Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning

Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning: "Nadya Kondrashov, Aya Pusic, Craig R. Stumpf, Kunihiko Shimizu, Andrew C. Hsieh, Shifeng Xue, Junko Ishijima, Toshihiko Shiroishi, Maria Barna. Historically, the ribosome has been viewed as a complex ribozyme with constitutive rather than regulatory capacity in mRNA translation. Here we identify mutations of the Ribosomal Protein L38 (...."

An Epigenetic Signature for Monoallelic Olfactory Receptor Expression

An Epigenetic Signature for Monoallelic Olfactory Receptor Expression: "Angeliki Magklara, Angela Yen, Bradley M. Colquitt, E. Josephine Clowney, William Allen, Eirene Markenscoff-Papadimitriou, Zoe A. Evans, Pouya Kheradpour, George Mountoufaris, Catriona Carey, Gilad Barnea, Manolis Kellis, Stavros Lomvardas. Constitutive heterochromatin is traditionally viewed as the static form of heterochromatin that silences pericentromeric and telomeric repeats in a cell cycle- and differentiation-independent mann...."

High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species

High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species: "

High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species

Nature Genetics 43, 414 (2011).
doi:10.1038/ng.808

Authors: Qiye He, Anaïs F Bardet, Brianne Patton, Jennifer Purvis, Jeff Johnston, Ariel Paulson, Madelaine Gogol, Alexander Stark & Julia Zeitlinger

"

Growth and development

Growth and development: "

Growth and development

Nature Communications 2, 295 (2011). doi:10.1038/ncomms1322

With a year of publications under its belt, Nature Communications has established itself as an accommodating venue for the natural sciences.

"

Formation of stress-specific p53 binding patterns is influenced by chromatin but not by modulation of p53 binding affinity to response elements

Formation of stress-specific p53 binding patterns is influenced by chromatin but not by modulation of p53 binding affinity to response elements: "

The p53 protein is crucial for adapting programs of gene expression in response to stress. Recently, we revealed that this occurs partly through the formation of stress-specific p53 binding patterns. However, the mechanisms that generate these binding patterns remain largely unknown. It is not established whether the selective binding of p53 is achieved through modulation of its binding affinity to certain response elements (REs) or via a chromatin-dependent mechanism. To shed light on this issue, we used a microsphere assay for protein–DNA binding to measure p53 binding patterns on naked DNA. In parallel, we measured p53 binding patterns within chromatin using chromatin immunoprecipitation and DNase I coupled to ligation-mediated polymerase chain reaction footprinting. Through this experimental approach, we revealed that UVB and Nutlin-3 doses, which lead to different cellular outcomes, induce similar p53 binding patterns on naked DNA. Conversely, the same treatments lead to stress-specific p53 binding patterns on chromatin. We show further that altering chromatin remodeling using an histone acetyltransferase inhibitor reduces p53 binding to REs. Altogether, our results reveal that the formation of p53 binding patterns is not due to the modulation of sequence-specific p53 binding affinity. Rather, we propose that chromatin and chromatin remodeling are required in this process.
"

Selective interactions of boundaries with upstream region of Abd-B promoter in Drosophila bithorax complex and role of dCTCF in this process

Selective interactions of boundaries with upstream region of Abd-B promoter in Drosophila bithorax complex and role of dCTCF in this process: "

Expression of the genes Ubx, abd-A, and Abd-B of the bithorax complex depends on its cis-regulatory region, which is divided into discrete functional domains (iab). Boundary/insulator elements, named Mcp, Fab-6, Fab-7 and Fab-8 (PTS/F8), have been identified at the borders of the iab domains. Recently, binding sites for a Drosophila homolog of the vertebrate insulator protein CTCF have been identified in Mcp, Fab-6 and Fab-8 and also in several regions that correspond to predicted boundaries, Fab-3 and Fab-4 in particular. Taking into account the inability of the yeast GAL4 activator to stimulate the white promoter when the activator and the promoter are separated by a 5-kb yellow gene, we have tested functional interactions between the boundaries. The results show that all dCTCF-containing boundaries interact with each other. However, inactivation of dCTCF binding sites in Mcp, Fab-6 and PTS/F8 only partially reduces their ability to interact, suggesting the presence of additional protein(s) supporting distant interactions between the boundaries. Interestingly, only Fab-6, Fab-7 (which contains no dCTCF binding sites) and PTS/F8 interact with the upstream region of the Abd-B promoter. Thus, the boundaries might be involved in supporting the specific interactions between iab enhancers and promoters of the bithorax complex.

"

Genome-wide analysis reveals novel molecular features of mouse recombination hotspots

Genome-wide analysis reveals novel molecular features of mouse recombination hotspots: "

Genome-wide analysis reveals novel molecular features of mouse recombination hotspots

Nature 472, 7343 (2011). doi:10.1038/nature09869

Authors: Fatima Smagulova, Ivan V. Gregoretti, Kevin Brick, Pavel Khil, R. Daniel Camerini-Otero & Galina V. Petukhova

Meiotic recombination predominantly occurs at discrete genomic loci called recombination hotspots, but the features defining these areas are still largely unknown (reviewed in refs 1–5). To allow a comprehensive analysis of hotspot-associated DNA and chromatin characteristics, we developed a direct molecular approach for mapping meiotic DNA double-strand breaks that initiate recombination. Here we present the genome-wide distribution of recombination initiation sites in the mouse genome. Hotspot centres are mapped with approximately 200-nucleotide precision, which allows analysis of the fine structural details of the preferred recombination sites. We determine that hotspots share a centrally distributed consensus motif, possess a nucleotide skew that changes polarity at the centres of hotspots and have an intrinsic preference to be occupied by a nucleosome. Furthermore, we find that the vast majority of recombination initiation sites in mouse males are associated with testis-specific trimethylation of lysine 4 on histone H3 that is distinct from histone H3 lysine 4 trimethylation marks associated with transcription. The recombination map presented here has been derived from a homogeneous mouse population with a defined genetic background and therefore lends itself to extensive future experimental exploration. We note that the mapping technique developed here does not depend on the availability of genetic markers and hence can be easily adapted to other species with complex genomes. Our findings uncover several fundamental features of mammalian recombination hotspots and underline the power of the new recombination map for future studies of genetic recombination, genome stability and evolution.

