BMP Signaling Components in Embryonic Transcriptomes of the Hover Fly Episyrphus balteatus (Syrphidae)

BMP Signaling Components in Embryonic Transcriptomes of the Hover Fly Episyrphus balteatus (Syrphidae): "Background:
In animals, signaling of Bone Morphogenetic Proteins (BMPs) is essential for dorsoventral (DV) patterning of the embryo, but how BMP signaling evolved with changes in embryonic DV differentiation is largely unclear. Based on the extensive knowledge of BMP signaling in Drosophila melanogaster, the morphological diversity of extraembryonic tissues in different fly species provides a comparative system to address this question. The closest relatives of D. melanogaster with clearly distinct DV differentiation are hover flies (Diptera: Syrphidae). The syrphid Episyrphus balteatus is a commercial bio-agent against aphids and has been established as a model organism for developmental studies and chemical ecology. The dorsal blastoderm of E. balteatus gives rise to two extraembryonic tissues (serosa and amnion), whereas in D. melanogaster, the dorsal blastoderm differentiates into a single extraembryonic epithelium (amnioserosa). Recent studies indicate that several BMP signaling components of D. melanogaster, including the BMP ligand Screw (Scw) and other extracellular regulators, evolved in the dipteran lineage through gene duplication and functional divergence. These findings raise the question of whether the complement of BMP signaling components changed with the origin of the amnioserosa.
Results:
To search for BMP signaling components in E. balteatus, we generated and analyzed transcriptomes of freshly laid eggs (0-30 minutes) and late blastoderm to early germband extension stages (3-6 hours) using Roche/454 sequencing. We identified putative E. balteatus orthologues of 43% of all annotated D. melanogaster genes, including the genes of all BMP ligands and other BMP signaling components.
Conclusion:
The diversification of several BMP signaling components in the dipteran linage of D. melanogaster preceded the origin of the amnioserosa.[Transcriptome sequence data from this study have been deposited at the NCBI Sequence Read Archive (SRP005289); individually assembled sequences have been deposited at GenBank (JN006969-JN006986).]"

Counting individual DNA molecules by the stochastic attachment of diverse labels [Applied Biological Sciences]

Counting individual DNA molecules by the stochastic attachment of diverse labels [Applied Biological Sciences]: "We implement a unique strategy for single molecule counting termed stochastic labeling, where random attachment of a diverse set of labels converts a population of identical DNA molecules into a population of distinct DNA molecules suitable for threshold detection. The conceptual framework for stochastic labeling is developed and experimentally demonstrated by determining the absolute and relative number of selected genes after stochastically labeling approximately 360,000 different fragments of the human genome. The approach does not require the physical separation of molecules and takes advantage of highly parallel methods such as microarray and sequencing technologies to simultaneously count absolute numbers of multiple targets. Stochastic labeling should be particularly useful for determining the absolute numbers of RNA or DNA molecules in single cells."

Evidence of association between Nucleosome Occupancy and the Evolution of Transcription Factor Binding Sites in Yeast

Evidence of association between Nucleosome Occupancy and the Evolution of Transcription Factor Binding Sites in Yeast: "Background:
Divergence of transcription factor binding sites is considered to be an important source of regulatory evolution. The associations between transcription factor binding sites and phenotypic diversity have been investigated in many model organisms. However, the understanding of other factors that contribute to it is still limited. Recent studies have elucidated the effect of chromatin structure on molecular evolution of genomic DNA. Though the profound impact of nucleosome positions on gene regulation has been reported, their influence on transcriptional evolution is still less explored. With the availability of genome-wide nucleosome map in yeast species, it is thus desirable to investigate their impact on transcription factor binding site evolution. Here, we present a comprehensive analysis of the role of nucleosome positioning in the evolution of transcription factor binding sites.
Results:
We compared the transcription factor binding site frequency in nucleosome occupied regions and nucleosome depleted regions in promoters of old (orthologs among Saccharomycetaceae) and young (Saccharomyces specific) genes; and in duplicate gene pairs. We demonstrated that nucleosome occupied regions accommodate greater binding site variations than nucleosome depleted regions in young genes and in duplicate genes. This finding was confirmed by measuring the difference in evolutionary rates of binding sites in sensu stricto yeasts at nucleosome occupied regions and nucleosome depleted regions. The binding sites at nucleosome occupied regions exhibited a consistently higher evolution rate than those at nucleosome depleted regions, corroborating the difference in the selection constraints at the two regions. Finally, through site-directed mutagenesis experiment, we found that binding site gain or loss events at nucleosome depleted regions may cause more expression differences than those in nucleosome occupied regions.
Conclusions:
Our study indicates the existence of different selection constraint on binding sites at nucleosome occupied regions than at the nucleosome depleted regions. We found that the binding sites have a different rate of evolution at nucleosome occupied and depleted regions. Finally, using transcription factor binding site-directed mutagenesis experiment, we confirmed the difference in the impact of binding site changes on expression at these regions. Thus, our work demonstrates the importance of composite analysis of chromatin and transcriptional evolution."

BrainAligner: 3D registration atlases of Drosophila brains

BrainAligner: 3D registration atlases of Drosophila brains: "

BrainAligner: 3D registration atlases of Drosophila brains

Nature Methods 8, 493 (2011).
doi:10.1038/nmeth.1602

Authors: Hanchuan Peng, Phuong Chung, Fuhui Long, Lei Qu, Arnim Jenett, Andrew M Seeds, Eugene W Myers & Julie H Simpson

"

Fast, three-dimensional super-resolution imaging of live cells

Fast, three-dimensional super-resolution imaging of live cells: "

Fast, three-dimensional super-resolution imaging of live cells

Nature Methods 8, 499 (2011).
doi:10.1038/nmeth.1605

Authors: Sara A Jones, Sang-Hee Shim, Jiang He & Xiaowei Zhuang

"

Structure of p300 bound to MEF2 on DNA reveals a mechanism of enhanceosome assembly

Structure of p300 bound to MEF2 on DNA reveals a mechanism of enhanceosome assembly: "

Transcription co-activators CBP and p300 are recruited by sequence-specific transcription factors to specific genomic loci to control gene expression. A highly conserved domain in CBP/p300, the TAZ2 domain, mediates direct interaction with a variety of transcription factors including the myocyte enhancer factor 2 (MEF2). Here we report the crystal structure of a ternary complex of the p300 TAZ2 domain bound to MEF2 on DNA at 2.2Å resolution. The structure reveals three MEF2:DNA complexes binding to different sites of the TAZ2 domain. Using structure-guided mutations and a mammalian two-hybrid assay, we show that all three interfaces contribute to the binding of MEF2 to p300, suggesting that p300 may use one of the three interfaces to interact with MEF2 in different cellular contexts and that one p300 can bind three MEF2:DNA complexes simultaneously. These studies, together with previously characterized TAZ2 complexes bound to different transcription factors, demonstrate the potency and versatility of TAZ2 in protein–protein interactions. Our results also support a model wherein p300 promotes the assembly of a higher-order enhanceosome by simultaneous interactions with multiple DNA-bound transcription factors.

