A field study of 29 resource-constrained firms that varied dramatically in their responses to similar objective environments is used to examine the process by which entrepreneurs in resource-poor environments were able to render unique services by recombining elements at hand for new purposes that challenged institutional definitions and limits. We found that Levi-Strauss's concept of bricolage—making do with what is at hand—explained many of the behaviors we observed in small firms that were able to create something from nothing by exploiting physical, social, or institutional inputs that other firms rejected or ignored. We demonstrate the socially constructed nature of resource environments and the role of bricolage in this construction. Using our field data and the existing literature on bricolage, we advance a formal definition of entrepreneurial bricolage and induce the beginnings of a process model of bricolage and firm growth. Central to our contribution is the notion that companies engaging in bri...

Creating Something from Nothing: Resource Construction through Entrepreneurial Bricolage:

Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.

/pdf/the-evolution-of-transcriptional-regulation-in-eukaryotes-16fy43qset.pdf

The Evolution of Transcriptional Regulation in Eukaryotes

Transcriptional control is a major mechanism for regulating gene expression. The complex machinery required to effect this control is still emerging from functional and evolutionary analysis of genomic architecture. In addition to the promoter, many other regulatory elements are required for spatiotemporally and quantitatively correct gene expression. Enhancer and repressor elements may reside in introns or up- and downstream of the transcription unit. For some genes with highly complex expression patterns—often those that function as key developmental control genes—the cis-regulatory domain can extend long distances outside the transcription unit. Some of the earliest hints of this came from disease-associated chromosomal breaks positioned well outside the relevant gene. With the availability of wide-ranging genome sequence comparisons, strong conservation of many noncoding regions became obvious. Functional studies have shown many of these conserved sites to be transcriptional regulatory elements that sometimes reside inside unrelated neighboring genes. Such sequence-conserved elements generally harbor sites for tissue-specific DNA-binding proteins. Developmentally variable chromatin conformation can control protein access to these sites and can regulate transcription. Disruption of these finely tuned mechanisms can cause disease. Some regulatory element mutations will be associated with phenotypes distinct from any identified for coding-region mutations.

/pdf/long-range-control-of-gene-expression-emerging-mechanisms-p5umy3l9de.pdf

Long-range control of gene expression: emerging mechanisms and disruption in disease.

Scientific activities take place within the structured sets of ideas and assumptions that define a field and its practices. The conceptual framework of evolutionary biology emerged with the Modern Synthesis in the early twentieth century and has since expanded into a highly successful research program to explore the processes of diversification and adaptation. Nonetheless, the ability of that framework satisfactorily to accommodate the rapid advances in developmental biology, genomics and ecology has been questioned. We review some of these arguments, focusing on literatures (evo-devo, developmental plasticity, inclusive inheritance and niche construction) whose implications for evolution can be interpreted in two ways—one that preserves the internal structure of contemporary evolutionary theory and one that points towards an alternative conceptual framework. The latter, which we label the 'extended evolutionary synthesis' (EES), retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution, and reciprocal portrayals of causation. In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism-environment complementarity. We spell out the structure, core assumptions and novel predictions of the EES, and show how it can be deployed to stimulate and advance research in those fields that study or use evolutionary biology.

https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2015.1019

The extended evolutionary synthesis: its structure, assumptions and predictions.

Around 98% of all transcriptional output in humans is noncoding RNA. RNA-mediated gene regulation is widespread in higher eukaryotes and complex genetic phenomena like RNA interference, co-suppression, transgene silencing, imprinting, methylation, and possibly position-effect variegation and transvection, all involve intersecting pathways based on or connected to RNA signaling. I suggest that the central dogma is incomplete, and that intronic and other non-coding RNAs have evolved to comprise a second tier of gene expression in eukaryotes, which enables the integration and networking of complex suites of gene activity. Although proteins are the fundamental effectors of cellular function, the basis of eukaryotic complexity and phenotypic variation may lie primarily in a control architecture composed of a highly parallel system of trans-acting RNAs that relay state information required for the coordination and modulation of gene expression, via chromatin remodeling, RNA–DNA, RNA–RNA and RNA–protein interactions. This system has interesting and perhaps informative analogies with small world networks and dataflow computing.

