reflect underlying structural and developmental principles (based on the laws of physics and chemistry) which constrain the range of possible plant and animal forms? Vavilov’s original 1922 paper from the _Journal of Genetics_ (12:47–89) is available as supplementary material in the online version of this article. (shrink)

The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto‐oncogene int‐1. Homology between these two genes connected oncogenesis to cell‐cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell‐to‐cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell‐nonautonomy of wingless in patterning multiple embryonic and adult (...) structures solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int‐1 was then isolated, and predicted to encode a secreted proto‐oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell‐cell signal had been identified and connected cancer to development. (shrink)

The Drosophila Bolwig organs are small photoreceptor bundles that facilitate the phototactic behavior of the larva. Comparative literature suggests that these highly reduced visual organs share evolutionary ancestry with the adult compound eye. A recent molecular genetic study produced the first detailed account of the mechanisms controlling differential opsin expression and photoreceptor subtype determination in these enigmatic eyes of the Drosophila larva. Here, the evolutionary implications are examined, taking into account the dynamic diversification of opsin genes and the spatial regulation (...) of opsin homolog expression in other insects. It is concluded that, consistent with their common evolutionary roots, the Drosophila larval and adult eyes use the same mechanisms for the regulation of opsin expression and photoreceptor cell fate specification. Strikingly, the structurally highly derived Bolwig organs retained a more ancestral state of opsin expression and regulation. Inconspicuous in size, the Drosophila larval eyes deliver useful lessons in the reconstruction of homology between neuronal cell types with gene expression data, and on the conservative nature of gene regulatory network evolution during the emergence of novel organs from ancestral templates. BioEssays 30:980–993, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Cytoplasmic protein-tyrosine kinases (PTKs) are enzymes involved in transducing a vast number of signals in metazoans. The importance of the Tec family of kinases was immediately recognized when, in 1993, mutations in the gene encoding Bruton's tyrosine kinase (Btk) were reported to cause the human disease X-linked agammaglobulinemia (XLA).(1,2) Since then, additional kinases belonging to this family have been isolated, and the availability of full genome sequences allows identification of all members in selected species enabling phylogenetic considerations. Tec kinases are (...) endowed with Pleckstrin homology (PH) and Tec homology (TH) domains and are involved in diverse biological processes related to the control of survival and differentiation fate. Membrane translocation resulting in the activation of Tec kinases with subsequent Ca2+ release seems to be a general feature. However, nuclear translocation may also be of importance. The purpose of this essay is to characterize members of the Tec family and discuss their involvement in signaling. The three-dimensional structure, expression pattern and evolutionary aspects will also be considered. BioEssays 23:436–446, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

This article discusses the problem of the influence of the Leibniz' continuity principle on the concept of structural plan and homology formation in biology. The concept of body plan was established for the justification of the thesis about the structural sameness of the all living objects at the organismal level. However, the continuity hypothes is testing which was made on the comparative anatomical material has showed the impossibility of reducing the animals structure explanation to the single plan. (...) The idea of organic evolution has made it possible to present the continuity of the organic world as a historical consistency. From an evolutionary point of view homology was interpreted as a homogeny. That made it possible to consider the continuity of the organic world on the suborganismal level. This hypothesis was tested on the embryological material. The results, however, showed that the morphological structures, which seemed to be identical according to the first criterion of the Remane homology and occurred epigenetically, are not really gomogenic. This fact does not allow us to recognize the continuity ofthe organic world on the suborganismal level. The key concepts of classical biological disciplines (comparative anatomy, systematics, evolutionism) could be reconciled only on the basis ofthe discrete principle. (shrink)

The actin crosslinking proteins exhibit marked diversity in size and shape and crosslink actin filaments in different ways. Amino acid sequence analysis of many of these proteins has provided clues to the origin of their diversity. Spectrin, α‐actinin, ABP‐120, ABP‐280, fimbrin, and dystrophin share a homologous sequence segment that is implicated as the common actin binding domain. The remainder of each protein consists of repetitive and non‐repetitive sequence segments that have been shuffled and multiplied in evolution to produce a variety (...) of proteins that are related in function and in composition, but that differ significantly in structure. (shrink)