"

[Report] Diffusible Signals, Not Autonomous Mechanisms, Determine the Main Proximodistal Limb Subdivision

[Report] Diffusible Signals, Not Autonomous Mechanisms, Determine the Main Proximodistal Limb Subdivision: "Cells compare proximal and distal signals to set their identity along the vertebrate limb.

Authors: Alberto Roselló-Díez, María A. Ros, Miguel Torres"

[Report] Initiation of Proximal-Distal Patterning in the Vertebrate Limb by Signals and Growth

[Report] Initiation of Proximal-Distal Patterning in the Vertebrate Limb by Signals and Growth: "Growth of limb cells in culture conditions with subsequent in vivo transplantation allows the dissection of limb patterning.

Authors: Kimberly L. Cooper, Jimmy Kuang-Hsien Hu, Derk ten Berge, Marian Fernandez-Teran, Maria A. Ros, Clifford J. Tabin"

Review. Origin of the fittest

Review. Origin of the fittest: "

In complex organisms, neutral evolution of genomic architecture, associated compensatory interactions in protein networks and emergent developmental processes can delineate the directions of evolutionary change, including the opportunity for natural selection. These effects are reflected in the evolution of developmental programmes that link genomic architecture with a corresponding functioning phenotype. Two recent findings call for closer examination of the rules by which these links are constructed. First is the realization that high dimensionality of genotypes and emergent properties of autonomous developmental processes (such as capacity for self-organization) result in the vast areas of fitness neutrality at both the phenotypic and genetic levels. Second is the ubiquity of context- and taxa-specific regulation of deeply conserved gene networks, such that exceptional phenotypic diversification coexists with remarkably conserved generative processes. Establishing the causal reciprocal links between ongoing neutral expansion of genomic architecture, emergent features of organisms' functionality, and often precisely adaptive phenotypic diversification therefore becomes an important goal of evolutionary biology and is the latest reincarnation of the search for a framework that links development, functioning and evolution of phenotypes. Here I examine, in the light of recent empirical advances, two evolutionary concepts that are central to this framework—natural selection and inheritance—the general rules by which they become associated with emergent developmental and homeostatic processes and the role that they play in descent with modification.

"

[Report] A Packing Mechanism for Nucleosome Organization Reconstituted Across a Eukaryotic Genome

[Report] A Packing Mechanism for Nucleosome Organization Reconstituted Across a Eukaryotic Genome: "Genome-wide nucleosome positioning is a self-organizing system amenable to in vitro reconstitution.

Authors: Zhenhai Zhang, Christian J. Wippo, Megha Wal, Elissa Ward, Philipp Korber, B. Franklin Pugh"

[Report] Chromatin “Prepattern” and Histone Modifiers in a Fate Choice for Liver and Pancreas

[Report] Chromatin “Prepattern” and Histone Modifiers in a Fate Choice for Liver and Pancreas: "Screening histone modifications reveals distinctive patterns of chromatin marks for liver and pancreas development.

Authors: Cheng-Ran Xu, Philip A. Cole, David J. Meyers, Jay Kormish, Sharon Dent, Kenneth S. Zaret"

[Report] Industrial Melanism in British Peppered Moths Has a Singular and Recent Mutational Origin

[Report] Industrial Melanism in British Peppered Moths Has a Singular and Recent Mutational Origin: "The locus responsible for the dark form of the peppered moth is identified.

Authors: Arjen E. van’t Hof, Nicola Edmonds, Martina Dalíková, František Marec, Ilik J. Saccheri"

[Research Article] Comparative Functional Genomics of the Fission Yeasts

[Research Article] Comparative Functional Genomics of the Fission Yeasts: "A combined analysis of genome sequence, structure, and expression gives insights into fission yeast biology.

Authors: Nicholas Rhind, Zehua Chen, Moran Yassour, Dawn A. Thompson, Brian J. Haas, Naomi Habib, Ilan Wapinski, Sushmita Roy, Michael F. Lin, David I. Heiman, Sarah K. Young, Kanji Furuya, Yabin Guo, Alison Pidoux, Huei Mei Chen, Barbara Robbertse, Jonathan M. Goldberg, Keita Aoki, Elizabeth H. Bayne, Aaron M. Berlin, Christopher A. Desjardins, Edward Dobbs, Livio Dukaj, Lin Fan, Michael G. FitzGerald, Courtney French, Sharvari Gujja, Klavs Hansen, Dan Keifenheim, Joshua Z. Levin, Rebecca A. Mosher, Carolin A. Müller, Jenna Pfiffner, Margaret Priest, Carsten Russ, Agata Smialowska, Peter Swoboda, Sean M. Sykes, Matthew Vaughn, Sonya Vengrova, Ryan Yoder, Qiandong Zeng, Robin Allshire, David Baulcombe, Bruce W. Birren, William Brown, Karl Ekwall, Manolis Kellis, Janet Leatherwood, Henry Levin, Hanah Margalit, Rob Martienssen, Conrad A. Nieduszynski, Joseph W. Spatafora, Nir Friedman, Jacob Z. Dalgaard, Peter Baumann, Hironori Niki, Aviv Regev, Chad Nusbaum"

[Research Article] Comparative Functional Genomics of the Fission Yeasts

[Research Article] Comparative Functional Genomics of the Fission Yeasts: "A combined analysis of genome sequence, structure, and expression gives insights into fission yeast biology.