/pdf/non-coding-rnas-the-architects-of-eukaryotic-complexity-4tvjjsfxla.pdf

Non-coding RNAs: the architects of eukaryotic complexity

Charles Darwin, while trying to devise a general theory of heredity from the observations of animal and plant breeders, discovered that domesticated mammals possess a distinctive and unusual suite of heritable traits not seen in their wild progenitors. Some of these traits also appear in domesticated birds and fish. The origin of Darwin's "domestication syndrome" has remained a conundrum for more than 140 years. Most explanations focus on particular traits, while neglecting others, or on the possible selective factors involved in domestication rather than the underlying developmental and genetic causes of these traits. Here, we propose that the domestication syndrome results predominantly from mild neural crest cell deficits during embryonic development. Most of the modified traits, both morphological and physiological, can be readily explained as direct consequences of such deficiencies, while other traits are explicable as indirect consequences. We first show how the hypothesis can account for the multiple, apparently unrelated traits of the syndrome and then explore its genetic dimensions and predictions, reviewing the available genetic evidence. The article concludes with a brief discussion of some genetic and developmental questions raised by the idea, along with specific predictions and experimental tests.

/pdf/the-domestication-syndrome-in-mammals-a-unified-explanation-z2gitp87su.pdf

The “Domestication Syndrome” in Mammals: A Unified Explanation Based on Neural Crest Cell Behavior and Genetics

The evolution of "bricolage"

Evolution: A View from the 21st Century, written by an eminent microbiologist–bacterial molecular geneticist, is an ambitious book. It has something novel and highly interesting to say about evolution and it deserves to be widely read. Nevertheless, I have found doing this review a difficult exercise. In the interest of ‘‘full disclosure,’’ I should say that the author, Jim Shapiro, is a friend with whom I have previously discussed these ideas. (I had not, however, known about the book until it was published.) Friends, however, do not always agree and he and I have differed about some of his ideas. Nor have those disagreements been dispelled by my reading the book. In particular, I think that there is an alternative interpretation of some of the phenomena presented and cited here as providing support for the central thesis. In addition, I regard one core proposition, though only explicitly stated at the end and then partially hedged, as, simply, wrong. Hence, although I strongly recommend the book and hope that it is widely read and discussed, I cannot equivalently endorse its big idea or, at least, not all of it. In this review, I will first describe the contents of the book and its central thesis and will then try to explain where the problems, in my opinion, reside. A few words first, however, about the author and his pathway into evolution from bacterial molecular genetics, might be appropriate. Jim Shapiro was, as a postdoc in Jonathan Beckwith’s lab in 1969, the first person to purify a small set of protein-coding genes, those of the lac operon (which had been imbedded in a much larger set of phage genes within transducing phages). The strategy was brilliant but was not applicable to most genes, hence, it was superseded by the more general cloning techniques for specific genes that came to the fore in the early 1970s. Nevertheless, it was a milestone in the development of the modern (post60s) form of molecular biology, involving DNA sequence isolation and characterization. Even more significantly, Jim had, as a postdoc with Francois Jacob, the preceding year, discovered that certain mutations in Escherichia coli were due to insertions of bacterial transposable elements, the so-called insertion sequence (IS) elements. The discovery immediately made geneticists aware that the transposable element phenomenon, discovered by Barbara McClintock in maize two decades earlier but dismissed as an oddity by most geneticists, was, almost certainly, a general one, with major implications for mechanisms of gene control, biological development, and evolution (Bukhari et al. 1977). That work eventually led on to a 12-year friendship between Jim and Barbara McClintock, which lasted until her death. In that friendship and exchange of ideas lay the seeds of Jim’s interest in evolution—the major focus of McClintock’s attention in the last decades of her life—and, ultimately, in the thesis developed in this book. The key goal of this book is to demonstrate that a central premise of Darwinian evolution is incorrect and to spell out the implications of that conclusion for evolutionary theory. The Darwinian premise is that genetic variations—‘‘mutations’’ including chromosomal breaks and rearrangements) in current terminology but ‘‘hereditary variations’’ in Darwin’s—occur ‘‘randomly,’’ that is, irrespectively of environmental conditions and adaptive ‘‘need.’’ (Darwin actually equivocated somewhat on this point, at times endorsing the inheritance of acquired characteristics, but he seemed aware that the strong form of his theory required that variations arise by chance, i.e., without respect to future utility, hence randomly.) This central plank of classic Darwinian evolution is also embedded, according to Jim and several others, in a more recent formulation, namely Francis Crick’s ‘‘central dogma,’’ first stated in 1958, and reiterated and (basically reaffirmed) by Crick in 1970. This is the idea that ‘‘information’’ flows one-way from nucleic acids (DNA and RNA) to proteins and never in the reverse direction. From this, Jim argues that it is tantamount to the statement that environmental influences never influence DNA structure and information content; the flow of ‘‘instruction’’ is always one-way, outwards from DNA to proteins and thence to biological properties. (His formulation of this view is that it treats the genome as a ‘‘read only memory’’ storage system.) Whether that extrapolation from Crick’s statement is truly fair is something best left to historians of science. In neither statement, to my eye, was Crick explicitly considering the kinds of organismal response that can alter genomic