Replication protein A (RPA) is the main eukaryotic single‐stranded DNA (ssDNA) binding protein, having essential roles in all DNA metabolic reactions involving ssDNA. RPA binds ssDNA with high affinity, thereby preventing the formation of secondary structures and protecting ssDNA from the action of nucleases, and directly interacts with other DNA processing proteins. Here, we discuss recent results supporting the idea that one function of RPA is to prevent annealing between short repeats that can lead to chromosome rearrangements by microhomology‐mediated end (...) joining or the formation of hairpin structures that are substrates for structure‐selective nucleases. We suggest that replication fork catastrophe caused by depletion of RPA could result from cleavage of secondary structures by nucleases, and that failure to cleave hairpin structures formed at DNA ends could lead to gene amplification. These studies highlight the important role RPA plays in maintaining genome integrity. (shrink)

Understanding the organization of an organism by individuating meaningful parts and accounting for organismal properties by studying the interaction of bodily parts is a central practice in many areas of biology. While structures are obvious bodily parts and structure and function have often been seen as antagonistic principles in the study of organismal organization, my tenet is that structures and functions are on a par. I articulate a notion of function (functions as activities), according to which functions are bodily parts (...) just as structures are. Recognizing part-whole relations among an organism’s various structures and functions permits fruitful investigation and multilevel explanation of organismal properties and functioning, across both developmental and evolutionary time. I show how my perspective clarifies debates surrounding homology and evolutionary novelty that stem from an alleged structure-function dichotomy. My approach favors a pluralism about individuation, where the criteria of what counts as a meaningful bodily part depend on the particular epistemic aims pursued in a scientific context. (shrink)

I agree with the view expressed in the target article that the early structural organization of the mammalian neocortex (the primordial neocortical organization) is different from its final one and resembles the more primitive organization of reptilian cortex. During the early development of the neocortex, a distinctly mammalian multilayered pyramidal-cell plate is introduced within a more primitive reptilian-like cortex, establishing simultaneously layer I (marginal zone) above it and layer VII (subplate zone) below it. This multilayered pyramidal-cell plate represents a (...) recent mammalian innovation in the evolution of the cerebral cortex of vertebrates. Hence, the term neocortex is preferable to isocortex. (shrink)

Research in anthropology has shown that kin terminologies have a complex combinatorial structure and vary systematically across cultures. This article argues that universals and variation in kin terminology result from the interaction of (1) an innate conceptual structure of kinship, homologous with conceptual structure in other domains, and (2) principles of optimal, “grammatical” communication active in language in general. Kin terms from two languages, English and Seneca, show how terminologies that look very different on the surface may result from variation (...) in the rankings of a universal set of constraints. Constraints on kin terms form a system: some are concerned with absolute features of kin (sex), others with the position (distance and direction) of kin in “kinship space,” others with groups and group boundaries (matrilines, patrilines, generations, etc.). Also, kin terms sometimes extend indefinitely via recursion, and recursion in kin terminology has parallels with recursion in other areas of language. Thus the study of kinship sheds light on two areas of cognition, and their phylogeny. The conceptual structure of kinship seems to borrow its organization from the conceptual structure of space, while being specialized for representing genealogy. And the grammar of kinship looks like the product of an evolved grammar faculty, opportunistically active across traditional domains of semantics, syntax, and phonology. Grammar is best understood as an offshoot of a uniquely human capacity for playing coordination games. (shrink)

During the course of evolution, variations of a protein sequence is an ongoing phenomenon however limited by the need to maintain its structural and functional integrity. Deciphering the evolutionary path of a protein is thus of fundamental interest. With the development of new methods to visualize high dimension spaces and the improvement of phylogenetic analysis tools, it is possible to study the evolutionary trajectories of proteins in the sequence space. Using the data-driven high-dimensional scaling method, we show that it (...) is possible to predict and represent potential evolutionary trajectories by representing phylogenetic trees into a 3D projection of the sequence space. With the case of the aminodeoxychorismate synthase, an enzyme involved in folate synthesis, we show that this representation raises interesting questions about the complexity of the evolution of a given biological function, in particular concerning its capacity to explore the sequence space. (shrink)