Authors: Nicholas Rhind, Zehua Chen, Moran Yassour, Dawn A. Thompson, Brian J. Haas, Naomi Habib, Ilan Wapinski, Sushmita Roy, Michael F. Lin, David I. Heiman, Sarah K. Young, Kanji Furuya, Yabin Guo, Alison Pidoux, Huei Mei Chen, Barbara Robbertse, Jonathan M. Goldberg, Keita Aoki, Elizabeth H. Bayne, Aaron M. Berlin, Christopher A. Desjardins, Edward Dobbs, Livio Dukaj, Lin Fan, Michael G. FitzGerald, Courtney French, Sharvari Gujja, Klavs Hansen, Dan Keifenheim, Joshua Z. Levin, Rebecca A. Mosher, Carolin A. Müller, Jenna Pfiffner, Margaret Priest, Carsten Russ, Agata Smialowska, Peter Swoboda, Sean M. Sykes, Matthew Vaughn, Sonya Vengrova, Ryan Yoder, Qiandong Zeng, Robin Allshire, David Baulcombe, Bruce W. Birren, William Brown, Karl Ekwall, Manolis Kellis, Janet Leatherwood, Henry Levin, Hanah Margalit, Rob Martienssen, Conrad A. Nieduszynski, Joseph W. Spatafora, Nir Friedman, Jacob Z. Dalgaard, Peter Baumann, Hironori Niki, Aviv Regev, Chad Nusbaum"

The identification of transcription factors expressed in the notochord of Ciona intestinalis adds new potential players to the brachyury gene regulatory network

The identification of transcription factors expressed in the notochord of Ciona intestinalis adds new potential players to the brachyury gene regulatory network: "

Abstract

The notochord is the distinctive characteristic of chordates; however, the knowledge of the complement of transcription factors governing the development of this structure is still incomplete. Here we present the expression patterns of seven transcription factor genes detected in the notochord of the ascidian Ciona intestinalis at various stages of embryonic development. Four of these transcription factors, Fos-a, NFAT5, AFF and Klf15, have not been directly associated with the notochord in previous studies, while the others, including Spalt-like-a, Lmx-like, and STAT5/6-b, display evolutionarily conserved expression in this structure as well as in other domains. We examined the hierarchical relationships between these genes and the transcription factor Brachyury, which is necessary for notochord development in all chordates. We found that Ciona Brachyury regulates the expression of most, although not all, of these genes. These results shed light on the genetic regulatory program underlying notochord formation in Ciona and possibly other chordates. Developmental Dynamics, 2011. © 2011 Wiley-Liss, Inc.

"

Global quantification of mammalian gene expression control

Global quantification of mammalian gene expression control: "

Global quantification of mammalian gene expression control

Nature 473, 7347 (2011). doi:10.1038/nature10098

Authors: Björn Schwanhäusser, Dorothea Busse, Na Li, Gunnar Dittmar, Johannes Schuchhardt, Jana Wolf, Wei Chen & Matthias Selbach

Gene expression is a multistep process that involves the transcription, translation and turnover of messenger RNAs and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute

"

Ugandan Chimpanzees May Be Hunting Red Colobus Monkeys into Extinction

Ugandan Chimpanzees May Be Hunting Red Colobus Monkeys into Extinction: "

Red colobus monkeys in Uganda's Kibale National Park are being hunted to extinction--by chimpanzees. According to a study published May 9 in the American Journal of Primatology , this is the first documented case of a nonhuman primate significantly overhunting another primate species. [More]

"

A synthetic homing endonuclease-based gene drive system in the human malaria mosquito

A synthetic homing endonuclease-based gene drive system in the human malaria mosquito: "

A synthetic homing endonuclease-based gene drive system in the human malaria mosquito

Nature 473, 7346 (2011). doi:10.1038/nature09937

Authors: Nikolai Windbichler, Miriam Menichelli, Philippos Aris Papathanos, Summer B. Thyme, Hui Li, Umut Y. Ulge, Blake T. Hovde, David Baker, Raymond J. Monnat, Austin Burt & Andrea Crisanti

Genetic methods of manipulating or eradicating disease vector populations have long been discussed as an attractive alternative to existing control measures because of their potential advantages in terms of effectiveness and species specificity. The development of genetically engineered malaria-resistant mosquitoes has shown, as a proof of principle, the possibility of targeting the mosquito’s ability to serve as a disease vector. The translation of these achievements into control measures requires an effective technology to spread a genetic modification from laboratory mosquitoes to field populations. We have suggested previously that homing endonuclease genes (HEGs), a class of simple selfish genetic elements, could be exploited for this purpose. Here we demonstrate that a synthetic genetic element, consisting of mosquito regulatory regions and the homing endonuclease gene I-SceI, can substantially increase its transmission to the progeny in transgenic mosquitoes of the human malaria vector Anopheles gambiae. We show that the I-SceI element is able to invade receptive mosquito cage populations rapidly, validating mathematical models for the transmission dynamics of HEGs. Molecular analyses confirm that expression of I-SceI in the male germline induces high rates of site-specific chromosomal cleavage and gene conversion, which results in the gain of the I-SceI gene, and underlies the observed genetic drive. These findings demonstrate a new mechanism by which genetic control measures can be implemented. Our results also show in principle how sequence-specific genetic drive elements like HEGs could be used to take the step from the genetic engineering of individuals to the genetic engineering of populations.

"

Transcriptional Regulation: Effects of Promoter Proximal Pausing on Speed, Synchrony and Reliability

Transcriptional Regulation: Effects of Promoter Proximal Pausing on Speed, Synchrony and Reliability: "

by Alistair N. Boettiger, Peter L. Ralph, Steven N. Evans

Recent whole genome polymerase binding assays in the Drosophila embryo have shown that a substantial proportion of uninduced genes have pre-assembled RNA polymerase-II transcription initiation complex (PIC) bound to their promoters. These constitute a subset of promoter proximally paused genes for which mRNA elongation instead of promoter access is regulated. This difference can be described as a rearrangement of the regulatory topology to control the downstream transcriptional process of elongation rather than the upstream transcriptional initiation event. It has been shown experimentally that genes with the former mode of regulation tend to induce faster and more synchronously, and that promoter-proximal pausing is observed mainly in metazoans, in accord with a posited impact on synchrony. However, it has not been shown whether or not it is the change in the regulated step per se that is causal. We investigate this question by proposing and analyzing a continuous-time Markov chain model of PIC assembly regulated at one of two steps: initial polymerase association with DNA, or release from a paused, transcribing state. Our analysis demonstrates that, over a wide range of physical parameters, increased speed and synchrony are functional consequences of elongation control. Further, we make new predictions about the effect of elongation regulation on the consistent control of total transcript number between cells. We also identify which elements in the transcription induction pathway are most sensitive to molecular noise and thus possibly the most evolutionarily constrained. Our methods produce symbolic expressions for quantities of interest with reasonable computational effort and they can be used to explore the interplay between interaction topology and molecular noise in a broader class of biochemical networks. We provide general-purpose code implementing these methods."

