PU.1 and C/EBP{alpha} synergistically program distinct response to NF-{kappa}B activation through establishing monocyte specific enhancers [Cell Biology]

PU.1 and C/EBP{alpha} synergistically program distinct response to NF-{kappa}B activation through establishing monocyte specific enhancers [Cell Biology]: "Unraveling the complexity of transcriptional programs coded by different cell types has been one of the central goals of cell biology. By using genome-wide location analysis, we examined how two different cell types generate different responses to the NF-κB signaling pathway. We showed that, after TNF-α treatment, the NF-κB p65 subunit binds to distinct genome locations and subsequently induces different subsets of genes in human monocytic THP-1 cells versus HeLa cells. Interestingly, the differential p65 binding in two cell types correlates with preexisting cell type-specific enhancers before TNF-α stimulation, marked by histone modifications. We also found that two transcription factors, PU.1 and C/EBPα, appear to synergistically mediate enhancer creation and affect NF-κB target selection in THP-1 cells. In HeLa cells, coexpression of PU.1 and C/EBPα conferred TNF-α responsiveness to a subset of THP-1–specific NF-κB target genes. These results suggest that the diversity of transcriptional programs in mammalian cells arises, at least in part, from preexisting enhancers that are established by cell-specific transcription factors."

Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor

Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor: "

Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor

Nature Genetics 43, 379 (2011).
doi:10.1038/ng.790

Authors: Sandra Ruf, Orsolya Symmons, Veli Vural Uslu, Dirk Dolle, Chloé Hot, Laurence Ettwiller & François Spitz

"

The dawn of beer remains elusive in archaeological record

The dawn of beer remains elusive in archaeological record: "

NEW YORK CITY--Who brewed--and then enjoyed--the first beer? The civilization responsible for the widely beloved beverage must have been a very old one, but we don't yet know who first brewed up a batch of beer, Christine Hastorf explained in a March 10 lecture at New York University on the archaeology of beer. [More]

"

Interactions among Polycomb Domains Are Guided by Chromosome Architecture

Interactions among Polycomb Domains Are Guided by Chromosome Architecture: "Author Summary

The folding of chromosomes inside the cell nucleus is a fascinating yet poorly understood topological problem. It is thought that certain genomic loci that are distant in the linear genome may come together in nuclear space by folding of the chromosome fiber. Previously, such a long-range interaction was found in Drosophila for two genomic loci that are known to be bound by the Polycomb Repressive Complex. Because hundreds of genes are known to be bound by Polycomb proteins, we asked whether such long-range contacts are more common. To address this, we optimized the Chromosome Conformation Capture on Chip (4C) technology for use in small tissue samples. Using this technique in dissected larval brains, we found that indeed Polycomb target genes interact frequently with each other, even when they are separated by megabases of sequence. However, these long-range interactions occur almost exclusively on the same chromosome arm. By using a rearranged chromosome in which segments are swapped between two arms, we demonstrate that not DNA sequence but chromosome architecture imposes this restriction. Taken together, our data demonstrate that Polycomb target genes extensively interact in nuclear space, but only when they are located on the same chromosome arm.

"

An Early Cambrian Hemichordate Zooid

An Early Cambrian Hemichordate Zooid: "Xian-guang Hou, Richard J. Aldridge, David J. Siveter, Derek J. Siveter, Mark Williams, Jan Zalasiewicz, Xiao-ya Ma. Hemichordates are known as fossils from at least the earliest mid-Cambrian Period (ca. 510 Ma) and are well represented in the fossil record by the graptolithinid pterobranchs (“graptolites”), whi...."

A cis-regulatory map of the Drosophila genome

A cis-regulatory map of the Drosophila genome: "

A cis-regulatory map of the Drosophila genome

Nature 471, 7339 (2011). doi:10.1038/nature09990

Authors: Nicolas Nègre, Christopher D. Brown, Lijia Ma, Christopher Aaron Bristow, Steven W. Miller, Ulrich Wagner, Pouya Kheradpour, Matthew L. Eaton, Paul Loriaux, Rachel Sealfon, Zirong Li, Haruhiko Ishii, Rebecca F. Spokony, Jia Chen, Lindsay Hwang, Chao Cheng, Richard P. Auburn, Melissa B. Davis, Marc Domanus, Parantu K. Shah, Carolyn A. Morrison, Jennifer Zieba, Sarah Suchy, Lionel Senderowicz, Alec Victorsen, Nicholas A. Bild, A. Jason Grundstad, David Hanley, David M. MacAlpine, Mattias Mannervik, Koen Venken, Hugo Bellen, Robert White, Mark Gerstein, Steven Russell, Robert L. Grossman, Bing Ren, James W. Posakony, Manolis Kellis & Kevin P. White

Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide has successfully identified specific subtypes of regulatory elements. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements, chromatin states, transcription factor binding sites, RNA polymerase II regulation and insulator elements; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships.