"

Determinants of Synonymous and Nonsynonymous Variability in Three Species of Drosophila

Determinants of Synonymous and Nonsynonymous Variability in Three Species of Drosophila: "

We estimated the intensity of selection on preferred codons in Drosophila pseudoobscura and D. miranda at X-linked and autosomal loci, using a published data set on sequence variability at 67 loci, by means of an improved method that takes account of demographic effects. We found evidence for stronger selection at X-linked loci, consistent with their higher levels of codon usage bias. The estimates of the strength of selection and mutational bias in favor of unpreferred codons were similar to those found in other species, after taking into account the fact that D. pseudoobscura showed evidence for a recent expansion in population size. We examined correlates of synonymous and nonsynonymous diversity in these species and found no evidence for effects of recurrent selective sweeps on nonsynonymous mutations, which is probably because this set of genes have much higher than average levels of selective constraints. There was evidence for correlated effects of levels of selective constraints on protein sequences and on codon usage, as expected under models of selection for translational accuracy. Our analysis of a published data set on D. melanogaster provided evidence for the effects of selective sweeps of nonsynonymous mutations on linked synonymous diversity, but only in the subset of loci that experienced the highest rates of nonsynonymous substitutions (about one-quarter of the total) and not at more slowly evolving loci. Our correlational analysis of this data set suggested that both selective constraints on protein sequences and recurrent selective sweeps affect the overall level of codon usage.

"

Population Genomics of Transposable Elements in Drosophila melanogaster

Population Genomics of Transposable Elements in Drosophila melanogaster: "

Transposable elements (TEs) are the primary contributors to the genome bulk in many organisms and are major players in genome evolution. A clear and thorough understanding of the population dynamics of TEs is therefore essential for full comprehension of the eukaryotic genome evolution and function. Although TEs in Drosophila melanogaster have received much attention, population dynamics of most TE families in this species remains entirely unexplored. It is not clear whether the same population processes can account for the population behaviors of all TEs in Drosophila or whether, as has been suggested previously, different orders behave according to very different rules. In this work, we analyzed population frequencies for a large number of individual TEs (755 TEs) in five North American and one sub-Saharan African D. melanogaster populations (75 strains in total). These TEs have been annotated in the reference D. melanogaster euchromatic genome and have been sampled from all three major orders (non-LTR, LTR, and TIR) and from all families with more than 20 TE copies (55 families in total). We find strong evidence that TEs in Drosophila across all orders and families are subject to purifying selection at the level of ectopic recombination. We showed that strength of this selection varies predictably with recombination rate, length of individual TEs, and copy number and length of other TEs in the same family. Importantly, these rules do not appear to vary across orders. Finally, we built a statistical model that considered only individual TE-level (such as the TE length) and family-level properties (such as the copy number) and were able to explain more than 40% of the variation in TE frequencies in D. melanogaster.

"

Late Carboniferous paleoichnology reveals the oldest full-body impression of a flying insect [Geology]

Late Carboniferous paleoichnology reveals the oldest full-body impression of a flying insect [Geology]: "Insects were the first animals to evolve powered flight and did so perhaps 90 million years before the first flight among vertebrates. However, the earliest fossil record of flying insect lineages (Pterygota) is poor, with scant indirect evidence from the Devonian and a nearly complete dearth of material from the Early Carboniferous. By the Late Carboniferous a diversity of flying lineages is known, mostly from isolated wings but without true insights into the paleoethology of these taxa. Here, we report evidence of a full-body impression of a flying insect from the Late Carboniferous Wamsutta Formation of Massachusetts, representing the oldest trace fossil of Pterygota. Through ethological and morphological analysis, the trace fossil provides evidence that its maker was a flying insect and probably was representative of a stem-group lineage of mayflies. The nature of this current full-body impression somewhat blurs distinctions between the systematics of traces and trace makers, thus adding to the debate surrounding ichnotaxonomy for traces with well-associated trace makers."

Impact of gene expression noise on organismal fitness and the efficacy of natural selection [Evolution]

Impact of gene expression noise on organismal fitness and the efficacy of natural selection [Evolution]: "Many cellular processes are subject to substantial stochastic variation, because they depend on interactions among a small number of molecules. For example, the transcriptional initiation of a gene in a haploid cell relies on the binding of the transcriptional machinery to a single DNA molecule. The stochastic nature of this and other molecular interactions results in a large variation in the expression of the same gene by different isogenic cells under the same environment (1–3). How and to what extent such molecule-level stochasticity affects the wellbeing of organisms and their evolution is not well-understood. Recent experimental characterization of gene expression..."

Mapping Gene Expression in Two Xenopus Species: Evolutionary Constraints and Developmental Flexibility

Mapping Gene Expression in Two Xenopus Species: Evolutionary Constraints and Developmental Flexibility: "Itai Yanai, Leonid Peshkin, Paul Jorgensen, Marc W. Kirschner. Changes in gene expression are thought to be important for morphological evolution, though little is known about the nature or magnitude of the differences. Here, we examine Xenopus laevis ...."

Establishment of Medial Fates along the Proximodistal Axis of the Drosophila Leg through Direct Activation of dachshund by Distalless

Establishment of Medial Fates along the Proximodistal Axis of the Drosophila Leg through Direct Activation of dachshund by Distalless: "Matt W. Giorgianni, Richard S. Mann. The proximodistal (PD) axis of the Drosophila leg is thought to be established by the combined gradients of two secreted morphogens, Wingless (Wg) and Decapentaplegic (Dpp). According to th...."

LEAFY Target Genes Reveal Floral Regulatory Logic, cis Motifs, and a Link to Biotic Stimulus Response

LEAFY Target Genes Reveal Floral Regulatory Logic, cis Motifs, and a Link to Biotic Stimulus Response: "Cara M. Winter, Ryan S. Austin, Servane Blanvillain-Baufumé, Maxwell A. Reback, Marie Monniaux, Miin-Feng Wu, Yi Sang, Ayako Yamaguchi, Nobutoshi Yamaguchi, Jane E. Parker, Francois Parcy, Shane T. Jensen, Hongzhe Li, Doris Wagner. The transition from vegetative growth to flower formation is critical for the survival of flowering plants. The plant-specific transcription factor LEAFY (LFY) has central, evolutionarily conserve...."