Experimental illumination of a fitness landscape [Genetics]

Experimental illumination of a fitness landscape [Genetics]: "The genes of all organisms have been shaped by selective pressures. The relationship between gene sequence and fitness has tremendous implications for understanding both evolutionary processes and functional constraints on the encoded proteins. Here, we have exploited deep sequencing technology to experimentally determine the fitness of all possible individual point mutants under controlled conditions for a nine-amino acid region of Hsp90. Over the past five decades, limited glimpses into the relationship between gene sequence and function have sparked a long debate regarding the distribution, relative proportion, and evolutionary significance of deleterious, neutral, and advantageous mutations. Our systematic experimental measurement of fitness effects of Hsp90 mutants in yeast, evaluated in the light of existing population genetic theory, are remarkably consistent with a nearly neutral model of molecular evolution."

Postmating transcriptional changes in reproductive tracts of con- and heterospecifically mated Drosophila mojavensis females [Evolution]

Postmating transcriptional changes in reproductive tracts of con- and heterospecifically mated Drosophila mojavensis females [Evolution]: "In internally fertilizing organisms, mating involves a series of highly coordinated molecular interactions between the sexes that occur within the female reproductive tract. In species where females mate multiply, traits involved in postcopulatory interactions are expected to evolve rapidly, potentially leading to postmating-prezygotic (PMPZ) reproductive isolation between diverging populations. Here, we investigate the postmating transcriptional response of the lower reproductive tract of Drosophila mojavensis females following copulation with either conspecific or heterospecific (Drosophila arizonae) males at three time points postmating. Relatively few genes (15 total) were differentially regulated in the female lower reproductive tract in response to conspecific mating. Heterospecifically mated females exhibited significant perturbations in the expression of the majority of these genes, and also down-regulated transcription of a number of others, including several involved in mitochondrial function. These striking regulatory differences indicate failed postcopulatory molecular interactions between the sexes consistent with the strong PMPZ isolation observed for this cross. We also report the transfer of male accessory-gland protein (Acp) transcripts from males to females during copulation, a finding with potentially broad implications for understanding postcopulatory molecular interactions between the sexes."

Dynamic reprogramming of chromatin accessibility during Drosophila embryo development

Dynamic reprogramming of chromatin accessibility during Drosophila embryo development: "Background:
The development of complex organisms is believed to involve progressive restrictions in cellular fate. Understanding the scope and features of chromatin dynamics during embryogenesis, and identifying regulatory elements important for directing developmental processes remain key goals of developmental biology.
Results:
We used in vivo DNaseI sensitivity to map the locations of regulatory elements, and explore the changing chromatin landscape during the first 11 hours of Drosophila embryonic development. We identified thousands of conserved, developmentally dynamic, distal DNaseI hypersensitive sites associated with spatial and temporal expression patterning of linked genes and with large regions of chromatin plasticity. We observed a nearly uniform balance between developmentally up- and down-regulated DNaseI hypersensitive sites. Analysis of promoter chromatin architecture revealed a novel role for classical core promoter sequence elements in directing temporally-regulated chromatin remodeling. Another unexpected feature of the chromatin landscape was the presence of localized accessibility over many protein-coding regions, subsets of which were developmentally regulated or associated with the transcription of genes with prominent maternal RNA contributions in the blastoderm.
Conclusions:
Our results provide a global view of the rich and dynamic chromatin landscape of early animal development, as well as novel insights into the organization of developmentally regulated chromatin features."

CpG islands and the regulation of transcription [Reviews]

CpG islands and the regulation of transcription [Reviews]: "

Vertebrate CpG islands (CGIs) are short interspersed DNA sequences that deviate significantly from the average genomic pattern by being GC-rich, CpG-rich, and predominantly nonmethylated. Most, perhaps all, CGIs are sites of transcription initiation, including thousands that are remote from currently annotated promoters. Shared DNA sequence features adapt CGIs for promoter function by destabilizing nucleosomes and attracting proteins that create a transcriptionally permissive chromatin state. Silencing of CGI promoters is achieved through dense CpG methylation or polycomb recruitment, again using their distinctive DNA sequence composition. CGIs are therefore generically equipped to influence local chromatin structure and simplify regulation of gene activity.

"

Paused RNA Polymerase II as a Developmental Checkpoint

Paused RNA Polymerase II as a Developmental Checkpoint: "Michael Levine. The textbook view of gene activation is that the rate-limiting step is the interaction of RNA polymerase II (Pol II) with the gene's promoter. However, studies in a variety of systems, including h...."

An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation

An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation: "

An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation

Nature Communications 2, 310 (2011). doi:10.1038/ncomms1301

Authors: Juan J. Tena, M. Eva Alonso, Elisa de la Calle-Mustienes, Erik Splinter, Wouter de Laat, Miguel Manzanares & José Luis Gómez-Skarmeta

"

Parallel evolution of the make–accumulate–consume strategy in Saccharomyces and Dekkera yeasts

Parallel evolution of the make–accumulate–consume strategy in Saccharomyces and Dekkera yeasts: "

Parallel evolution of the make–accumulate–consume strategy in Saccharomyces and Dekkera yeasts

Nature Communications 2, 302 (2011). doi:10.1038/ncomms1305

Authors: Elżbieta Rozpędowska, Linda Hellborg, Olena P. Ishchuk, Furkan Orhan, Silvia Galafassi, Annamaria Merico, Megan Woolfit, Concetta Compagno & Jure Piškur

"

Selection for evolvability

Selection for evolvability: "

A basic assumption of the Darwinian theory of evolution is that heritable variation arises randomly. In this context, randomness means that mutations arise irrespective of the current adaptive needs imposed by the environment. It is broadly accepted, however, that phenotypic variation is not uniformly distributed among phenotypic traits, some traits tend to covary, while others vary independently, and again others barely vary at all. Furthermore, it is well established that patterns of trait variation differ among species. Specifically, traits that serve different functions tend to be less correlated, as for instance forelimbs and hind limbs in bats and humans, compared with the limbs of quadrupedal mammals. Recently, a novel class of genetic elements has been identified in mouse gene-mapping studies that modify correlations among quantitative traits. These loci are called relationship loci, or relationship Quantitative Trait Loci (rQTL), and affect trait correlations by changing the expression of the existing genetic variation through gene interaction. Here, we present a population genetic model of how natural selection acts on rQTL. Contrary to the usual neo-Darwinian theory, in this model, new heritable phenotypic variation is produced along the selected dimension in response to directional selection. The results predict that selection on rQTL leads to higher correlations among traits that are simultaneously under directional selection. On the other hand, traits that are not simultaneously under directional selection are predicted to evolve lower correlations. These results and the previously demonstrated existence of rQTL variation, show a mechanism by which natural selection can directly enhance the evolvability of complex organisms along lines of adaptive change.