"

The developmental transcriptome of Drosophila melanogaster

The developmental transcriptome of Drosophila melanogaster: "

The developmental transcriptome of Drosophila melanogaster

Nature 471, 7339 (2011). doi:10.1038/nature09715

Authors: Brenton R. Graveley, Angela N. Brooks, Joseph W. Carlson, Michael O. Duff, Jane M. Landolin, Li Yang, Carlo G. Artieri, Marijke J. van Baren, Nathan Boley, Benjamin W. Booth, James B. Brown, Lucy Cherbas, Carrie A. Davis, Alex Dobin, Renhua Li, Wei Lin, John H. Malone, Nicolas R. Mattiuzzo, David Miller, David Sturgill, Brian B. Tuch, Chris Zaleski, Dayu Zhang, Marco Blanchette, Sandrine Dudoit, Brian Eads, Richard E. Green, Ann Hammonds, Lichun Jiang, Phil Kapranov, Laura Langton, Norbert Perrimon, Jeremy E. Sandler, Kenneth H. Wan, Aarron Willingham, Yu Zhang, Yi Zou, Justen Andrews, Peter J. Bickel, Steven E. Brenner, Michael R. Brent, Peter Cherbas, Thomas R. Gingeras, Roger A. Hoskins, Thomas C. Kaufman, Brian Oliver & Susan E. Celniker

Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA

"

Comprehensive analysis of the chromatin landscape in Drosophila melanogaster

Comprehensive analysis of the chromatin landscape in Drosophila melanogaster: "

Comprehensive analysis of the chromatin landscape in Drosophila melanogaster

Nature 471, 7339 (2011). doi:10.1038/nature09725

Authors: Peter V. Kharchenko, Artyom A. Alekseyenko, Yuri B. Schwartz, Aki Minoda, Nicole C. Riddle, Jason Ernst, Peter J. Sabo, Erica Larschan, Andrey A. Gorchakov, Tingting Gu, Daniela Linder-Basso, Annette Plachetka, Gregory Shanower, Michael Y. Tolstorukov, Lovelace J. Luquette, Ruibin Xi, Youngsook L. Jung, Richard W. Park, Eric P. Bishop, Theresa K. Canfield, Richard Sandstrom, Robert E. Thurman, David M. MacAlpine, John A. Stamatoyannopoulos, Manolis Kellis, Sarah C. R. Elgin, Mitzi I. Kuroda, Vincenzo Pirrotta, Gary H. Karpen & Peter J. Park

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized

"

NATURAL GENETIC VARIATION IN SOCIAL ENVIRONMENT CHOICE: CONTEXT-DEPENDENT GENE-ENVIRONMENT CORRELATION IN DROSOPHILA MELANOGASTER

NATURAL GENETIC VARIATION IN SOCIAL ENVIRONMENT CHOICE: CONTEXT-DEPENDENT GENE-ENVIRONMENT CORRELATION IN DROSOPHILA MELANOGASTER: "

ABSTRACT

Gene-environment correlation (‘rGE’) occurs when an individual's genotype determines its choice of environment, generating a correlation between environment and genotype frequency. In particular, social rGE, caused by genetic variation in social environment choice, can critically determine both individual development and the course of social selection. Despite its foundational role in social evolution and developmental psychology theory, natural genetic variation in social environment choice has scarcely been examined empirically. Drosophila melanogaster provides an ideal system for investigating social rGE. Flies live socially in nature and have many opportunities to make social decisions; and natural, heterozygous genotypes may be replicated, enabling comparisons between genotypes across environments. Using this approach, I show that all aspects of social environment choice vary among natural genotypes, demonstrating pervasive social rGE. Surprisingly, genetic variation in group-size preference was density-dependent, indicating that the behavioral and evolutionary consequences of rGE may depend on the context in which social decisions are made. These results provide the first detailed investigation of social rGE, and illustrate that that genetic variation may influence organismal performance by specifying the environment in which traits are expressed.

