In the 150 years since Darwin, the field of evolutionary biology has left a glaring gap in understanding how animals developed their astounding variety and complexity. The standard answer has been ...that small genetic mutations accumulate over time to produce wondrous innovations such as eyes and wings. Drawing on cutting-edge research across the spectrum of modern biology, Marc Kirschner and John Gerhart demonstrate how this stock answer is woefully inadequate. Rather they offer an original solution to the longstanding puzzle of how small random genetic change can be converted into complex, useful innovations.In a new theory they call "facilitated variation," Kirschner and Gerhart elevate the individual organism from a passive target of natural selection to a central player in the 3-billion-year history of evolution. In clear, accessible language, the authors invite every reader to contemplate daring new ideas about evolution. By closing the major gap in Darwin's theory Kirschner and Gerhart also provide a timely scientific rebuttal to modern critics of evolution who champion "intelligent design."
A biochemical explanation of development from the fertilized egg to the adult requires an understanding of the proteins and RNAs expressed over time during embryogenesis. We present a comprehensive ...characterization of protein and mRNA dynamics across early development in Xenopus. Surprisingly, we find that most protein levels change little and duplicated genes are expressed similarly. While the correlation between protein and mRNA levels is poor, a mass action kinetics model parameterized using protein synthesis and degradation rates regresses protein dynamics to RNA dynamics, corrected for initial protein concentration. This study provides detailed data for absolute levels of ∼10,000 proteins and ∼28,000 transcripts via a convenient web portal, a rich resource for developmental biologists. It underscores the lasting impact of maternal dowry, finds surprisingly few cases where degradation alone drives a change in protein level, and highlights the importance of transcription in shaping the dynamics of the embryonic proteome.
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•A genome-scale resource of mRNA and protein expression for vertebrate embryogenesis•Temporal patterns of change in mRNA and protein abundance are poorly correlated•A simple kinetic model explains protein expression as a function of mRNA levels•Embryogenesis is driven by maternal protein dowry and tissue-specific transcription
Embryos express proteins at the correct time during development, by balancing the maternal contribution with protein synthesis and degradation. Peshkin et al. determine the absolute concentrations of ∼10,000 proteins and ∼28,000 transcripts across Xenopus development, uncovering the relative roles of these three processes across the proteome and revealing global trends.
theory of facilitated variation Gerhart, John; Kirschner, Marc
Proceedings of the National Academy of Sciences - PNAS,
05/2007, Letnik:
104, Številka:
Suppl 1
Journal Article
Recenzirano
Odprti dostop
This theory concerns the means by which animals generate phenotypic variation from genetic change. Most anatomical and physiological traits that have evolved since the Cambrian are, we propose, the ...result of regulatory changes in the usage of various members of a large set of conserved core components that function in development and physiology. Genetic change of the DNA sequences for regulatory elements of DNA, RNAs, and proteins leads to heritable regulatory change, which specifies new combinations of core components, operating in new amounts and states at new times and places in the animal. These new configurations of components comprise new traits. The number and kinds of regulatory changes needed for viable phenotypic variation are determined by the properties of the developmental and physiological processes in which core components serve, in particular by the processes' modularity, robustness, adaptability, capacity to engage in weak regulatory linkage, and exploratory behavior. These properties reduce the number of regulatory changes needed to generate viable selectable phenotypic variation, increase the variety of regulatory targets, reduce the lethality of genetic change, and increase the amount of genetic variation retained by a population. By such reductions and increases, the conserved core processes facilitate the generation of phenotypic variation, which selection thereafter converts to evolutionary and genetic change in the population. Thus, we call it a theory of facilitated phenotypic variation.