Actin plays several essential roles in cellular processes and is a vital component in the contractile apparatus. To accomplish its many cellular tasks, actin must interact with a wide range of other proteins in addition to self‐assembling into filaments. Characterization of these functional domains and localized binding regions on the actin monomer is therefore an important undertaking. Strategies for elucidating the many interaction sites include X‐ray diffraction, NMR and fluorescence spectroscopy, chemical modification, chemical cross‐linking, protein cleavage, and the study of (...) sequence homologies between the many isotypes of actin. Based on these varied data, we discuss the possible spatial relationships between the interaction sites. (shrink)

Human cholinesterase has recently been sequenced and cloned. It is a glycoprotein of 4 identical subunits, each subunit containing 9 carbohydrate chains and 3.5 disulfide bonds. Protein folding is likely to be very similar in human cholinesterase and Torpedo acetylcholinesterase. The cholinesterases have no significant sequence homology with the serine proteases and seem to belong to a separate serine esterase family.

Numerous accessory factors modulate RNA polymerase response to regulatory signals and cellular cues and establish communications with co‐transcriptional RNA processing. Transcription regulators are astonishingly diverse, with similar mechanisms arising via convergent evolution. NusG/Spt5 elongation factors comprise the only universally conserved and ancient family of regulators. They bind to the conserved clamp helices domain of RNA polymerase, which also interacts with non‐homologous initiation factors in all domains of life, and reach across the DNA channel to form processivity clamps that enable uninterrupted (...) RNA chain synthesis. In addition to this ubiquitous function, NusG homologs exert diverse, and sometimes opposite, effects on gene expression by competing with each other and other regulators for binding to the clamp helices and by recruiting auxiliary factors that facilitate termination, antitermination, splicing, translation, etc. This surprisingly diverse range of activities and the underlying unprecedented structural changes make studies of these “transformer” proteins both challenging and rewarding. (shrink)

We now know the structures of over 200 proteins to atomic resolution. Despite the impressive extent and quality of the results, crystal‐structure analysis has often been thought of as limited in scope, not only in its restriction to samples that can be crystallized, but in the more important respect that taking ‘snapshots’ of proteins does not directly address the complex spatio‐temporal organization of the processes in which proteins participate. It is suggested here that, as the field has matured, this second (...) limitation is gradually being overcome. As we gain increased access to structures of proteins in different conformational states – for example, in conformations produced by different states of ligation – and to families of homologous proteins, we can proceed from the statics of protein structure to the dynamics of conformational change, function, and evolution.A new scientific speciality has grown up around the solved structures: it has as its goal the elucidation of general principles of protein structure and function, to provide a theoretical framework for understanding the properties of proteins revealed by experiment. In this article we shall discuss some of the activity in this field. It will emerge clearly, I believe, that the increasing number and variety of solved structures is exerting a cumulative force. General principles are emerging from comparisons of related proteins and contrasts of dissimilar ones: the whole corpus of data is greater than the sum of the parts. (shrink)

Understanding how conceptual structures inform stone tool production and use would help us resolve the issue of a pongid-hominid dichotomy in brain organisation and cognitive ability. Evidence from ideational apraxia suggests that the planning of linguistic and manipulative behaviours is not colocalized in homologous circuits. An alternative account in terms of the evolutionary expansion of the whole prefrontal-premotor area may be more plausible.

Homologous operational localization processes are effectuated in terms of generalized topological covering systems on structures of physical events. We study localization systems of quantum events' structures by means of Gtothendieck topologies on the base category of Boolean events' algebras. We show that a quantum events algebra is represented by means of a Grothendieck sheaf-theoretic fibred structure, with respect to the global partial order of quantum events' fibres over the base category of local Boolean frames.