ADAPTIVE CHROMOSOMAL DIVERGENCE DRIVEN BY MIXED GEOGRAPHIC MODE OF EVOLUTION

ADAPTIVE CHROMOSOMAL DIVERGENCE DRIVEN BY MIXED GEOGRAPHIC MODE OF EVOLUTION: "

ABSTRACT

Chromosomal inversions are ubiquitous in nature and of great significance for understanding adaptation and speciation. Inversions were the first markers used to investigate the genetic structure of natural populations, leading to the concept of coadapted gene complexes and theories concerning founder effects and genetic drift in small populations. However, we still lack elements of a general theory accounting for the origins and distribution of inversions in nature. Here, we use computer simulations to show that a ‘mixed geographic mode’ of evolution involving allopatric separation of populations followed by secondary contact and gene flow generates chromosomal divergence by natural selection under wider conditions than previous hypotheses. This occurs because inversions arising in allopatry contain a full complement of locally-adapted genes. Once gene flow ensues, reduced recombination within inversions keeps these favorable genotypic combinations intact, resulting in inverted genomic regions being favored over collinear regions. This process allows inversions to establish to high frequencies. Our model can account for several classic patterns in the geographic distribution of inversions and highlights how selection on standing genetic variation allows rapid chromosomal evolution without the waiting time for new mutations. As inversion differences often separate closely related taxa, mixed modes of divergence could be common."

After Dobzhansky & Sturtevant (1938)

Genome structural variation discovery and genotyping

Genome structural variation discovery and genotyping: "

Genome structural variation discovery and genotyping

Nature Reviews Genetics 12, 363 (2011).
doi:10.1038/nrg2958

Authors: Can Alkan, Bradley P. Coe & Evan E. Eichler

Comparisons of human genomes show that more base pairs are altered as a result of structural variation — including copy number variation — than as a result of point mutations. Here we review advances and challenges in the discovery and genotyping of structural variation. The

"

Thermal Robustness of Signaling in Bacterial Chemotaxis

Thermal Robustness of Signaling in Bacterial Chemotaxis: "Olga Oleksiuk, Vladimir Jakovljevic, Nikita Vladimirov, Ricardo Carvalho, Eli Paster, William S. Ryu, Yigal Meir, Ned S. Wingreen, Markus Kollmann, Victor Sourjik. Temperature is a global factor that affects the performance of all intracellular networks. Robustness against temperature variations is thus expected to be an essential network property, particula...."

Dynamic Analysis of Stochastic Transcription Cycles

Dynamic Analysis of Stochastic Transcription Cycles: "
Cycling of gene expression in individual cells is controlled by dynamic chromatin remodeling.
"

Exploring transcription regulation through cell-to-cell variability [Systems Biology]

Exploring transcription regulation through cell-to-cell variability [Systems Biology]: "The regulation of cellular protein levels is a complex process involving many regulatory mechanisms, each introducing stochastic events, leading to variability of protein levels between isogenic cells. Previous studies have shown that perturbing genes involved in transcription regulation affects the amount of cell-to-cell variability in protein levels, but to date there has been no systematic characterization of variability in expression as a phenotype. In this research, we use single-cell expression levels of two fluorescent reporters driven by two different promoters under a wide range of genetic perturbations in Saccharomyces cerevisiae, to identify proteins that affect variability in the expression of these reporters. We introduce computational methodology to determine the variability caused by each perturbation and distinguish between global variability, which affects both reporters in a coordinated manner (e.g., due to cell size variability), and local variability, which affects the individual reporters independently (e.g., due to stochastic events in transcription initiation). Classifying genes by their variability phenotype (the effect of their deletion on reporter variability) identifies functionally coherent groups, which broadly correlate with the different stages of transcriptional regulation. Specifically, we find that most processes whose perturbation affects global variability are related to protein synthesis, protein transport, and cell morphology, whereas most processes whose perturbations affect local variability are related to DNA maintenance, chromatin regulation, and RNA synthesis. Moreover, we demonstrate that the variability phenotypes of different protein complexes provide insights into their cellular functions. Our results establish the utility of variability phenotype for dissecting the regulatory mechanisms involved in gene expression."

Integrative analysis of genomic, functional and protein interaction data predicts long-range enhancer-target gene interactions

Integrative analysis of genomic, functional and protein interaction data predicts long-range enhancer-target gene interactions: "

Multicellular organismal development is controlled by a complex network of transcription factors, promoters and enhancers. Although reliable computational and experimental methods exist for enhancer detection, prediction of their target genes remains a major challenge. On the basis of available literature and ChIP-seq and ChIP-chip data for enhanceosome factor p300 and the transcriptional regulator Gli3, we found that genomic proximity and conserved synteny predict target genes with a relatively low recall of 12–27% within 2 Mb intervals centered at the enhancers. Here, we show that functional similarities between enhancer binding proteins and their transcriptional targets and proximity in the protein–protein interactome improve prediction of target genes. We used all four features to train random forest classifiers that predict target genes with a recall of 58% in 2 Mb intervals that may contain dozens of genes, representing a better than two-fold improvement over the performance of prediction based on single features alone. Genome-wide ChIP data is still relatively poorly understood, and it remains difficult to assign biological significance to binding events. Our study represents a first step in integrating various genomic features in order to elucidate the genomic network of long-range regulatory interactions.

"

What does biologically meaningful mean? A perspective on gene regulatory network validation

What does biologically meaningful mean? A perspective on gene regulatory network validation: "Gene regulatory networks (GRNs) are rapidly being delineated, but their quality and biological meaning are often questioned. Here, I argue that biological meaning is challenging to define and discuss reasons why GRN validation should be interpreted cautiously."

Proximodistal Patterning in the Drosophila Leg: Models and Mutations [Perspectives]

Proximodistal Patterning in the Drosophila Leg: Models and Mutations [Perspectives]: "

Limbs have a proximodistal axis that usually is not apparent early in development, a striking example of epigenesis. The proximodistal axis was the subject of experimental and theoretical study before any molecular genetic understanding emerged. As developmental genetic studies in Drosophila advanced, the descriptive polar coordinate model of the 1970s evolved into an understanding of how preexisting developmental compartments interact to express signaling molecules, including Hedgehog, Wingless, and Decapentaplegic, and how these define a proximodistal axis as limbs appear.