The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from ...vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates. We further test the hypothesis by investigating the role of cWnt signaling during early patterning along the A/P axis of the hemichordate Saccoglossus kowalevskii. We have cloned and investigated the expression of the complete Wnt ligand and Frizzled receptor complement of S. kowalevskii during early development along with many secreted Wnt modifiers. Eleven of the 13 Wnt ligands are ectodermally expressed in overlapping domains, predominantly in the posterior, and Wnt antagonists are localized predominantly to the anterior ectoderm in a pattern reminiscent of their distribution in vertebrate embryos. Overexpression and knockdown experiments, in combination with embryological manipulations, establish the importance of cWnt signaling for repression of anterior fates and activation of mid-axial ectodermal fates during the early development of S. kowalevskii. However, surprisingly, terminal posterior fates, defined by posterior Hox genes, are unresponsive to manipulation of cWnt levels during the early establishment of the A/P axis at late blastula and early gastrula. We establish experimental support for a conserved role of Wnt signaling in the early specification of the A/P axis during deuterostome body plan diversification, and further build support for an ancestral role of this pathway in early evolution of the bilaterian A/P axis. We find strong support for a role of cWnt in suppression of anterior fates and promotion of mid-axial fates, but we find no evidence that cWnt signaling plays a role in the early specification of the most posterior axial fates in S. kowalevskii. This posterior autonomy may be a conserved feature of early deuterostome axis specification.
The deuterostome context of chordate origins Lowe, Christopher J; Clarke, D Nathaniel; Medeiros, Daniel M ...
Nature (London),
04/2015, Letnik:
520, Številka:
7548
Journal Article
Recenzirano
Our understanding of vertebrate origins is powerfully informed by comparative morphology, embryology and genomics of chordates, hemichordates and echinoderms, which together make up the deuterostome ...clade. Striking body-plan differences among these phyla have historically hindered the identification of ancestral morphological features, but recent progress in molecular genetics and embryology has revealed deep similarities in body-axis formation and organization across deuterostomes, at stages before morphological differences develop. These developmental genetic features, along with robust support of pharyngeal gill slits as a shared deuterostome character, provide the foundation for the emergence of chordates.
Evolvability Kirschner, Marc; Gerhart, John
Proceedings of the National Academy of Sciences - PNAS,
07/1998, Letnik:
95, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Evolvability is an organism's capacity to generate heritable phenotypic variation. Metazoan evolution is marked by great morphological and physiological diversification, although the core genetic, ...cell biological, and developmental processes are largely conserved. Metazoan diversification has entailed the evolution of various regulatory processes controlling the time, place, and conditions of use of the conserved core processes. These regulatory processes, and certain of the core processes, have special properties relevant to evolutionary change. The properties of versatile protein elements, weak linkage, compartmentation, redundancy, and exploratory behavior reduce the interdependence of components and confer robustness and flexibility on processes during embryonic development and in adult physiology. They also confer evolvability on the organism by reducing constraints on change and allowing the accumulation of nonlethal variation. Evolvability may have been generally selected in the course of selection for robust, flexible processes suitable for complex development and physiology and specifically selected in lineages undergoing repeated radiations.
Hemichordates are an important group for investigating the evolution of bilaterian nervous systems. As the closest chordate outgroup with a bilaterally symmetric adult body plan, hemichordates are ...particularly informative for exploring the origins of chordates. Despite the importance of hemichordate neuroanatomy for testing hypotheses on deuterostome and chordate evolution, adult hemichordate nervous systems have not been comprehensively described using molecular techniques, and classic histological descriptions disagree on basic aspects of nervous system organization. A molecular description of hemichordate nervous system organization is important for both anatomical comparisons across phyla and for attempts to understand how conserved gene regulatory programs for ectodermal patterning relate to morphological evolution in deep time. Here, we describe the basic organization of the adult hemichordate
Saccoglossus kowalevskii
nervous system using immunofluorescence, in situ hybridization, and transgenic reporters to visualize neurons, neuropil, and key neuronal cell types. Consistent with previous descriptions, we found the
S
.
kowalevskii
nervous system consists of a pervasive nerve plexus concentrated in the anterior, along with nerve cords on both the dorsal and ventral side. Neuronal cell types exhibited clear anteroposterior and dorsoventral regionalization in multiple areas of the body. We observed spatially demarcated expression patterns for many genes involved in synthesis or transport of neurotransmitters and neuropeptides but did not observe clear distinctions between putatively centralized and decentralized portions of the nervous system. The plexus shows regionalized structure and is consistent with the proboscis base as a major site for information processing rather than the dorsal nerve cord. In the trunk, there is a clear division of cell types between the dorsal and ventral cords, suggesting differences in function. The absence of neural processes crossing the basement membrane into muscle and extensive axonal varicosities suggest that volume transmission may play an important role in neural function. These data now facilitate more informed neural comparisons between hemichordates and other groups, contributing to broader debates on the origins and evolution of bilaterian nervous systems.
