Evolutionary Origin of the Turtle Shell

Evolutionary Origin of the Turtle Shell: Tyler R. Lyson, Gabe S. Bever, Torsten M. Scheyer, Allison Y. Hsiang, Jacques A. Gauthier.

 The origin of the turtle shell has perplexed biologists for more than two centuries [1]. It was not until Odontochelys semitestacea [2] was discovered, however, that the fossil and developm....

[Report] Functional Extinction of Birds Drives Rapid Evolutionary Changes in Seed Size

[Report] Functional Extinction of Birds Drives Rapid Evolutionary Changes in Seed Size: Local extinction of large fruit-eating birds selects for reduction of seed size in a tropical forest palm.

Authors: Mauro Galetti, Roger Guevara, Marina C. Côrtes, Rodrigo Fadini, Sandro Von Matter, Abraão B. Leite, Fábio Labecca, Thiago Ribeiro, Carolina S. Carvalho, Rosane G. Collevatti, Mathias M. Pires, Paulo R. Guimarães Jr., Pedro H. Brancalion, Milton C. Ribeiro, Pedro Jordano

Strong Purifying Selection at Synonymous Sites in D. melanogaster

Strong Purifying Selection at Synonymous Sites in D. melanogaster:
by David S. Lawrie, Philipp W. Messer, Ruth Hershberg, Dmitri A. Petrov

Synonymous sites are generally assumed to be subject to weak selective constraint. For this reason, they are often neglected as a possible source of important functional variation. We use site frequency spectra from deep population sequencing data to show that, contrary to this expectation, 22% of four-fold synonymous (4D) sites in Drosophila melanogaster evolve under very strong selective constraint while few, if any, appear to be under weak constraint. Linking polymorphism with divergence data, we further find that the fraction of synonymous sites exposed to strong purifying selection is higher for those positions that show slower evolution on the Drosophila phylogeny. The function underlying the inferred strong constraint appears to be separate from splicing enhancers, nucleosome positioning, and the translational optimization generating canonical codon bias. The fraction of synonymous sites under strong constraint within a gene correlates well with gene expression, particularly in the mid-late embryo, pupae, and adult developmental stages. Genes enriched in strongly constrained synonymous sites tend to be particularly functionally important and are often involved in key developmental pathways. Given that the observed widespread constraint acting on synonymous sites is likely not limited to Drosophila, the role of synonymous sites in genetic disease and adaptation should be reevaluated.

Drosophila Functional Elements Are Embedded in Structurally Constrained Sequences

Drosophila Functional Elements Are Embedded in Structurally Constrained Sequences:
by Ephraim Kenigsberg, Amos Tanay

Modern functional genomics uncovered numerous functional elements in metazoan genomes. Nevertheless, only a small fraction of the typical non-exonic genome contains elements that code for function directly. On the other hand, a much larger fraction of the genome is associated with significant evolutionary constraints, suggesting that much of the non-exonic genome is weakly functional. Here we show that in flies, local (30–70 bp) conserved sequence elements that are associated with multiple regulatory functions serve as focal points to a pattern of punctuated regional increase in G/C nucleotide frequencies. We show that this pattern, which covers a region tenfold larger than the conserved elements themselves, is an evolutionary consequence of a shift in the balance between gain and loss of G/C nucleotides and that it is correlated with nucleosome occupancy across multiple classes of epigenetic state. Evidence for compensatory evolution and analysis of SNP allele frequencies show that the evolutionary regime underlying this balance shift is likely to be non-neutral. These data suggest that current gaps in our understanding of genome function and evolutionary dynamics are explicable by a model of sparse sequence elements directly encoding for function, embedded into structural sequences that help to define the local and global epigenomic context of such functional elements.

Absolute quantification of transcription factors during cellular differentiation using multiplexed targeted proteomics

Absolute quantification of transcription factors during cellular differentiation using multiplexed targeted proteomics:
Nature Methods 10, 570 (2013).
doi:10.1038/nmeth.2441

Authors: Jovan Simicevic, Adrien W Schmid, Paola A Gilardoni, Benjamin Zoller, Sunil K Raghav, Irina Krier, Carine Gubelmann, Frédérique Lisacek, Felix Naef, Marc Moniatte & Bart Deplancke

The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan

The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan:
Nature Genetics 45, 701 (2013).
doi:10.1038/ng.2615

Authors: Zhuo Wang, Juan Pascual-Anaya, Amonida Zadissa, Wenqi Li, Yoshihito Niimura, Zhiyong Huang, Chunyi Li, Simon White, Zhiqiang Xiong, Dongming Fang, Bo Wang, Yao Ming, Yan Chen, Yuan Zheng, Shigehiro Kuraku, Miguel Pignatelli, Javier Herrero, Kathryn Beal, Masafumi Nozawa, Qiye Li, Juan Wang, Hongyan Zhang, Lili Yu, Shuji Shigenobu, Junyi Wang, Jiannan Liu, Paul Flicek, Steve Searle, Jun Wang, Shigeru Kuratani, Ye Yin, Bronwen Aken, Guojie Zhang & Naoki Irie
The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ∼267.9–248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell.