"

Cranial evolution in carnivorous mammals

Cranial evolution in carnivorous mammals: "

Carnivory has evolved independently several times in eutherian (including placental) and metatherian (including marsupial) mammals. We used geometric morphometrics to assess convergences associated with the evolution of carnivory across a broad suite of mammals, including the eutherian clades Carnivora and Creodonta and the metatherian clades Thylacoleonidae, Dasyuromorphia, Didelphidae and Borhyaenoidea. We further quantified cranial disparity across eutherians and metatherians to test the hypothesis that the marsupial mode of reproduction has constrained their morphological evolution. This study, to our knowledge the first to extensively sample pre-Pleistocene taxa, analysed 30 three-dimensional landmarks, focused mainly on the facial region, which were digitized on 130 specimens, including 36 fossil taxa. Data were analysed with principal components (PC) analysis, and three measures of disparity were compared between eutherians and metatherians. PC1 showed a shift from short to long faces and seemed to represent diet and ecology. PC2 was dominated by the unique features of sabre-toothed forms: dramatic expansion of the maxilla at the expense of the frontal bones. PC3, in combination with PC1, distinguished metatherians and eutherians. Metatherians, despite common comparisons with felids, were more similar to caniforms, which was unexpected for taxa such as the sabre-toothed marsupial Thylacosmilus. Contrary to previous studies, metatherian carnivores consistently exhibited disparity which exceeded that of the much more speciose eutherian carnivore radiations, refuting the hypothesis that developmental constraints have limited the morphological evolution of the marsupial cranium.

"

Engrailed homeoprotein acts as a signaling molecule in the developing fly [RESEARCH ARTICLES]

Engrailed homeoprotein acts as a signaling molecule in the developing fly [RESEARCH ARTICLES]: "Sophie Layalle, Michel Volovitch, Bruno Mugat, Nathalie Bonneaud, Marie-Laure Parmentier, Alain Prochiantz, Alain Joliot, and Florence Maschat

Homeodomain transcription factors classically exert their morphogenetic activities through the cell-autonomous regulation of developmental programs. In vertebrates, several homeoproteins have also been shown to have direct non-cell-autonomous activities in the developing nervous system. We present the first in vivo evidence for homeoprotein signaling in Drosophila. Focusing on wing development as a model, we first demonstrate that the homeoprotein Engrailed (En) is secreted. Using single-chain anti-En antibodies expressed under the control of a variety of promoters, we delineate the wing territories in which secreted En acts. We show that En is a short-range signaling molecule that participates in anterior crossvein development, interacting with the Dpp signaling pathway. This report thus suggests that direct signaling with homeoproteins is an evolutionarily conserved phenomenon that is not restricted to neural tissues and involves interactions with bona fide signal transduction pathways.

"

Evolutionary crossroads in developmental biology: the tunicates [PRIMER]

Evolutionary crossroads in developmental biology: the tunicates [PRIMER]: "Patrick Lemaire

The tunicates, or urochordates, constitute a large group of marine animals whose recent common ancestry with vertebrates is reflected in the tadpole-like larvae of most tunicates. Their diversity and key phylogenetic position are enhanced, from a research viewpoint, by anatomically simple and transparent embryos, compact rapidly evolving genomes, and the availability of powerful experimental and computational tools with which to study these organisms. Tunicates are thus a powerful system for exploring chordate evolution and how extreme variation in genome sequence and gene regulatory network architecture is compatible with the preservation of an ancestral chordate body plan.

"

Focusing Transgene Expression in Drosophila by Coupling Gal4 With a Novel Split-LexA Expression System [Methods, technology, and resources]

Focusing Transgene Expression in Drosophila by Coupling Gal4 With a Novel Split-LexA Expression System [Methods, technology, and resources]: "

Here we report the development of a ternary version of the LexA::VP16/LexAop system in which the DNA-binding and trans-activating moieties are independently targeted using distinct promoters to achieve highly restricted, intersectional expression patterns. This Split LexA system can be concatenated with the Gal4/upstream activating sequence system to refine the expression patterns of existing Gal4 lines with minimal genetic manipulations.

"

Body plan innovation in treehoppers through the evolution of an extra wing-like appendage

Body plan innovation in treehoppers through the evolution of an extra wing-like appendage: "

Body plan innovation in treehoppers through the evolution of an extra wing-like appendage

Nature 473, 7345 (2011). doi:10.1038/nature09977

Authors: Benjamin Prud’homme, Caroline Minervino, Mélanie Hocine, Jessica D. Cande, Aïcha Aouane, Héloïse D. Dufour, Victoria A. Kassner & Nicolas Gompel

Body plans, which characterize the anatomical organization of animal groups of high taxonomic rank, often evolve by the reduction or loss of appendages (limbs in vertebrates and legs and wings in insects, for example). In contrast, the addition of new features is extremely rare and is thought to be heavily constrained, although the nature of the constraints remains elusive. Here we show that the treehopper (Membracidae) ‘helmet’ is actually an appendage, a wing serial homologue on the first thoracic segment. This innovation in the insect body plan is an unprecedented situation in 250 Myr of insect evolution. We provide evidence suggesting that the helmet arose by escaping the ancestral repression of wing formation imparted by a member of the Hox gene family, which sculpts the number and pattern of appendages along the body axis. Moreover, we propose that the exceptional morphological diversification of the helmet was possible because, in contrast to the wings, it escaped the stringent functional requirements imposed by flight. This example illustrates how complex morphological structures can arise by the expression of ancestral developmental potentials and fuel the morphological diversification of an evolutionary lineage.