Evolution: A View from the 21st Century

The molecular complexity of the Drosophila somatic sex-determination pathway poses formidable intellectual challenges for attempts to explain its evolutionary origins. Here we present a reconstruction of how this regulatory cascade might have evolved in a step-by-step fashion. We illustrate how mutations in genes, which were already part of the pathway or were recruited as new regulators of the pathway, were favored by sexual selection acting on the discriminatory sex-determining signal. This allows us to explain the major features of the pathway, including multiple promoter sites, alternative splicing patterns, autoregulation, and stop codons. Our hypothesis is built on the available data from Drosophila and other insect species, and we point out where it is amenable to further experimental and comparative tests.

/pdf/the-evolution-of-the-drosophila-sex-determination-pathway-5et9ez77di.pdf

The evolution of the Drosophila sex-determination pathway

This paper presents a history of the changing meanings of the term “gene,” over more than a century, and a discussion of why this word, so crucial to genetics, needs redefinition today. In this account, the first two phases of 20th century genetics are designated the “classical” and the “neoclassical” periods, and the current molecular-genetic era the “modern period.” While the first two stages generated increasing clarity about the nature of the gene, the present period features complexity and confusion. Initially, the term “gene” was coined to denote an abstract “unit of inheritance,” to which no specific material attributes were assigned. As the classical and neoclassical periods unfolded, the term became more concrete, first as a dimensionless point on a chromosome, then as a linear segment within a chromosome, and finally as a linear segment in the DNA molecule that encodes a polypeptide chain. This last definition, from the early 1960s, remains the one employed today, but developments since the 1970s have undermined its generality. Indeed, they raise questions about both the utility of the concept of a basic “unit of inheritance” and the long implicit belief that genes are autonomous agents. Here, we review findings that have made the classic molecular definition obsolete and propose a new one based on contemporary knowledge.

https://www.genetics.org/content/genetics/205/4/1353.full.pdf

Adam S. Wilkins

Papers

The “Domestication Syndrome” in Mammals: A Unified Explanation Based on Neural Crest Cell Behavior and Genetics

The evolution of "bricolage"

Evolution: A View from the 21st Century

The evolution of the Drosophila sex-determination pathway

The Evolving Definition of the Term "Gene".