"

Sequence-dependent cooperative binding of p53 to DNA targets and its relationship to the structural properties of the DNA targets

Sequence-dependent cooperative binding of p53 to DNA targets and its relationship to the structural properties of the DNA targets: "

The prime mechanism by which p53 acts as a tumor suppressor is as a transcription factor regulating the expression of diverse downstream genes. The DNA-binding domain of p53 (p53DBD) interacts with defined DNA sites and is the main target for mutations in human primary tumors. Here, we show that the CWWG motif, found in the center of each consensus p53 half-site, is a key player in p53/DNA interactions. Gel-mobility-shift assays provide a unique opportunity to directly observe the various oligomeric complexes formed between p53DBD and its target sites. We demonstrate that p53DBD binds to p53 consensus sites containing CATG with relatively low cooperativity, as both dimers and tetramers, and with even lower cooperativity to such sites containing spacer sequences. p53DBD binds to sites containing CAAG and CTAG with measurable affinity only when imbedded in two contiguous p53 half-sites and only as tetramers (with very high cooperativity). There are three orders-of-magnitude difference in the cooperativity of interaction between sites differing in their non-contacted step, and further two orders-of-magnitude difference as a function of spacer sequences. By experimentally measuring the global structural properties of these sites, by cyclization kinetics of DNA minicircles, we correlate these differences with the torsional flexibility of the binding sites.

"

Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster

Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster: "Author Summary

Understanding the causes and consequences of natural genetic variation is crucial to the characterization of biological evolution. Moreover, natural genetic variation is comprised of millions of perturbations, which are partially randomized across genotypes such that a small number of individuals can be used to combinatorially analyze a large number of differences, facilitating mechanistic understanding of biological systems. Here we demonstrate a powerful technique to parse genomic variation using artificial selection. By selecting replicate populations of Drosophila flies to become bigger and smaller, and then determining the evolutionary response at the genomic level, we have mapped hundreds of genes that respond to selection on body size. As our approach is powerful and cost-effective compared to existing approaches, we expect it to be a major component of diverse future efforts.

"

Enhancer function: new insights into the regulation of tissue-specific gene expression

Enhancer function: new insights into the regulation of tissue-specific gene expression: "

Enhancer function: new insights into the regulation of tissue-specific gene expression

Nature Reviews Genetics 12, 283 (2011). doi:10.1038/nrg2957

Authors: Chin-Tong Ong & Victor G. Corces

Enhancer function underlies regulatory processes by which cells establish patterns of gene expression. Recent results suggest that many enhancers are specified by particular chromatin marks in pluripotent cells, which may be modified later in development to alter patterns of gene expression and cell differentiation choices.

"

Pattern, Growth, and Control

Pattern, Growth, and Control: "Arthur D. Lander. Systems biology seeks not only to discover the machinery of life but to understand how such machinery is used for control, i.e., for regulation that achieves or maintains a desired, useful end. Th...."

Evolution of Gene Regulatory Networks Controlling Body Plan Development

Evolution of Gene Regulatory Networks Controlling Body Plan Development: "Isabelle S. Peter, Eric H. Davidson. Evolutionary change in animal morphology results from alteration of the functional organization of the gene regulatory networks (GRNs) that control development of the body plan. A major mechanism ...."

Informing Biological Design by Integration of Systems and Synthetic Biology

Informing Biological Design by Integration of Systems and Synthetic Biology: "Christina D. Smolke, Pamela A. Silver. Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the d...."

Boosting Signal-to-Noise in Complex Biology: Prior Knowledge Is Power

Boosting Signal-to-Noise in Complex Biology: Prior Knowledge Is Power: "Trey Ideker, Janusz Dutkowski, Leroy Hood. A major difficulty in the analysis of complex biological systems is dealing with the low signal-to-noise inherent to nearly all large biological datasets. We discuss powerful bioinformatic concept...."

Impulse Control: Temporal Dynamics in Gene Transcription

Impulse Control: Temporal Dynamics in Gene Transcription: "Nir Yosef, Aviv Regev. Regulatory circuits controlling gene expression constantly rewire to adapt to environmental stimuli, differentiation cues, and disease. We review our current understanding of the temporal dynamics...."

Pbx homeodomain proteins: TALEnted regulators of limb patterning and outgrowth

Pbx homeodomain proteins: TALEnted regulators of limb patterning and outgrowth: "

Abstract

Limb development has long provided an excellent model for understanding the genetic principles driving embryogenesis. Studies utilizing chick and mouse have led to new insights into limb patterning and morphogenesis. Recent research has centered on the regulatory networks underlying limb development. Here, we discuss the hierarchical, overlapping, and iterative roles of Pbx family members in appendicular development that have emerged from genetic analyses in the mouse. Pbx genes are essential in determining limb bud positioning, early bud formation, limb axes establishment and coordination, and patterning and morphogenesis of most elements of the limb and girdle. Pbx proteins directly regulate critical effectors of limb and girdle development, including morphogen-encoding genes like Shh in limb posterior mesoderm, and transcription factor-encoding genes like Alx1 in pre-scapular domains. Interestingly, at least in limb buds, Pbx appear to act not only as Hox cofactors, but also in the upstream control of 5′ HoxA/D gene expression. Developmental Dynamics, 2011. © 2011 Wiley-Liss, Inc.