"

Mapping and analysis of chromatin state dynamics in nine human cell types

Mapping and analysis of chromatin state dynamics in nine human cell types: "

Mapping and analysis of chromatin state dynamics in nine human cell types

Nature 473, 7345 (2011). doi:10.1038/nature09906

Authors: Jason Ernst, Pouya Kheradpour, Tarjei S. Mikkelsen, Noam Shoresh, Lucas D. Ward, Charles B. Epstein, Xiaolan Zhang, Li Wang, Robbyn Issner, Michael Coyne, Manching Ku, Timothy Durham, Manolis Kellis & Bradley E. Bernstein

Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine

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Extensive DNA-binding specificity divergence of a conserved transcription regulator [Genetics]

Extensive DNA-binding specificity divergence of a conserved transcription regulator [Genetics]: "The DNA sequence recognized by a transcription regulator can be conserved across large evolutionary distances. For example, it is known that many homologous regulators in yeasts and mammals can recognize the same (or closely related) DNA sequences. In contrast to this paradigm, we describe a case in which the DNA-binding specificity of a transcription regulator has changed so extensively (and over a much smaller evolutionary distance) that its cis-regulatory sequence appears unrelated in different species. Bioinformatic, genetic, and biochemical approaches were used to document and analyze a major change in the DNA-binding specificity of Matα1, a regulator of cell-type specification in ascomycete fungi. Despite this change, Matα1 controls the same core set of genes in the hemiascomycetes because its DNA recognition site has evolved with it, preserving the protein-DNA interaction but significantly changing its molecular details. Matα1 and its recognition sequence diverged most dramatically in the common ancestor of the CTG-clade (Candida albicans, Candida lusitaniae, and related species), apparently without the aid of a gene duplication event. Our findings suggest that DNA-binding specificity divergence between orthologous transcription regulators may be more prevalent than previously thought and that seemingly unrelated cis-regulatory sequences can nonetheless be homologous. These findings have important implications for understanding transcriptional network evolution and for the bioinformatic analysis of regulatory circuits."

Genes involved in convergent evolution of eusociality in bees [Evolution]

Genes involved in convergent evolution of eusociality in bees [Evolution]: "Eusociality has arisen independently at least 11 times in insects. Despite this convergence, there are striking differences among eusocial lifestyles, ranging from species living in small colonies with overt conflict over reproduction to species in which colonies contain hundreds of thousands of highly specialized sterile workers produced by one or a few queens. Although the evolution of eusociality has been intensively studied, the genetic changes involved in the evolution of eusociality are relatively unknown. We examined patterns of molecular evolution across three independent origins of eusociality by sequencing transcriptomes of nine socially diverse bee species and combining these data with genome sequence from the honey bee Apis mellifera to generate orthologous sequence alignments for 3,647 genes. We found a shared set of 212 genes with a molecular signature of accelerated evolution across all eusocial lineages studied, as well as unique sets of 173 and 218 genes with a signature of accelerated evolution specific to either highly or primitively eusocial lineages, respectively. These results demonstrate that convergent evolution can involve a mosaic pattern of molecular changes in both shared and lineage-specific sets of genes. Genes involved in signal transduction, gland development, and carbohydrate metabolism are among the most prominent rapidly evolving genes in eusocial lineages. These findings provide a starting point for linking specific genetic changes to the evolution of eusociality."

Conserved, developmentally regulated mechanism couples chromosomal looping and heterochromatin barrier activity at the homeobox gene A locus [Biochemistry]

Conserved, developmentally regulated mechanism couples chromosomal looping and heterochromatin barrier activity at the homeobox gene A locus [Biochemistry]: "Establishment and segregation of distinct chromatin domains are essential for proper genome function. The insulator protein CCCTC-binding factor (CTCF) is involved in creating boundaries that segregate chromatin and functional domains and in organizing higher-order chromatin structures by promoting chromosomal loops across the vertebrate genome. Here, we investigate the insulation properties of CTCF at the human and mouse homeobox gene A (HOXA) loci. Although cohesin loading at the CTCF binding site is required for looping, we found that cohesin is dispensable for chromatin barrier activity at that site. Using mouse embryonic stem cells in both a pluripotent and differentiated neuronal progenitor state, we determined that embryonic stem cell pluripotency factor OCT4 antagonizes cohesin loading at the CTCF binding site. Loss of OCT4 in the committed and differentiated neuronal progenitor cells results in loading of cohesin and chromosome looping, which contributes to heterochromatin partitioning and selective gene activation across the HOXA locus. Our analysis reveals that chromatin barrier activity of CTCF is evolutionarily conserved and is responsible for the coordinated establishment of chromatin structure, higher-order architecture, and developmental expression of the HOXA locus."

Morphogens, nutrients, and the basis of organ scaling

Morphogens, nutrients, and the basis of organ scaling: "

SUMMARY
The regulation of organ size is a long-standing problem in animal development. Studies in this area have shown that organ-intrinsic patterning morphogens influence organ size, guiding growth in accordance with positional information. However, organ-extrinsic humoral factors such as insulin also affect organ size, synchronizing growth with nutrient levels. Proliferating cells must integrate instructions from morphogens with those from nutrition so that growth proceeds as a function of both inputs. Coordinating cell proliferation with morphogens and nutrients ensures organs scale appropriately with body size, but the basis of this coordination is unclear. Here, the problem is illustrated using the Drosophila wing—a paradigm for organ growth and size control—and a potential solution suggested.

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Molecular paleobiological insights into the origin of the Brachiopoda

Molecular paleobiological insights into the origin of the Brachiopoda: "

SUMMARY

Most studies of brachiopod evolution have been based on their extensive fossil record, but molecular techniques, due to their independence from the rock record, can offer new insights into the evolution of a clade. Previous molecular phylogenetic hypotheses of brachiopod interrelationships place phoronids within the brachiopods as the sister group to the inarticulates, whereas morphological considerations suggest that Brachiopoda is a monophyletic group. Here, these hypotheses were tested with a molecular phylogenetic analysis of seven nuclear housekeeping genes combined with three ribosomal genes. The combined analysis finds brachiopods to be monophyletic, but with relatively weak support, and the craniid as the sister taxon of all other brachiopods. Phylogenetic-signal dissection suggests that the weak support is caused by the instability of the craniid, which is attracted to the phoronids. Analysis of slowly evolving sites results in a robustly supported monophyletic Brachiopoda and Inarticulata (Linguliformea+Craniiformea), which is regarded as the most likely topology for brachiopod interrelationships. The monophyly of Brachiopoda was further tested with microRNA-based phylogenetics, which are small, noncoding RNA genes whose presence and absence can be used to infer phylogenetic relationships. Two novel microRNAs were characterized supporting the monophyly of brachiopods. Congruence of the traditional molecular phylogenetic analysis, microRNAs, and morphological cladograms suggest that Brachiopoda is monophyletic with Phoronida as its likely sister group. Molecular clock analysis suggests that extant phoronids have a Paleozoic divergence despite their conservative morphology, and that the early brachiopod fossil record is robust, and is not affected by taphonomic factors relating to the late-Precambrian/early-Cambrian phosphogenic event.