Villin, a calcium‐regulated actin‐binding protein, modulates the structure and assembly of actin filaments in vitro. It is organized into three domains, the first two of which are homologous. Villin is mainly produced in epithelial cells that develop a brush border and which are responsible for nutrient uptake. Expression of the villin structural gene is precisely regulated during mouse embryogenesis and is restricted in adults, to certain epithelia of the gastrointestinal and urogenital tracts. The function of villin has been assessed (...) by transfecting CV1 cells with a human cDNA encoding wild‐type villin or mutant villin. Synthesis of large amounts of villin in cells which do not normally produce this protein induces the growth of microvilli on the cell surface and the redistribution of F‐actin, concomitant with the disappearance of stress fibers. The complete villin sequence is required for the morphogenic effect. These results suggest that villin plays a key role in the morphogenesis of microvilli. (shrink)

This dissertation reassesses the complex philosophical relationship between Sartre and psychoanalysis. Most scholarship on this topic focuses on Sartre’s criticisms of the unconscious as anathema both to his conception of the human psyche as devoid of any hidden depths or mental compartments and, correlatively, his account of human freedom. Many philosophers conclude that there is little common ground between Sartrean existentialism and psychoanalytic theory. I argue, on the contrary, that by shifting the emphasis from concerns about the nature of the (...) unconscious to questions about the role of imagination in psychical life, we can see that Sartre and Freudian-Lacanian psychoanalytic theory develop strikingly similar accounts of human subjectivity. After establishing the historical background of Sartre’s career-long engagement with psychoanalysis, I demonstrate the proximity of Sartre and Lacan on the nature of unconscious thought. I proceed to develop the claim that there is a homology between the concept of unconscious fantasy in psychoanalysis and the concept of the imaginary in Sartre’s philosophical corpus. Despite the concept of fantasy being one of the more structuralist-inspired aspects of Lacan’s metapsychology, I show that Sartre’s concept of the imaginary is likewise a structural feature of the psyche, one which establishes the coordinates within which the subject engages with the world. For Sartre, Freud, and Lacan fantasies form the core of subjectivity, giving form to the basic patterns of one’s character. Taken together, these three thinkers furnish a nuanced view of fantasy/the imaginary. On the one hand it is determining insofar as it is responsible for many of the psychopathologies met with in psychoanalysis. On the other hand, it is liberating insofar as the agency of the subject is implicated in the formation of fantasy. I thereby show that Sartre does not fit the caricatured picture of a radical voluntarist that is often attributed to him and that psychoanalysis can accommodate a conception of human freedom. (shrink)

The domain of phenomenological investigation delineated by the Husserlian term authentic empathy presents us with an immediate tension. On the one hand, authentic empathy is supposed to grant the subject access (in some sense that remains to be fully specified) to the Other’s experience. On the other hand, foundational phenomenological considerations pertaining to the apprehension of a foreign subjectivity determine that it is precisely a disjunction in subjective processes that is constitutive of the Other being other. In my approach to (...) this problem, I seek, within the context of a reading of Edith Stein’s work 'On the Problem of Empathy', to clarify the place of ascription in authentic empathy, and to render more explicit a certain notion of “contiguity” that I take to be informing Stein’s understanding of the co-givenness of the Other’s mental life. I go on to argue that a resolution to the problem of empathy lies in the idea that the respective lived experiences of self and Other are, as a matter of descriptive fact, phenomenally connected by a relation of resemblance, and that, consonantly, the essential structure of authentic empathy is characterised in its mature phases by an homological relation to picture consciousness. (shrink)

The domain of phenomenological investigation delineated by the Husserlian term authentic empathy presents us with an immediate tension. On the one hand, authentic empathy is supposed to grant the subject access (in some sense that remains to be fully specified) to the Other’s experience. On the other hand, foundational phenomenological considerations pertaining to the apprehension of a foreign subjectivity determine that it is precisely a disjunction in subjective processes that is constitutive of the Other being other. In my approach to (...) this problem, I seek, within the context of a reading of Edith Stein’s work On the Problem of Empathy, to clarify the place of ascription in authentic empathy, and to render more explicit a certain notion of “contiguity” that I take to be informing Stein’s understanding of the co-givenness of the Other’s mental life. I go on to argue that a resolution to the problem of empathy lies in the idea that the respective lived experiences of self and Other are, as a matter of descriptive fact, phenomenally connected by a relation of resemblance, and that, consonantly, the essential structure of authentic empathy is characterised in its mature phases by an homological relation to picture consciousness. (shrink)