"

What is parallelism?

What is parallelism?: "

SUMMARY
Although parallel and convergent evolution are discussed extensively in technical articles and textbooks, their meaning can be overlapping, imprecise, and contradictory. The meaning of parallel evolution in much of the evolutionary literature grapples with two separate hypotheses in relation to phenotype and genotype, but often these two hypotheses have been inferred from only one hypothesis, and a number of subsidiary but problematic criteria, in relation to the phenotype. However, examples of parallel evolution of genetic traits that underpin or are at least associated with convergent phenotypes are now emerging. Four criteria for distinguishing parallelism from convergence are reviewed. All are found to be incompatible with any single proposition of homoplasy. Therefore, all homoplasy is equivalent to a broad view of convergence. Based on this concept, all phenotypic homoplasy can be described as convergence and all genotypic homoplasy as parallelism, which can be viewed as the equivalent concept of convergence for molecular data. Parallel changes of molecular traits may or may not be associated with convergent phenotypes but if so describe homoplasy at two biological levels—genotype and phenotype. Parallelism is not an alternative to convergence, but rather it entails homoplastic genetics that can be associated with and potentially explain, at the molecular level, how convergent phenotypes evolve.

"

The evolution of oocyte patterning in insects: multiple cell-signaling pathways are active during honeybee oogenesis and are likely to play a role in axis patterning

The evolution of oocyte patterning in insects: multiple cell-signaling pathways are active during honeybee oogenesis and are likely to play a role in axis patterning: "

SUMMARY
In Drosophila it is well established that signaling between the germline and surrounding follicle cells establishes the axes of the future embryo and is required for patterning of the eggshell. However, little is known about how this is achieved in other insects. Genome sequencing studies imply that maternal axis determination may be rapidly evolving, as a number of Drosophila maternal patterning genes are absent from the genomes of other insects. We have examined the distribution and function of six developmental signaling pathways present, and active, in honeybee ovarioles. We have confirmed an evolutionarily conserved role for transforming growth factor-α–epidermal growth factor receptor signaling in dorsal—ventral (DV) patterning. We also found evidence for the involvement of Dpp/Mad and JNK–MAPK pathways in DV patterning, unlike Drosophila. Several of these pathways are also active in the germarium, implicating them in germ and somatic stem cell maintenance and proliferation, similar to their activities in Drosophila ovaries.

"

Improving animal phylogenies with genomic data

Improving animal phylogenies with genomic data: "Maximilian J. Telford, Richard R. Copley. Since the first animal genomes were completely sequenced ten years ago, evolutionary biologists have attempted to use the encoded information to reconstruct different aspects of the earliest stage...."

Mechanism of Chromosomal Boundary Action: Roadblock, Sink, or Loop? [Gene expression]

Mechanism of Chromosomal Boundary Action: Roadblock, Sink, or Loop? [Gene expression]: "

Boundary elements or insulators subdivide eukaryotic chromosomes into a series of structurally and functionally autonomous domains. They ensure that the action of enhancers and silencers is restricted to the domain in which these regulatory elements reside. Three models, the roadblock, sink/decoy, and topological loop, have been proposed to explain the insulating activity of boundary elements. Strong predictions about how boundaries will function in different experimental contexts can be drawn from these models. In the studies reported here, we have designed assays that test these predictions. The results of our assays are inconsistent with the expectations of the roadblock and sink models. Instead, they support the topological loop model.

"

Evolution of a malaria resistance gene in wild primates

Nature 460, 388-391 (16 July 2009) | doi:10.1038/nature08149; Received 4 March 2009; Accepted 15 May 2009; Published online 24 June 2009
The ecology, behaviour and genetics of our closest living relatives, the nonhuman primates, should help us to understand the evolution of our own lineage. Although a large amount of data has been amassed on primate ecology and behaviour, much less is known about the functional and evolutionary genetic aspects of primate biology, especially in wild primates. As a result, even in well-studied populations in which nongenetic factors that influence adaptively important characteristics have been identified, we have almost no understanding of the underlying genetic basis for such traits. Here, we report on the functional consequences of genetic variation at the malaria-related FY (DARC) gene in a well-studied population of yellow baboons (Papio cynocephalus) living in Amboseli National Park in Kenya. FY codes for a chemokine receptor normally expressed on the erythrocyte surface that is the known entry point for the malarial parasite Plasmodium vivax ^{1, 2, 3}. We identified variation in the cis-regulatory region of the baboon FY gene that was associated with phenotypic variation in susceptibility to Hepatocystis, a malaria-like pathogen that is common in baboons^{4, 5}. Genetic variation in this region also influenced gene expression in vivo in wild individuals, a result we confirmed using in vitro reporter gene assays. The patterns of genetic variation in and around this locus were also suggestive of non-neutral evolution, raising the possibility that the evolution of the FY cis-regulatory region in baboons has exhibited both mechanistic and selective parallels with the homologous region in humans^{6, 7, 8}. Together, our results represent the first reported association and functional characterization linking genetic variation and a complex trait in a natural population of nonhuman primates.