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Finding the frame shift: digit loss, developmental variability, and the origin of the avian hand

Finding the frame shift: digit loss, developmental variability, and the origin of the avian hand: "

SUMMARY
The origin of the tridactyl hand of crown birds from the pentadactyl hand of those early theropod dinosaurs lying along the avian stem has become a classic, but at times seemingly intractable, historical problem. The point in question is whether the fingers of crown birds represent digits 1–3 as predicted by generalized trends in the fossil record; or digits 2–4, as evidenced by the topology of the embryonic mesenchymal condensations from which the digits develop. The frame shift hypothesis attempted to resolve this paradox by making these signals congruent by means of a homeotic transformation in digital identity, but recently the paleontological support for this hypothesis was questioned. Here, we reassess the frame shift from a paleontological perspective by addressing what predictions a frame shift makes for skeletal morphology, whether the frame shift remains a viable explanation of the known fossil data, and where on the theropod tree the frame shift most likely occurred. Our results indicate that the frame shift remains viable, and based on the inferred pattern of digit loss, the frame shift likely occurred at a deeper position in theropod phylogeny than previously proposed. A new evolutionary model of the frame shift is described in which the early history of the frame-shifted hand is marked by an extended zone of developmental polymorphism. This model provides a new conceptual framework for the role of developmental variability in communicating broad evolutionary patterns on a taxonomically inclusive phylogenetic tree.

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Does Positive Selection Drive Transcription Factor Binding Site Turnover? A Test with Drosophila Cis-Regulatory Modules

Does Positive Selection Drive Transcription Factor Binding Site<br> Turnover? A Test with Drosophila Cis-Regulatory Modules: "
by Bin Z. He, Alisha K. Holloway, Sebastian J. Maerkl, Martin Kreitman


Transcription factor binding site(s) (TFBS) gain and loss (i.e., turnover) is a
well-documented feature of cis-regulatory module (CRM) evolution, yet little
attention has been paid to the evolutionary force(s) driving this turnover
process. The predominant view, motivated by its widespread occurrence,
emphasizes the importance of compensatory mutation and genetic drift. Positive
selection, in contrast, although it has been invoked in specific instances of
adaptive gene expression evolution, has not been considered as a general
alternative to neutral compensatory evolution. In this study we evaluate the two
hypotheses by analyzing patterns of single nucleotide polymorphism in the TFBS
of well-characterized CRM in two closely related Drosophila species,
Drosophila melanogaster and Drosophila
simulans. An important feature of the analysis is classification of
TFBS mutations according to the direction of their predicted effect on binding
affinity, which allows gains and losses to be evaluated independently along the
two phylogenetic lineages. The observed patterns of polymorphism and divergence
are not compatible with neutral evolution for either class of mutations.
Instead, multiple lines of evidence are consistent with contributions of
positive selection to TFBS gain and loss as well as purifying selection in its
maintenance. In discussion, we propose a model to reconcile the finding of
selection driving TFBS turnover with constrained CRM function over long
evolutionary time."

Genetic architecture of regulatory variation in Arabidopsis thaliana [RESEARCH]

Genetic architecture of regulatory variation in Arabidopsis thaliana [RESEARCH]: "

Studying the genetic regulation of expression variation is a key method to dissect complex phenotypic traits. To examine the genetic architecture of regulatory variation in Arabidopsis thaliana, we performed genome-wide association (GWA) mapping of gene expression in an F₁ hybrid diversity panel. At a genome-wide false discovery rate (FDR) of 0.2, an associated single nucleotide polymorphism (SNP) explains >38% of trait variation. In comparison with SNPs that are distant from the genes to which they were associated, locally associated SNPs are preferentially found in regions with extended linkage disequilibrium (LD) and have distinct population frequencies of the derived alleles (where Arabidopsis lyrata has the ancestral allele), suggesting that different selective forces are acting. Locally associated SNPs tend to have additive inheritance, whereas distantly associated SNPs are primarily dominant. In contrast to results from mapping of expression quantitative trait loci (eQTL) in linkage studies, we observe extensive allelic heterogeneity for local regulatory loci in our diversity panel. By association mapping of allele-specific expression (ASE), we detect a significant enrichment for cis-acting variation in local regulatory variation. In addition to gene expression variation, association mapping of splicing variation reveals both local and distant genetic regulation for intron and exon level traits. Finally, we identify candidate genes for 59 diverse phenotypic traits that were mapped to eQTL.

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Nucleosome fragility reveals novel functional states of chromatin and poises genes for activation [RESEARCH]

Nucleosome fragility reveals novel functional states of chromatin and poises genes for activation [RESEARCH]: "

The structural complexity of nucleosomes underlies their functional versatility. Here we report a new type of complexity—nucleosome fragility, manifested as high sensitivity to micrococcal nuclease, in contrast to the common presumption that nucleosomes are similar in resistance to MNase digestion. Using differential MNase digestion of chromatin and high-throughput sequencing, we have identified a special group of nucleosomes termed "fragile nucleosomes" throughout the yeast genome, nearly 1000 of which were at previously determined "nucleosome-free" loci. Nucleosome fragility is broadly implicated in multiple chromatin processes, including transcription, translocation, and replication, in correspondence to specific physiological states of cells. In the environmental-stress-response genes, the presence of fragile nucleosomes prior to the occurrence of environmental changes suggests that nucleosome fragility poises genes for swift up-regulation in response to the environmental changes. We propose that nucleosome fragility underscores distinct functional statuses of the chromatin and provides a new dimension for portraying the landscape of genome organization.

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Core promoter T-blocks correlate with gene expression levels in C. elegans [RESEARCH]

Core promoter T-blocks correlate with gene expression levels in C. elegans [RESEARCH]: "

Core promoters mediate transcription initiation by the integration of diverse regulatory signals encoded in the proximal promoter and enhancers. It has been suggested that genes under simple regulation may have low-complexity permissive promoters. For these genes, the core promoter may serve as the principal regulatory element; however, the mechanism by which this occurs is unclear. We report here a periodic poly-thymine motif, which we term T-blocks, enriched in occurrences within core promoter forward strands in Caenorhabditis elegans. An increasing number of T-blocks on either strand is associated with increasing nucleosome eviction. Strikingly, only forward strand T-blocks are correlated with expression levels, whereby genes with ≥6 T-blocks have fivefold higher expression levels than genes with ≤3 T-blocks. We further demonstrate that differences in T-block numbers between strains predictably affect expression levels of orthologs. Highly expressed genes and genes in operons tend to have a large number of T-blocks, as well as the previously characterized SL1 motif involved in trans-splicing. The presence of T-blocks thus correlates with low nucleosome occupancy and the precision of a trans-splicing motif, suggesting its role at both the DNA and RNA levels. Collectively, our results suggest that core promoters may tune gene expression levels through the occurrences of T-blocks, independently of the spatio-temporal regulation mediated by the proximal promoter.