hiCLIP (RNA hybrid and individual‐nucleotide resolution ultraviolet cross‐linking and immunoprecipitation), is a novel technique developed by Sugimoto et al. (2015). Here, the use of different adaptors permits a controlled ligation of the two strands of a RNA duplex allowing the identification of each arm in the duplex upon sequencing. The authors chose a notoriously difficult to study double‐stranded RNA‐binding protein (dsRBP) termed Staufen1, a mammalian homolog of Drosophila Staufen involved in mRNA localization and translational control. Using hiCLIP, they discovered a (...) dominance of intramolecular RNA duplexes compared to the total RNA duplexes identified. Importantly, the authors discovered two different types of intramolecular duplexes in the cell: highly translated mRNAs with long‐range duplexes in their 3′‐UTRs and poorly translated mRNAs with duplexes in their coding region. In conclusion, the authors establish hiCLIP as an important novel technique for the identification of RNA secondary structures that serve as in vivo binding sites for dsRBPs. (shrink)

Unlike the most well‐characterized prokaryotic polymerase, E. Coli DNA pol I, none of the eukaryotic polymerases have their own 5′ to 3′ exonuclease domain for nick translation and Okazaki fragment processing. In eukaryotes, FEN‐1 is an endo‐and exonuclease that carries out this function independently of the polymerase molecules. Only seven nucleases have been cloned from multicellular eukaryotic cells. Among these, FEN‐1 is intriguing because it has complex structural preferences; specifically, it cleaves at branched DNA structures. The cloning of FEN‐1 (...) permitted establishment of the first eukaryotic nuclease family, predicting that S. cerevisiae RAD2 (S. pombe Rad13) and its mammalian homolog, XPG, would have similar structural specficity. The FEN‐1 nuclease family includes several similar enzymes encoded by bacteriophages. The crystal structures of two enzymes in the FEN‐1 nuclease family have been solved and they provide a structural basis for the interesting steric requirements of FEN‐1 substrates. Because of their unique structural specificities, FEN‐1 and its family members have important roles in DNA replication, repair and, potentially, recombination. Recently, FEN‐1 was found to specifically associate with PCNA, explaining some aspects of FEN‐1 function during DNA replication and potentially in DNA repair. (shrink)

The nuclear envelope has recently become the object of intense scrutiny because it is the site of nuclear transport and is possibly involved in the organization of the interphase genome, thereby affecting gene expression. The major structural support for the nuclear envelope is the nuclear lamina, composed of the nuclear lamin proteins. They lie on the surface of the inner nuclear membrane and are in direct contact with the chromatin at the edge of the nucleus. The structure of the (...) nuclear lamin proteins has recently been deduced from their cDNAs and shown to have remarkable homologies to the family of cytoplasmic intermediate filaments. However, the lamin proteins have been found to depolymerize in response to metaphase‐specific phosphorylation events, and reassemble around daughter chromosomes at the completion of cell division. Little is known of the mechanisms of these dynamics, nor of other post‐translational modifications evident in these proteins. In addition, we have as yet no concrete idea of the function of these highly conserved proteins in the cell. This review will summarize our present knowledge of nuclear lamin structure and the new experimental approaches designed to elucidate their function. (shrink)

A large proportion of tumour‐associated antigens seem to be determined by carbohydrate structures. Advances in the study of the antigenicity of cell‐surface carbohydrates have been hampered by the absence of advanced monoclonal hybridoma technology comparable to that available for the study of protein antigens. Monoclonal antibodies have been raised against a carbohydrate epitope (43–9F) that is associated with the proliferative features of squamous lung carcinomas. These were used in turn to generate anti‐idiotype antibodies with homology to 43–9F. The method (...) and its possible applications are described, together with a procedure to detect rare cell membrane variants within large populations. (shrink)