Evolution of a tissue-specific splicing network [Research Papers]

Evolution of a tissue-specific splicing network [Research Papers]: "

Alternative splicing of precursor mRNA (pre-mRNA) is a strategy employed by most eukaryotes to increase transcript and proteomic diversity. Many metazoan splicing factors are members of multigene families, with each member having different functions. How these highly related proteins evolve unique properties has been unclear. Here we characterize the evolution and function of a new Drosophila splicing factor, termed LS2 (Large Subunit 2), that arose from a gene duplication event of dU2AF⁵⁰, the large subunit of the highly conserved heterodimeric general splicing factor U2AF (U2-associated factor). The quickly evolving LS2 gene has diverged from the splicing-promoting, ubiquitously expressed dU2AF⁵⁰ such that it binds a markedly different RNA sequence, acts as a splicing repressor, and is preferentially expressed in testes. Target transcripts of LS2 are also enriched for performing testes-related functions. We therefore propose a path for the evolution of a new splicing factor in Drosophila that regulates specific pre-mRNAs and contributes to transcript diversity in a tissue-specific manner.

"

Subnuclear segregation of genes and core promoter factors in myogenesis [Research Papers]

Subnuclear segregation of genes and core promoter factors in myogenesis [Research Papers]: "

Recent findings implicate alternate core promoter recognition complexes in regulating cellular differentiation. Here we report a spatial segregation of the alternative core factor TAF3, but not canonical TFIID subunits, away from the nuclear periphery, where the key myogenic gene MyoD is preferentially localized in myoblasts. This segregation is correlated with the differential occupancy of TAF3 versus TFIID at the MyoD promoter. Loss of this segregation by modulating either the intranuclear location of the MyoD gene or TAF3 protein leads to altered TAF3 occupancy at the MyoD promoter. Intriguingly, in differentiated myotubes, the MyoD gene is repositioned to the nuclear interior, where TAF3 resides. The specific high-affinity recognition of H3K4Me3 by the TAF3 PHD (plant homeodomain) finger appears to be required for the sequestration of TAF3 to the nuclear interior. We suggest that intranuclear sequestration of core transcription components and their target genes provides an additional mechanism for promoter selectivity during differentiation.

"

Sexual and postmating reproductive isolation between allopatric Drosophila montana populations suggest speciation potential

Sexual and postmating reproductive isolation between allopatric Drosophila montana populations suggest speciation potential: "Background:
Widely distributed species with populations adapted to different environmental conditions can provide valuable opportunities for tracing the onset of reproductive incompatibilities and their role in the speciation process. Drosophila montana, a D. virilis group species found in high latitude boreal forests in Nearctic and Palearctic regions around the globe, could be an excellent model system for studying the early stages of speciation, as a wealth of information concerning this species' ecology, mating system, life history, genetics and phylogeography is available. However, reproductive barriers between populations have hereto not been investigated.
Results:
We report both pre- and postmating barriers to reproduction between flies from European (Finnish) and North American (Canadian) populations of Drosophila montana. Using a series of mate-choice designs, we show that flies from these two populations mate assortatively (i.e., exhibit significant sexual isolation) while emphasizing the importance of experimental design in these kinds of studies. We also assessed potential postmating isolation by quantifying egg and progeny production in intra- and interpopulation crosses and show a significant one-way reduction in progeny production, affecting both male and female offspring equally.
Conclusion:
We provide evidence that allopatric D. montana populations exhibit reproductive isolation and we discuss the potential mechanisms involved. Our data emphasize the importance of experimental design in studies on premating isolation between recently diverged taxa and suggest that postmating barriers may be due to postcopulatory-prezygotic mechanisms. D. montana populations seem to be evolving multiple barriers to gene flow in allopatry and our study lays the groundwork for future investigations of the genetic and phenotypic mechanisms underlying these barriers."