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Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements [RESEARCH]

Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements [RESEARCH]: "

The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. Contradicting results have been reported to date, with little consensus about the dynamics of nuclear organization and the features of the contact loci. In this study, we investigated the properties and dynamics of genomic loci that are in contact with glucocorticoid receptor (GR)–responsive loci. We took a systematic approach, combining genome-wide interaction profiling by the chromosome conformation capture on chip (4C) technology with expression, protein occupancy, and chromatin accessibility profiles. This approach allowed a comprehensive analysis of how distinct features of the linear genome are organized in the three-dimensional nuclear space in the context of rapid gene regulation. We found that the transcriptional response to GR occurs without dramatic nuclear reorganization. Moreover, contrary to the view of transcription-driven organization, even genes with opposite transcriptional responses colocalize. Regions contacting GR-regulated genes are not particularly enriched for GR-regulated loci or for any functional group of genes, suggesting that these subnuclear environments are not organized to respond to a specific factor. The contact regions are, however, highly enriched for DNase I–hypersensitive sites that comprehensively mark cell-type–specific regulatory sites. These findings indicate that the nucleus is pre-organized in a conformation allowing rapid transcriptional reprogramming, and this organization is significantly correlated with cell-type–specific chromatin sites accessible to regulatory factors. Numerous open chromatin loci may be arranged in nuclear domains that are poised to respond to diverse signals in general and to permit efficient gene regulation.

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Transcriptional Coupling of Neighboring Genes and Gene Expression Noise: Evidence that Gene Orientation and Noncoding Transcripts Are Modulators of Noise

Transcriptional Coupling of Neighboring Genes and Gene Expression Noise: Evidence that Gene Orientation and Noncoding Transcripts Are Modulators of Noise: "

How is noise in gene expression modulated? Do mechanisms of noise control impact genome organization? In yeast, the expression of one gene can affect that of a very close neighbor. As the effect is highly regionalized, we hypothesize that genes in different orientations will have differing degrees of coupled expression and, in turn, different noise levels. Divergently organized gene pairs, in particular those with bidirectional promoters, have close promoters, maximizing the likelihood that expression of one gene affects the neighbor. With more distant promoters, the same is less likely to hold for gene pairs in nondivergent orientation. Stochastic models suggest that coupled chromatin dynamics will typically result in low abundance-corrected noise (ACN). Transcription of noncoding RNA (ncRNA) from a bidirectional promoter, we thus hypothesize to be a noise-reduction, expression-priming, mechanism. The hypothesis correctly predicts that protein-coding genes with a bidirectional promoter, including those with a ncRNA partner, have lower ACN than other genes and divergent gene pairs uniquely have correlated ACN. Moreover, as predicted, ACN increases with the distance between promoters. The model also correctly predicts ncRNA transcripts to be often divergently transcribed from genes that a priori would be under selection for low noise (essential genes, protein complex genes) and that the latter genes should commonly reside in divergent orientation. Likewise, that genes with bidirectional promoters are rare subtelomerically, cluster together, and are enriched in essential gene clusters is expected and observed. We conclude that gene orientation and transcription of ncRNAs are candidate modulators of noise.

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Parallel evolution controlled by adaptation and covariation in ammonoid cephalopods

Parallel evolution controlled by adaptation and covariation in ammonoid cephalopods: "Background:
A major goal in evolutionary biology is to understand the processes that shape the evolutionary trajectory of clades. The repeated and similar large-scale morphological evolutionary trends of distinct lineages suggest that adaptation by means of natural selection (functional constraints) is the major cause of parallel evolution, a very common phenomenon in extinct and extant lineages. However, parallel evolution can result from other processes, which are usually ignored or difficult to identify, such as developmental constraints. Hence, understanding the underlying processes of parallel evolution still requires further research.
Results:
Herein, we present a possible case of parallel evolution between two ammonoid lineages (Auguritidae and Pinacitidae) of Early-Middle Devonian age (405-395 Ma), which are extinct cephalopods with an external, chambered shell. In time and through phylogenetic order of appearance, both lineages display a morphological shift toward more involute coiling (i.e. more tightly coiled whorls), larger adult body size, more complex suture line (the folded walls separating the gas-filled buoyancy-chambers), and the development of an umbilical lid (a very peculiar extension of the lateral shell wall covering the umbilicus) in the most derived taxa. Increased involution toward shells with closed umbilicus has been demonstrated to reflect improved hydrodynamic properties of the shell and thus likely results from similar natural selection pressures. The peculiar umbilical lid might have also added to the improvement of the hydrodynamic properties of the shell. Finally, increasing complexity of suture lines likely results from covariation induced by trends of increasing adult size and whorl overlap given the morphogenetic properties of the suture.
Conclusions:
The morphological evolution of these two Devonian ammonoid lineages follows a near parallel evolutionary path for some important shell characters during several million years and through their phylogeny. Evolution of some traits (involution, umbilical lid) appears to be mainly driven by adaptation to improve the hydrodynamic properties of the shell, whereas other characters (sutural complexity) evolved due to covariation with features that play a central role in the morphogenesis of mollusc shells. This example provides evidence that parallel evolution can be driven simultaneously by different factors such as covariation (constructional constraints) and adaptation (natural selection)."

A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets [Research Papers]

A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets [Research Papers]: "

Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural genes activate neurogenesis—and, in particular, the genes that they regulate—however, are mostly unknown. We performed a genome-wide characterization of the transcriptional targets of Ascl1 in the embryonic brain and in neural stem cell cultures by location analysis and expression profiling of embryos overexpressing or mutant for Ascl1. The wide range of molecular and cellular functions represented among these targets suggests that Ascl1 directly controls the specification of neural progenitors as well as the later steps of neuronal differentiation and neurite outgrowth. Surprisingly, Ascl1 also regulates the expression of a large number of genes involved in cell cycle progression, including canonical cell cycle regulators and oncogenic transcription factors. Mutational analysis in the embryonic brain and manipulation of Ascl1 activity in neural stem cell cultures revealed that Ascl1 is indeed required for normal proliferation of neural progenitors. This study identified a novel and unexpected activity of the proneural gene Ascl1, and revealed a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation.

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