"

Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network

Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network: "Yen-Sin Ang, Su-Yi Tsai, Dung-Fang Lee, Jonathan Monk, Jie Su, Kajan Ratnakumar, Junjun Ding, Yongchao Ge, Henia Darr, Betty Chang, Jianlong Wang, Michael Rendl, Emily Bernstein, Christoph Schaniel, Ihor R. Lemischka. The embryonic stem (ES) cell transcriptional and chromatin-modifying networks are critical for self-renewal maintenance. However, it remains unclear whether these networks functionally interact an...."

Gene Duplication in Mimulus Underlies Parallel Floral Evolution via Independent trans-Regulatory Changes

Gene Duplication in Mimulus Underlies Parallel Floral Evolution via Independent trans-Regulatory Changes: "Arielle M. Cooley, Jennifer L. Modliszewski, Megan L. Rommel, John H. Willis. Identifying the genetic basis of parallelism reveals the means by which evolution repeats itself and shows what aspects—if any—may be predictable [1]. The recently tetraploid luteus group o...."

The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding

The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding: "Background:
In Drosophila embryos, many biochemically and functionally unrelated transcription factors bind quantitatively to highly overlapping sets of genomic regions, with much of the lowest levels of binding being incidental, non-functional interactions on DNA. The primary biochemical mechanisms that drive these genome-wide occupancy patterns have yet to be established.
Results:
Here we use data resulting from the DNaseI digestion of isolated embryo nuclei to provide a biophysical measure of the degree to which proteins can access different regions of the genome. We show that the in vivo binding patterns of 21 developmental regulators are quantitatively correlated with DNA accessibility in chromatin. Furthermore, we find that levels of factor occupancy in vivo correlate much more with the degree of chromatin accessibility than with occupancy predicted from in vitro affinity measurements using purified protein and naked DNA. Within accessible regions, however, the intrinsic affinity of the factor for DNA does play a role in determining net occupancy, with even weak affinity recognition sites contributing. Finally, we show that programmed changes in chromatin accessibility between different developmental stages correlate with quantitative alterations in factor binding.
Conclusions:
Based on these and other results, we propose a general mechanism to explain the widespread, overlapping DNA binding by animal transcription factors. In this view, transcription factors are expressed at sufficiently high concentrations in cells such that they can occupy their recognition sequences in highly accessible chromatin without the aid of physical cooperative interactions with other proteins, leading to highly overlapping, graded binding of unrelated factors."

RECOMBINATION AND HITCHHIKING OF DELETERIOUS ALLELES

RECOMBINATION AND HITCHHIKING OF DELETERIOUS ALLELES: "

ABSTRACT

When new advantageous alleles arise and spread within a population, deleterious alleles at neighbouring loci can hitchhike alongside them and spread to fixation in areas of low recombination, introducing a fixed mutation load. We use branching processes and diffusion equations to calculate the probability that a deleterious allele hitchhikes and fixes alongside an advantageous mutant. As expected, the probability of fixation of a deleterious hitchhiker rises with the selective advantage of the sweeping allele and declines with the selective disadvantage of the deleterious hitchhiker. We then use computer simulations of a genome with an infinite number of loci to investigate the increase in load after an advantageous mutant is introduced. We show that the appearance of advantageous alleles on genetic backgrounds loaded with deleterious alleles has two potential effects: it can fix deleterious alleles and also facilitate the persistence of recombinant lineages that happen to occur. The latter is expected to reduce the signals of selection in the surrounding region. We consider these results in light of human genetic data to infer how likely it is that such deleterious hitchhikers have occurred in our recent evolutionary past.

"

A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression

A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression: "

A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression

Nature 472, 7341 (2011). doi:10.1038/nature09819

Authors: Kevin C. Wang, Yul W. Yang, Bo Liu, Amartya Sanyal, Ryan Corces-Zimmerman, Yong Chen, Bryan R. Lajoie, Angeline Protacio, Ryan A. Flynn, Rajnish A. Gupta, Joanna Wysocka, Ming Lei, Job Dekker, Jill A. Helms & Howard Y. Chang

The genome is extensively transcribed into long intergenic noncoding RNAs (lincRNAs), many of which are implicated in gene silencing. Potential roles of lincRNAs in gene activation are much less understood. Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control. Some locus control elements and enhancers transcribe lincRNAs, hinting at possible roles in long-range control. In vertebrates, 39 Hox genes, encoding homeodomain transcription factors critical for positional identity, are clustered in four chromosomal loci; the Hox genes are expressed in nested anterior-posterior and proximal-distal patterns colinear with their genomic position from 3′ to 5′of the cluster. Here we identify HOTTIP, a lincRNA transcribed from the 5′ tip of the HOXA locus that coordinates the activation of several 5′ HOXA genes in vivo. Chromosomal looping brings HOTTIP into close proximity to its target genes. HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. Induced proximity is necessary and sufficient for HOTTIP RNA activation of its target genes. Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, lincRNAs may organize chromatin domains to coordinate long-range gene activation.

"

Tumour evolution inferred by single-cell sequencing

Tumour evolution inferred by single-cell sequencing: "

Tumour evolution inferred by single-cell sequencing

Nature 472, 7341 (2011). doi:10.1038/nature09807

Authors: Nicholas Navin, Jude Kendall, Jennifer Troge, Peter Andrews, Linda Rodgers, Jeanne McIndoo, Kerry Cook, Asya Stepansky, Dan Levy, Diane Esposito, Lakshmi Muthuswamy, Alex Krasnitz, W. Richard McCombie, James Hicks & Michael Wigler

Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse ‘pseudodiploid’ cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.