CONVERGENCE, ADAPTATION AND CONSTRAINT

CONVERGENCE, ADAPTATION AND CONSTRAINT: "

ABSTRACT

Convergent evolution of similar phenotypic features in similar environmental contexts has long been taken as evidence of adaptation. Nonetheless, recent conceptual and empirical developments in many fields have led to a proliferation of ideas about the relationship between convergence and adaptation. Despite criticism from some systematically-minded biologists, I reaffirm that convergence in taxa occupying similar selective environments often is the result of natural selection. However, convergent evolution of a trait in a particular environment can occur for reasons other than selection on that trait in that environment, and species can respond to similar selective pressures by evolving non-convergent adaptations. For these reasons, studies of convergence should be coupled with other methods—such as direct measurements of selection or investigations of the functional correlates of trait evolution—to test hypotheses of adaptation. The independent acquisition of similar phenotypes by the same genetic or developmental pathway has been suggested as evidence of constraints on adaptation, a view widely repeated as genomic studies have documented phenotypic convergenc resulting from change in the same genes, sometimes even by the same mutation. Contrary to some claims, convergence by changes in the same genes is not necessarily evidence of constraint, but rather suggests hypotheses that can test the relative roles of constraint and selection in directing phenotypic evolution.

"

Human-specific loss of regulatory DNA and the evolution of human-specific traits

Human-specific loss of regulatory DNA and the evolution of human-specific traits: "

Human-specific loss of regulatory DNA and the evolution of human-specific traits

Nature 471, 7337 (2011). doi:10.1038/nature09774

Authors: Cory Y. McLean, Philip L. Reno, Alex A. Pollen, Abraham I. Bassan, Terence D. Capellini, Catherine Guenther, Vahan B. Indjeian, Xinhong Lim, Douglas B. Menke, Bruce T. Schaar, Aaron M. Wenger, Gill Bejerano & David M. Kingsley

Humans differ from other animals in many aspects of anatomy, physiology, and behaviour; however, the genotypic basis of most human-specific traits remains unknown. Recent whole-genome comparisons have made it possible to identify genes with elevated rates of amino acid change or divergent expression in humans, and non-coding sequences with accelerated base pair changes. Regulatory alterations may be particularly likely to produce phenotypic effects while preserving viability, and are known to underlie interesting evolutionary differences in other species. Here we identify molecular events particularly likely to produce significant regulatory changes in humans: complete deletion of sequences otherwise highly conserved between chimpanzees and other mammals. We confirm 510 such deletions in humans, which fall almost exclusively in non-coding regions and are enriched near genes involved in steroid hormone signalling and neural function. One deletion removes a sensory vibrissae and penile spine enhancer from the human androgen receptor (AR) gene, a molecular change correlated with anatomical loss of androgen-dependent sensory vibrissae and penile spines in the human lineage. Another deletion removes a forebrain subventricular zone enhancer near the tumour suppressor gene growth arrest and DNA-damage-inducible, gamma (GADD45G), a loss correlated with expansion of specific brain regions in humans. Deletions of tissue-specific enhancers may thus accompany both loss and gain traits in the human lineage, and provide specific examples of the kinds of regulatory alterations and inactivation events long proposed to have an important role in human evolutionary divergence.

"

Core promoter recognition complex changes accompany liver development [Biochemistry]

Core promoter recognition complex changes accompany liver development [Biochemistry]: "Recent studies of several key developmental transitions have brought into question the long held view of the basal transcriptional apparatus as ubiquitous and invariant. In an effort to better understand the role of core promoter recognition and coactivator complex switching in cellular differentiation, we have examined changes in transcription factor IID (TFIID) and cofactor required for Sp1 activation/Mediator during mouse liver development. Here we show that the differentiation of fetal liver progenitors to adult hepatocytes involves a wholesale depletion of canonical cofactor required for Sp1 activation/Mediator and TFIID complexes at both the RNA and protein level, and that this alteration likely involves silencing of transcription factor promoters as well as protein degradation. It will be intriguing for future studies to determine if a novel and as yet unknown core promoter recognition complex takes the place of TFIID in adult hepatocytes and to uncover the mechanisms that down-regulate TFIID during this critical developmental transition."

Alcoholic Beverages Induce Superconductivity

Alcoholic Beverages Induce Superconductivity: "

Wine can help keep conversation flowing at a dinner party. And now it looks like that wine may aid in materials science as well. Japanese researchers discovered that hot alcoholic beverages induce superconductivity in iron-based compounds.