The organizer is formed in an equatorial sector of the blastula stage
amphibian embryo by cells that have responded to two maternal agents: a general
meso-endoderm inducer (involving the TFG-β ...signaling pathway) and a dorsal
modifier (probably involving the Wnt signaling pathway). The meso-endoderm
inducer is secreted by most vegetal cells, those containing maternal materials
that had been localized in the vegetal hemisphere of the oocyte during
oogenesis. As a consequence of the inducer's distribution and action, the
competence domains of prospective ectoderm, mesoderm, and endoderm are
established in an animal-to-vegetal order in the blastula. The dorsal modifier
signal is secreted by a sector of cells of the animal and vegetal hemispheres
on one side of the blastula. These cells contain maternal materials transported
there in the first cell cycle from the vegetal pole of the egg along
microtubules aligned by cortical rotation. The Nieuwkoop center is the region
of blastula cells secreting both maternal signals, and hence specifying the
organizer in an equatorial sector. Final steps of organizer formation at the
late blastula or early gastrula stage may involve locally secreted zygotic
signals as well. At the gastrula stage, the organizer secretes a variety of
zygotic proteins that act as antagonists to various members of the BMP and Wnt
families of ligands, which are secreted by cells of the competence domains
surrounding the organizer. BMPs and Wnts favor ventral development, and cells
near the organizer are protected from these agents by the organizer's
inducers. The nearby cells are derepressed in their inherent capacity for
dorsal development, which is apparent in the neural induction of the ectoderm,
dorsalization of the mesoderm, and anteriorization of the endoderm. The
organizer also engages in extensive specialized morphogenesis, which brings it
within range of responsive cell groups. It also self-differentiates to a
variety of axial tissues of the body.
We have compared the dorsoventral development of hemichordates and chordates to deduce the organization of their common ancestor, and hence to identify the evolutionary modifications of the chordate ...body axis after the lineages split. In the hemichordate embryo, genes encoding bone morphogenetic proteins (Bmp) 2/4 and 5/8, as well as several genes for modulators of Bmp activity, are expressed in a thin stripe of ectoderm on one midline, historically called "dorsal." On the opposite midline, the genes encoding Chordin and Anti-dorsalizing morphogenetic protein (Admp) are expressed. Thus, we find a Bmp-Chordin developmental axis preceding and underlying the anatomical dorsoventral axis of hemichordates, adding to the evidence from Drosophila and chordates that this axis may be at least as ancient as the first bilateral animals. Numerous genes encoding transcription factors and signaling ligands are expressed in the three germ layers of hemichordate embryos in distinct dorsoventral domains, such as pox neuro, pituitary homeobox, distalless, and tbx2/3 on the Bmp side and netrin, mnx, mox, and single-minded on the Chordin-Admp side. When we expose the embryo to excess Bmp protein, or when we deplete endogenous Bmp by small interfering RNA injections, these expression domains expand or contract, reflecting their activation or repression by Bmp, and the embryos develop as dorsalized or ventralized limit forms. Dorsoventral patterning is independent of anterior/posterior patterning, as in Drosophila but not chordates. Unlike both chordates and Drosophila, neural gene expression in hemichordates is not repressed by high Bmp levels, consistent with their development of a diffuse rather than centralized nervous system. We suggest that the common ancestor of hemichordates and chordates did not use its Bmp-Chordin axis to segregate epidermal and neural ectoderm but to pattern many other dorsoventral aspects of the germ layers, including neural cell fates within a diffuse nervous system. Accordingly, centralization was added in the chordate line by neural-epidermal segregation, mediated by the pre-existing Bmp-Chordin axis. Finally, since hemichordates develop the mouth on the non-Bmp side, like arthropods but opposite to chordates, the mouth and Bmp-Chordin axis may have rearranged in the chordate line, one relative to the other.
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