"

Subcellular in vivo time-lapse imaging and optical manipulation of Caenorhabditis elegans in standard multiwell plates

Subcellular in vivo time-lapse imaging and optical manipulation of Caenorhabditis elegans in standard multiwell plates: "

Subcellular in vivo time-lapse imaging and optical manipulation of Caenorhabditis elegans in standard multiwell plates

Nature Communications 2, 271 (2011). doi:10.1038/ncomms1266

Authors: Christopher B. Rohde & Mehmet Fatih Yanik

"

Genetic basis of eye and pigment loss in the cave crustacean, Asellus aquaticus [Evolution]

Genetic basis of eye and pigment loss in the cave crustacean, Asellus aquaticus [Evolution]: "Understanding the process of evolution is one of the great challenges in biology. Cave animals are one group with immense potential to address the mechanisms of evolutionary change. Amazingly, similar morphological alterations, such as enhancement of sensory systems and the loss of eyes and pigmentation, have evolved multiple times in a diverse assemblage of cave animals. Our goal is to develop an invertebrate model to study cave evolution so that, in combination with a previously established vertebrate cave system, we can address genetic questions concerning evolutionary parallelism and convergence. We chose the isopod crustacean, Asellus aquaticus, and generated a genome-wide linkage map for this species. Our map, composed of 117 markers, of which the majority are associated with genes known to be involved in pigmentation, eye, and appendage development, was used to identify loci of large effect responsible for several pigmentation traits and eye loss. Our study provides support for the prediction that significant morphological change can be mediated through one or a few genes. Surprisingly, we found that within population variability in eye size occurs through multiple mechanisms; eye loss has a different genetic basis than reduced eye size. Similarly, again within a population, the phenotype of albinism can be achieved by two different genetic pathways—either by a recessive genotype at one locus or doubly recessive genotypes at two other loci. Our work shows the potential of Asellus for studying the extremes of parallel and convergent evolution—spanning comparisons within populations to comparisons between vertebrate and arthropod systems."

Episodic radiations in the fly tree of life [Evolution]

Episodic radiations in the fly tree of life [Evolution]: "Flies are one of four superradiations of insects (along with beetles, wasps, and moths) that account for the majority of animal life on Earth. Diptera includes species known for their ubiquity (Musca domestica house fly), their role as pests (Anopheles gambiae malaria mosquito), and their value as model organisms across the biological sciences (Drosophila melanogaster). A resolved phylogeny for flies provides a framework for genomic, developmental, and evolutionary studies by facilitating comparisons across model organisms, yet recent research has suggested that fly relationships have been obscured by multiple episodes of rapid diversification. We provide a phylogenomic estimate of fly relationships based on molecules and morphology from 149 of 157 families, including 30 kb from 14 nuclear loci and complete mitochondrial genomes combined with 371 morphological characters. Multiple analyses show support for traditional groups (Brachycera, Cyclorrhapha, and Schizophora) and corroborate contentious findings, such as the anomalous Deuterophlebiidae as the sister group to all remaining Diptera. Our findings reveal that the closest relatives of the Drosophilidae are highly modified parasites (including the wingless Braulidae) of bees and other insects. Furthermore, we use micro-RNAs to resolve a node with implications for the evolution of embryonic development in Diptera. We demonstrate that flies experienced three episodes of rapid radiation—lower Diptera (220 Ma), lower Brachycera (180 Ma), and Schizophora (65 Ma)—and a number of life history transitions to hematophagy, phytophagy, and parasitism in the history of fly evolution over 260 million y."

Tradeoffs associated with constitutive and induced plant resistance against herbivory [Evolution]

Tradeoffs associated with constitutive and induced plant resistance against herbivory [Evolution]: "Several prominent hypotheses have been posed to explain the immense variability among plant species in defense against herbivores. A major concept in the evolutionary ecology of plant defenses is that tradeoffs of defense strategies are likely to generate and maintain species diversity. In particular, tradeoffs between constitutive and induced resistance and tradeoffs relating these strategies to growth and competitive ability have been predicted. We performed three independent experiments on 58 plant species from 15 different plant families to address these hypotheses in a phylogenetic framework. Because evolutionary tradeoffs may be altered by human-imposed artificial selection, we used 18 wild plant species and 40 cultivated garden-plant species. Across all 58 plant species, we demonstrate a tradeoff between constitutive and induced resistance, which was robust to accounting for phylogenetic history of the species. Moreover, the tradeoff was driven by wild species and was not evident for cultivated species. In addition, we demonstrate that more competitive species—but not fast growing ones—had lower constitutive but higher induced resistance. Thus, our multispecies experiments indicate that the competition–defense tradeoff holds for constitutive resistance and is complemented by a positive relationship of competitive ability with induced resistance. We conclude that the studied genetically determined tradeoffs are indeed likely to play an important role in shaping the high diversity observed among plant species in resistance against herbivores and in life history traits."

Draft genome of the globally widespread and invasive Argentine ant (Linepithema humile) [Evolution]

Draft genome of the globally widespread and invasive Argentine ant (Linepithema humile) [Evolution]: "Ants are some of the most abundant and familiar animals on Earth, and they play vital roles in most terrestrial ecosystems. Although all ants are eusocial, and display a variety of complex and fascinating behaviors, few genomic resources exist for them. Here, we report the draft genome sequence of a particularly widespread and well-studied species, the invasive Argentine ant (Linepithema humile), which was accomplished using a combination of 454 (Roche) and Illumina sequencing and community-based funding rather than federal grant support. Manual annotation of >1,000 genes from a variety of different gene families and functional classes reveals unique features of the Argentine ant's biology, as well as similarities to Apis mellifera and Nasonia vitripennis. Distinctive features of the Argentine ant genome include remarkable expansions of gustatory (116 genes) and odorant receptors (367 genes), an abundance of cytochrome P450 genes (>110), lineage-specific expansions of yellow/major royal jelly proteins and desaturases, and complete CpG DNA methylation and RNAi toolkits. The Argentine ant genome contains fewer immune genes than Drosophila and Tribolium, which may reflect the prominent role played by behavioral and chemical suppression of pathogens. Analysis of the ratio of observed to expected CpG nucleotides for genes in the reproductive development and apoptosis pathways suggests higher levels of methylation than in the genome overall. The resources provided by this genome sequence will offer an abundance of tools for researchers seeking to illuminate the fascinating biology of this emerging model organism."

Draft genome of the red harvester ant Pogonomyrmex barbatus [Evolution]

Draft genome of the red harvester ant Pogonomyrmex barbatus [Evolution]: "We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome was sequenced using 454 pyrosequencing, and the current assembly and annotation were completed in less than 1 y. Analyses of conserved gene groups (more than 1,200 manually annotated genes to date) suggest a high-quality assembly and annotation comparable to recently sequenced insect genomes using Sanger sequencing. The red harvester ant is a model for studying reproductive division of labor, phenotypic plasticity, and sociogenomics. Although the genome of P. barbatus is similar to other sequenced hymenopterans (Apis mellifera and Nasonia vitripennis) in GC content and compositional organization, and possesses a complete CpG methylation toolkit, its predicted genomic CpG content differs markedly from the other hymenopterans. Gene networks involved in generating key differences between the queen and worker castes (e.g., wings and ovaries) show signatures of increased methylation and suggest that ants and bees may have independently co-opted the same gene regulatory mechanisms for reproductive division of labor. Gene family expansions (e.g., 344 functional odorant receptors) and pseudogene accumulation in chemoreception and P450 genes compared with A. mellifera and N. vitripennis are consistent with major life-history changes during the adaptive radiation of Pogonomyrmex spp., perhaps in parallel with the development of the North American deserts."

Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart [Developmental Biology]

Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart [Developmental Biology]: "Identification of genomic regions that control tissue-specific gene expression is currently problematic. ChIP and high-throughput sequencing (ChIP-seq) of enhancer-associated proteins such as p300 identifies some but not all enhancers active in a tissue. Here we show that co-occupancy of a chromatin region by multiple transcription factors (TFs) identifies a distinct set of enhancers. GATA-binding protein 4 (GATA4), NK2 transcription factor-related, locus 5 (NKX2-5), T-box 5 (TBX5), serum response factor (SRF), and myocyte-enhancer factor 2A (MEF2A), here referred to as “cardiac TFs,” have been hypothesized to collaborate to direct cardiac gene expression. Using a modified ChIP-seq procedure, we defined chromatin occupancy by these TFs and p300 genome wide and provided unbiased support for this hypothesis. We used this principle to show that co-occupancy of a chromatin region by multiple TFs can be used to identify cardiac enhancers. Of 13 such regions tested in transient transgenic embryos, seven (54%) drove cardiac gene expression. Among these regions were three cardiac-specific enhancers of Gata4, Srf, and swItch/sucrose nonfermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3 (Smarcd3), an epigenetic regulator of cardiac gene expression. Multiple cardiac TFs and p300-bound regions were associated with cardiac-enriched genes and with functional annotations related to heart development. Importantly, the large majority (1,375/1,715) of loci bound by multiple cardiac TFs did not overlap loci bound by p300. Our data identify thousands of prospective cardiac regulatory sequences and indicate that multiple TF co-occupancy of a genomic region identifies developmentally relevant enhancers that are largely distinct from p300-associated enhancers."

Polycomb purification by in vivo biotinylation tagging reveals cohesin and Trithorax group proteins as interaction partners [Biochemistry]

Polycomb purification by in vivo biotinylation tagging reveals cohesin and Trithorax group proteins as interaction partners [Biochemistry]: "The maintenance of specific gene expression patterns during cellular proliferation is crucial for the identity of every cell type and the development of tissues in multicellular organisms. Such a cellular memory function is conveyed by the complex interplay of the Polycomb and Trithorax groups of proteins (PcG/TrxG). These proteins exert their function at the level of chromatin by establishing and maintaining repressed (PcG) and active (TrxG) chromatin domains. Past studies indicated that a core PcG protein complex is potentially associated with cell type or even cell stage-specific sets of accessory proteins. In order to better understand the dynamic aspects underlying PcG composition and function we have established an inducible version of the biotinylation tagging approach to purify Polycomb and associated factors from Drosophila embryos. This system enabled fast and efficient isolation of Polycomb containing complexes under near physiological conditions, thereby preserving substoichiometric interactions. Novel interacting proteins were identified by highly sensitive mass spectrometric analysis. We found many TrxG related proteins, suggesting a previously unrecognized extent of molecular interaction of the two counteracting chromatin regulatory protein groups. Furthermore, our analysis revealed an association of PcG protein complexes with the cohesin complex and showed that Polycomb-dependent silencing of a transgenic reporter depends on cohesin function."

STOCHASTICITY IN REPRODUCTIVE OPPORTUNITY AND THE EVOLUTION OF EGG LIMITATION IN INSECTS

STOCHASTICITY IN REPRODUCTIVE OPPORTUNITY AND THE EVOLUTION OF EGG LIMITATION IN INSECTS: "

ABSTRACT

Is reproduction by adult female insects limited by the finite time available to locate hosts (‘time limitation’) or by the finite supply of eggs (‘egg limitation’)? An influential model predicted that stochasticity in reproductive opportunity favors elevated fecundity, rendering egg limitation sufficiently rare that its importance would be greatly diminished. Here I use models to explore how stochasticity shapes fecundity, the likelihood of egg limitation, and the ecological importance of egg limitation. The models make three predictions. First, whereas spatially stochastic environments favor increased fecundity, temporally stochastic environments favor increases, decreases, or intermediate maxima in fecundity, depending on egg costs. Second, even when spatially or temporally stochastic environments favor life histories with less frequent egg limitation, stochasticity still increases the proportion of all eggs laid in the population that is laid by females destined to become egg limited. This counterintuitive result is explained by noting that stochasticity concentrates reproduction in the hands of a few females that are likely to become egg limited. Third, spatially or temporally stochastic environments amplify the constraints imposed by time and eggs on total reproduction by the population. I conclude that both egg and time constraints are fundamental in shaping insect reproductive behavior and population dynamics in stochastic environments.

"

EVOLUTION OF MALE AND FEMALE GENITALIA FOLLOWING RELEASE FROM SEXUAL SELECTION

EVOLUTION OF MALE AND FEMALE GENITALIA FOLLOWING RELEASE FROM SEXUAL SELECTION: "

ABSTRACT

Despite the key functions of the genitalia in sexual interactions and fertilization, the role of sexual selection and conflict in shaping genital traits remains poorly understood. Seed beetle (Callosobruchus maculatus) males possess spines on the intromittent organ, and females possess a thickened reproductive tract wall that also bears spines. We investigated the role of sexual selection and conflict by imposing monogamous mating on eight replicate populations of this naturally polygamous insect, while maintaining eight other populations under polygamy. To establish whether responses to mating system manipulation were robust to ecological context, we simultaneously manipulated life history selection (early/late reproduction). Over 18–21 generations, male genital spines evolved relatively reduced length in large males (i.e., shallower static allometry) in monogamous populations. Two non-intromittent male genital appendages also evolved in response to the interaction of mating system and ecology. In contrast, no detectable evolution occurred in female genitalia, consistent with the expectation of a delayed response in defensive traits. Our results support a sexually antagonistic role for the male genital spines, and demonstrate the evolution of static allometry in response to variation in sexual selection opportunity. We argue that further advances in the study of genital coevolution will require a much more detailed understanding of the functions of male and female genital traits.