[More]"

FITNESS RECOVERY AND COMPENSATORY EVOLUTION IN NATURAL MUTANT LINES OF C. ELEGANS

FITNESS RECOVERY AND COMPENSATORY EVOLUTION IN NATURAL MUTANT LINES OF C. ELEGANS: "

ABSTRACT

Deleterious mutation accumulation plays a central role in evolutionary genetics, conservation biology, human health, and evolutionary medicine (e.g., methods of viral attenuation for live vaccines). It is therefore important to understand whether and how quickly populations with accumulated deleterious mutational loads can recover fitness through adaptive evolution. We used laboratory experimental evolution with four long-term mutation-accumulation (MA) lines of Caenorhabditis elegans nematodes to study the dynamics of such fitness evolution. We previously showed that when homozygous mutant populations are evolved in large population sizes, they can rapidly achieve wild type fitness through the accumulation of new beneficial or compensatory epistatic mutations. Here we expand this approach to demonstrate that when replicate lineages are initiated from the same mutant genotype, phenotypic evolution is only sometimes repeatable. MA genotypes that recovered ancestral fitness in the previous experiment did not always do so here. Further, the pattern of adaptive evolution in independently evolved replicates was contingent upon the MA genotype and varied among fitness-related traits. Our findings suggest that new beneficial mutations can drive rapid fitness evolution, but that the adaptive process is rendered somewhat unpredictable by its susceptibility to chance events and sensitivity to the evolutionary history of the starting population.

"

A Bow-Tie Genetic Architecture for Morphogenesis Suggested by a Genome-Wide RNAi Screen in Caenorhabditis elegans

A Bow-Tie Genetic Architecture for Morphogenesis Suggested by a Genome-Wide RNAi Screen in Caenorhabditis elegans: "Author Summary

Morphogenesis is a process in which cells change their shape and position to give rise to mature structures. Elucidation of the molecular basis of morphogenesis and its regulation would be a major step towards understanding organ formation and functionality. We focus on a powerful model for morphogenesis, the four-celled tail tip of the C. elegans male, which undergoes morphogenesis during the last larval stage. To comprehensively determine the components that regulate and execute male tail tip morphogenesis, we performed a genome-wide RNAi screen. We identified 212 genes that encode proteins with roles in fundamental processes like endocytosis, vesicular trafficking, cell–cell communication, and cytoskeletal organization. We determined the interactions among several of these genes to reconstruct a first draft of the genetic network underlying tail tip morphogenesis. The structure of this network is consistent with the 'bow-tie architecture' that has been proposed to be universal and confers evolvability and robustness to biological systems. Bow-tie networks have a conserved core which is linked to numerous input and output components. Many components of the network underlying tail tip morphogenesis in C. elegans are conserved all the way to humans. Thus, understanding tail tip morphogenesis will inform us about morphogenesis in other organisms.

"

[Research Article] Dynamics of Dpp Signaling and Proliferation Control

[Research Article] Dynamics of Dpp Signaling and Proliferation Control: "Mitosis starts when morphogen signaling levels have increased by half since the beginning of the cell cycle.

Authors: O. Wartlick, P. Mumcu, A. Kicheva, T. Bittig, C. Seum, F. Jülicher, M. González-Gaitán"

Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression

Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression: "Author Summary

Stochastic chemical kinetics provides a framework for modeling gene regulation at the single-cell level. Using this framework, we systematically investigate the effect of promoter architecture, that is, the number, quality and position of transcription factor binding sites, on cell-to-cell variability in transcription levels. We compare architectures resulting in transcriptional activation with those resulting in transcriptional repression. We start from simple activation and repression motifs with a single operator sequence, and explore the parameter regime for which the cell-to-cell variability is maximal. Using the same formalism, we then turn to more complicated architectures with more than one operator. We examine the effect of independent and cooperative binding, as well as the role of DNA mechanics for those architectures where DNA looping is relevant. We examine the interplay between operator strength and operator number, and we make specific predictions for single-cell mRNA-counting experiments with well characterized promoters. This theoretical approach makes it possible to find the statistical response of a population of cells to perturbations in the architecture of the promoter; it can be used to quantitatively test physical models of gene regulation in vivo, and as the basis of a more systematic approach to designing new promoter architectures.

"

The Formation of the Bicoid Morphogen Gradient Requires Protein Movement from Anteriorly Localized mRNA

The Formation of the Bicoid Morphogen Gradient Requires Protein Movement from Anteriorly Localized mRNA: "

New quantitative data show that the Bicoid morphogen gradient is generated from a dynamic localized source and that protein gradient formation requires protein movement along the anterior-posterior axis.

"

PoPoolation DB: a user-friendly web-based database for the retrieval of natural polymorphisms in Drosophila

PoPoolation DB: a user-friendly web-based database for the retrieval of natural polymorphisms in Drosophila: "Background:
The enormous potential of natural variation for the functional characterization of genes has been neglected for a long time. Only since recently, functional geneticists are starting to account for natural variation in their analyses. With the new sequencing technologies it has become feasible to collect sequence information for multiple individuals on a genomic scale. In particular sequencing pooled DNA samples has been shown to provide a cost-effective approach for characterizing variation in natural populations. While a range of software tools have been developed for mapping these reads onto a reference genome and extracting SNPs, linking this information to population genetic estimators and functional information still poses a major challenge to many researchers.
Results:
We developed PoPoolation DB a user-friendly integrated database. Popoolation DB links variation in natural populations with functional information, allowing a wide range of researchers to take advantage of population genetic data. PoPoolation DB provides the user with population genetic parameters (Watterson's theta or Tajima's pi), Tajima's D, SNPs, allele frequencies and indels in a region of interest. The database could be queried by gene name, chromosomal position, or a user-provided query sequence or GTF file. We anticipate that PoPoolation DB will be a highly versatile tool for functional geneticists as well as evolutionary biologists.
Conclusions:
PoPoolation DB, available at http://www.popoolation.at/pgt, provides an integrated platform for researchers to investigate natural polymorphism and associated functional annotations from UCSC and Flybase genome browsers, population genetic estimators and RNA-seq information."

X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila

X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila: "

X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila

Nature 471, 7336 (2011). doi:10.1038/nature09757

Authors: Erica Larschan, Eric P. Bishop, Peter V. Kharchenko, Leighton J. Core, John T. Lis, Peter J. Park & Mitzi I. Kuroda

The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3′ ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

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Somatic coding mutations in human induced pluripotent stem cells

Somatic coding mutations in human induced pluripotent stem cells: "

Somatic coding mutations in human induced pluripotent stem cells

Nature 471, 7336 (2011). doi:10.1038/nature09805

Authors: Athurva Gore, Zhe Li, Ho-Lim Fung, Jessica E. Young, Suneet Agarwal, Jessica Antosiewicz-Bourget, Isabel Canto, Alessandra Giorgetti, Mason A. Israel, Evangelos Kiskinis, Je-Hyuk Lee, Yuin-Han Loh, Philip D. Manos, Nuria Montserrat, Athanasia D. Panopoulos, Sergio Ruiz, Melissa L. Wilbert, Junying Yu, Ewen F. Kirkness, Juan Carlos Izpisua Belmonte, Derrick J. Rossi, James A. Thomson, Kevin Eggan, George Q. Daley, Lawrence S. B. Goldstein & Kun Zhang

Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced

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High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells [METHOD]

High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells [METHOD]: "

Regulation of gene transcription in diverse cell types is determined largely by varied sets of cis-elements where transcription factors bind. Here we demonstrate that data from a single high-throughput DNase I hypersensitivity assay can delineate hundreds of thousands of base-pair resolution in vivo footprints in human cells that precisely mark individual transcription factor–DNA interactions. These annotations provide a unique resource for the investigation of cis-regulatory elements. We find that footprints for specific transcription factors correlate with ChIP-seq enrichment and can accurately identify functional versus nonfunctional transcription factor motifs. We also find that footprints reveal a unique evolutionary conservation pattern that differentiates functional footprinted bases from surrounding DNA. Finally, detailed analysis of CTCF footprints suggests multiple modes of binding and a novel DNA binding motif upstream of the primary binding site.

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Nucleotide composition-linked divergence of vertebrate core promoter architecture [RESEARCH]

Nucleotide composition-linked divergence of vertebrate core promoter architecture [RESEARCH]: "

Transcription initiation involves the recruitment of basal transcription factors to the core promoter. A variety of core promoter elements exists; however for most of these motifs, the distribution across species is unknown. Here we report on the comparison of human and amphibian promoter sequences. We have used oligo-capping in combination with deep sequencing to determine transcription start sites in Xenopus tropicalis. To systematically predict regulatory elements, we have developed a de novo motif finding pipeline using an ensemble of computational tools. A comprehensive comparison of human and amphibian promoter sequences revealed both similarities and differences in core promoter architecture. Some of the differences stem from a highly divergent nucleotide composition of Xenopus and human promoters. Whereas the distribution of some core promoter motifs is conserved independently of species-specific nucleotide bias, the frequency of another class of motifs correlates with the single nucleotide frequencies. This class includes the well-known TATA box and SP1 motifs, which are more abundant in Xenopus and human promoters, respectively. While these motifs are enriched above the local nucleotide background in both organisms, their frequency varies in step with this background. These differences are likely adaptive as these motifs can recruit TFIID to either CpG island or sharply initiating promoters. Our results highlight both the conserved and diverged aspects of vertebrate transcription, most notably showing co-opted motif usage to recruit the transcriptional machinery to promoters with diverging nucleotide composition. This shows how sweeping changes in nucleotide composition are compatible with highly conserved mechanisms of transcription initiation.

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