"

Sequence-based physical mapping of complex genomes by whole genome profiling [METHOD]

Sequence-based physical mapping of complex genomes by whole genome profiling [METHOD]: "

We present whole genome profiling (WGP), a novel next-generation sequencing-based physical mapping technology for construction of bacterial artificial chromosome (BAC) contigs of complex genomes, using Arabidopsis thaliana as an example. WGP leverages short read sequences derived from restriction fragments of two-dimensionally pooled BAC clones to generate sequence tags. These sequence tags are assigned to individual BAC clones, followed by assembly of BAC contigs based on shared regions containing identical sequence tags. Following in silico analysis of WGP sequence tags and simulation of a map of Arabidopsis chromosome 4 and maize, a WGP map of Arabidopsis thaliana ecotype Columbia was constructed de novo using a six-genome equivalent BAC library. Validation of the WGP map using the Columbia reference sequence confirmed that 350 BAC contigs (98%) were assembled correctly, spanning 97% of the 102-Mb calculated genome coverage. We demonstrate that WGP maps can also be generated for more complex plant genomes and will serve as excellent scaffolds to anchor genetic linkage maps and integrate whole genome sequence data.

"

Multiplexed shotgun genotyping for rapid and efficient genetic mapping [METHOD]

Multiplexed shotgun genotyping for rapid and efficient genetic mapping [METHOD]: "

We present a new approach to genotyping based on multiplexed shotgun sequencing that can identify recombination breakpoints in a large number of individuals simultaneously at a resolution sufficient for most mapping purposes, such as quantitative trait locus (QTL) mapping and mapping of induced mutations. We first describe a simple library construction protocol that uses just 10 ng of genomic DNA per individual and makes the approach accessible to any laboratory with standard molecular biology equipment. Sequencing this library results in a large number of sequence reads widely distributed across the genomes of multiplexed bar-coded individuals. We develop a Hidden Markov Model to estimate ancestry at all genomic locations in all individuals using these data. We demonstrate the utility of the approach by mapping a dominant marker allele in D. simulans to within 105 kb of its true position using 96 F1-backcross individuals genotyped in a single lane on an Illumina Genome Analyzer. We further demonstrate the utility of our method by genetically mapping more than 400 previously unassembled D. simulans contigs to linkage groups and by evaluating the quality of targeted introgression lines. At this level of multiplexing and divergence between strains, our method allows estimation of recombination breakpoints to a median of 38-kb intervals. Our analysis suggests that higher levels of multiplexing and/or use of strains with lower levels of divergence are practicable.

"

Coordinated histone modifications are associated with gene expression variation within and between species [RESEARCH]

Coordinated histone modifications are associated with gene expression variation within and between species [RESEARCH]: "

Histone modifications regulate gene expression in eukaryotes, but their effects on transcriptomes of a multicellular organism and on transcriptomic divergence between species are poorly understood. Here we present the first nucleotide-resolution maps of histone acetylation, methylation, and core histone in Arabidopsis thaliana and a comprehensive analysis of these and all other available maps with gene expression data in A. thaliana, Arabidopsis arenosa, and allotetraploids. H3K9 acetylation (H3K9ac) and H3K4 trimethylation (H3K4me3) are correlated, and their distribution patterns are associated with Gene Ontology (GO) functional classifications. Highly dense and narrow distributions of these modifications near transcriptional start sites are associated with constitutive expression of genes involved in translation, whereas broad distributions toward coding regions correlate with expression variation of the genes involved in photosynthesis, carbohydrate metabolism, and defense responses. Compared to animal stem cells, dispersed distributions of H3K27me3 without bivalent H3K4me3 and H3K9ac marks correlate with developmentally repressed genes in Arabidopsis. Finally, genes affected by A. thaliana histone deacetylase 1 mutation tend to show high levels of expression variation within and between species. The data suggest that genome-wide coordinated modifications of histone acetylation and methylation provide a general mechanism for gene expression changes within and between species and in allopolyploids.

"

Genes for embryo development are packaged in blocks of multivalent chromatin in zebrafish sperm [RESEARCH]

Genes for embryo development are packaged in blocks of multivalent chromatin in zebrafish sperm [RESEARCH]: "

In mature human sperm, genes of importance for embryo development (i.e., transcription factors) lack DNA methylation and bear nucleosomes with distinctive histone modifications, suggesting the specialized packaging of these developmental genes in the germline. Here, we explored the tractable zebrafish model and found conceptual conservation as well as several new features. Biochemical and mass spectrometric approaches reveal the zebrafish sperm genome packaged in nucleosomes and histone variants (and not protamine), and we find linker histones high and H4K16ac absent, key factors that may contribute to genome condensation. We examined several activating (H3K4me2/3, H3K14ac, H2AFV) and repressing (H3K27me3, H3K36me3, H3K9me3, hypoacetylation) modifications/compositions genome-wide and find developmental genes packaged in large blocks of chromatin with coincident activating and repressing marks and DNA hypomethylation, revealing complex 'multivalent' chromatin. Notably, genes that acquire DNA methylation in the soma (muscle) are enriched in transcription factors for alternative cell fates. Remarkably, whereas H3K36me3 is located in the 3' coding region of heavily transcribed genes in somatic cells, H3K36me3 is present in the promoters of 'silent' developmental regulators in sperm, suggesting different rules for H3K36me3 in the germline and soma. We also reveal the chromatin patterns of transposons, rDNA, and tDNAs. Finally, high levels of H3K4me3 and H3K14ac in sperm are correlated with genes activated in embryos prior to the mid-blastula transition (MBT), whereas multivalent genes are correlated with activation at or after MBT. Taken together, gene sets with particular functions in the embryo are packaged by distinctive types of complex and often atypical chromatin in sperm.

"

High resolution mapping of Twist to DNA in Drosophila embryos: Efficient functional analysis and evolutionary conservation [RESEARCH]

High resolution mapping of Twist to DNA in Drosophila embryos: Efficient functional analysis and evolutionary conservation [RESEARCH]: "

Cis-regulatory modules (CRMs) function by binding sequence specific transcription factors, but the relationship between in vivo physical binding and the regulatory capacity of factor-bound DNA elements remains uncertain. We investigate this relationship for the well-studied Twist factor in Drosophila melanogaster embryos by analyzing genome-wide factor occupancy and testing the functional significance of Twist occupied regions and motifs within regions. Twist ChIP-seq data efficiently identified previously studied Twist-dependent CRMs and robustly predicted new CRM activity in transgenesis, with newly identified Twist-occupied regions supporting diverse spatiotemporal patterns (>74% positive, n = 31). Some, but not all, candidate CRMs require Twist for proper expression in the embryo. The Twist motifs most favored in genome ChIP data (in vivo) differed from those most favored by Systematic Evolution of Ligands by EXponential enrichment (SELEX) (in vitro). Furthermore, the majority of ChIP-seq signals could be parsimoniously explained by a CABVTG motif located within 50 bp of the ChIP summit and, of these, CACATG was most prevalent. Mutagenesis experiments demonstrated that different Twist E-box motif types are not fully interchangeable, suggesting that the ChIP-derived consensus (CABVTG) includes sites having distinct regulatory outputs. Further analysis of position, frequency of occurrence, and sequence conservation revealed significant enrichment and conservation of CABVTG E-box motifs near Twist ChIP-seq signal summits, preferential conservation of ±150 bp surrounding Twist occupied summits, and enrichment of GA- and CA-repeat sequences near Twist occupied summits. Our results show that high resolution in vivo occupancy data can be used to drive efficient discovery and dissection of global and local cis-regulatory logic.

"

Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers [RESEARCH]

Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers [RESEARCH]: "

Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established. Here, we have analyzed on a genomic-scale enhancers that recruit FOXA1, a pioneer transcription factor that triggers transcriptional competency of these cis-regulatory sites. Importantly, we found that FOXA1 binds to genomic regions showing local DNA hypomethylation and that its cell-type-specific recruitment to chromatin is linked to differential DNA methylation levels of its binding sites. Using neural differentiation as a model, we showed that induction of FOXA1 expression and its subsequent recruitment to enhancers is associated with DNA demethylation. Concomitantly, histone H3 lysine 4 methylation is induced at these enhancers. These epigenetic changes may both stabilize FOXA1 binding and allow for subsequent recruitment of transcriptional regulatory effectors. Interestingly, when cloned into reporter constructs, FOXA1-dependent enhancers were able to recapitulate their cell type specificity. However, their activities were inhibited by DNA methylation. Hence, these enhancers are intrinsic cell-type-specific regulatory regions of which activities have to be potentiated by FOXA1 through induction of an epigenetic switch that includes notably DNA demethylation.

"

Molecular Architecture of the Human Mediator–RNA Polymerase II–TFIIF Assembly

Molecular Architecture of the Human Mediator–RNA Polymerase II–TFIIF Assembly: "

The authors perform a cryo-EM study of the 1.9 MDa human Mediator-RNA polymerase II-TFIIF assembly, which reveals the structural organization of the human transcription initiation apparatus.

"

A Simple Mechanism for Complex Social Behavior

A Simple Mechanism for Complex Social Behavior: "Author Summary

Despite the appearance of cooperation in nature, selection should often favor exploitative individuals who perform less of any cooperative behaviors while maintaining the benefits accrued from the cooperative behavior of others. This conflict of interest among cooperating individuals can lead to the evolution of complex social strategies that depend on the identity (e.g. genotype or strategy) of the individuals with whom you interact. The social amoeba Dictyostelium discoideum provides a compelling model for studying such “partner specific” conflict and cooperation. Upon starvation, free-living amoebae aggregate and form a fruiting body composed of dead stalk cells and hardy spores. Different genotypes will aggregate to produce chimeric fruiting bodies, resulting in potential social conflict over who will contribute to the reproductive sporehead and who will “sacrifice” themselves to produce the dead stalk. The outcomes of competitive interactions in chimera appear complex, with social success being strongly partner specific. Here we propose a simple mechanism to explain social strategies in D. discoideum, based on the production of and response to stalk-inducing factors, the social signals that determine whether cells become stalk or spore. Indeed, measurements of signal production and response can predict social behavior of different strains, thus demonstrating a novel and elegantly simple underlying mechanistic basis for natural variation in complex facultative social strategies. This suggests that simple social rules can be sufficient to generate a diverse array of behavioral outcomes that appear complex and unpredictable when those rules are unknown.

"

H3 Lysine 4 Is Acetylated at Active Gene Promoters and Is Regulated by H3 Lysine 4 Methylation

H3 Lysine 4 Is Acetylated at Active Gene Promoters and Is Regulated by H3 Lysine 4 Methylation: "Author Summary

In the nucleus of mammals and yeast, DNA is packaged by forming complexes with histone proteins in a structure called the nucleosome, the basic building block of chromatin. The tails of the histones protrude from the nucleosome and can be marked on many amino acid residues by chemical modifications such as methylation and acetylation. A highly studied modification, which is robustly associated with active gene promoters, is histone H3 lysine 4 methylation. We describe here a novel modification, histone H3 lysine 4 acetylation (H3K4ac), which can occur on the same lysine of the histone H3 tail (but not at the same time as methylation). We have identified the enzymes responsible for depositing and removing this mark and mapped its distribution throughout the yeast genome. We found that H3K4ac is present on active genes and is important for the full expression of a subset of them. Strikingly, H3K4 methylation was found in the same promoters as H3K4ac and contributes to regulate the abundance and localisation of H3K4ac. This example of cross-talk between two different modifications of the same residue has fundamental implications for understanding how genes are activated and how their packaging in the nucleus controls this process.

"

Systematic Detection of Polygenic cis-Regulatory Evolution

Systematic Detection of Polygenic cis-Regulatory<br> Evolution: "Author Summary

Evolution can involve changes that are advantageous—known as
adaptations—as well as changes that are neutral or slightly deleterious,
which are established through a process of random drift. Discerning what
specific differences between any two lineages are adaptive is a major goal of
evolutionary biology. For gene expression differences, this has traditionally
proven to be a challenging question, and previous studies of gene expression
adaptation in metazoans have been restricted to the single-gene level. Here we
present a genome-wide analysis of gene expression evolution in two subspecies of
the mouse Mus musculus. We find several groups of genes that
have likely been subject to selection for up-regulation in a specific lineage.
These groups include genes related to mitochondria, growth, locomotion, and
memory. Analysis of the phenotypes of these mice indicates that these
adaptations may have had a significant impact on a wide range of phenotypes.

"