Human frontal lobe size [Evolution]

Human frontal lobe size [Evolution]: One of the most pervasive assumptions about human brain evolution is that it involved relative enlargement of the frontal lobes. We show that this assumption is without foundation. Analysis of five independent data sets using correctly scaled measures and phylogenetic methods reveals that the size of human frontal lobes, and...

The Genetic Basis of White Tigers

The Genetic Basis of White Tigers: Xiao Xu, Gui-Xin Dong, Xue-Song Hu, Lin Miao, Xue-Li Zhang, De-Lu Zhang, Han-Dong Yang, Tian-You Zhang, Zheng-Ting Zou, Ting-Ting Zhang, Yan Zhuang, Jong Bhak, Yun Sung Cho, Wen-Tao Dai, Tai-Jiao Jiang, Can Xie, Ruiqiang Li, Shu-Jin Luo. The white tiger, an elusive Bengal tiger (Panthera tigris tigris) variant with white fur and dark stripes, has fascinated humans for centuries ever since its discovery in the jungles of Ind....

Paused Pol II Coordinates Tissue Morphogenesis in the Drosophila Embryo

Paused Pol II Coordinates Tissue Morphogenesis in the Drosophila Embryo: Mounia Lagha, Jacques P. Bothma, Emilia Esposito, Samuel Ng, Laura Stefanik, Chiahao Tsui, Jeffrey Johnston, Kai Chen, David S. Gilmour, Julia Zeitlinger, Michael S. Levine.

Paused RNA polymerase (Pol II) is a pervasive feature of Drosophila embryos and mammalian stem cells, but its role in development is uncertain. Here, we demonstrate that a spectrum of pause....

New Balance in Pluripotency: Reprogramming with Lineage Specifiers

New Balance in Pluripotency: Reprogramming with Lineage Specifiers: Uri Ben-David, Jonathan Nissenbaum, Nissim Benvenisty. Induction of pluripotency in somatic cells has been achieved by myriad combinations of transcription factors that belong to the core pluripotency circuitry. In this issue, Shu et al. report reprog....

GRN for neurogenesis in a sea star embryo [Developmental Biology]

GRN for neurogenesis in a sea star embryo [Developmental Biology]:

A great challenge in development biology is to understand how interacting networks of regulatory genes can direct the often highly complex patterning of cells in a 3D embryo. Here, we detail the gene regulatory network that describes the distribution of ciliary band-associated neurons in the bipinnaria larva of the sea...

Ultraconserved words [Anthropology]

Ultraconserved words [Anthropology]: The search for ever deeper relationships among the World’s languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some “ultraconserved” words exist that might be used to find...

Functional Interrogation of an Odorant Receptor Locus Reveals Multiple Axes of Transcriptional Regulation

Functional Interrogation of an Odorant Receptor Locus Reveals Multiple Axes of Transcriptional Regulation:
by Alexander Fleischmann, Ishmail Abdus-Saboor, Atef Sayed, Benjamin Shykind

The odorant receptor (OR) genes constitute the largest mammalian gene family and are expressed in a monogenic and monoallelic fashion, through an unknown mechanism that likely exploits positive and negative regulation. We devised a genetic strategy in mice to examine OR selection by determining the transcriptional activity of an exogenous promoter homologously integrated into an OR locus. Using the tetracycline-dependent transactivator responsive promoter (tet_o), we observed that the OR locus imposes spatial and temporal constraints on tet_o-driven transcription. Conditional expression experiments reveal a developmental change in the permissiveness of the locus. Further, expression of an OR transgene that suppresses endogenous ORs similarly represses the OR-integrated tet_o. Neurons homozygous for the tet_o-modified allele demonstrate predominantly monoallelic expression, despite their potential to express both copies. These data reveal multiple axes of regulation, and support a model of initiation of OR choice limited by nonpermissive chromatin and maintained by repression of nonselected alleles.

From neural development to cognition: unexpected roles for chromatin

From neural development to cognition: unexpected roles for chromatin:
Nature Reviews Genetics 14, 440 (2013).
doi:10.1038/nrg3508

Author: Jehnna L. Ronan, Wei Wu & Gerald R. Crabtree
Nature Reviews Genetics14, 347–359 (2013)In the above article, some of the references citations were incorrectly numbered in the 'Chromatin remodellers' section and in Table 1. This has now been corrected online. The editors apologize for this mistake.

Mechanisms and models of somatic cell reprogramming

Mechanisms and models of somatic cell reprogramming:
Nature Reviews Genetics 14, 427 (2013).
doi:10.1038/nrg3473

Authors: Yosef Buganim, Dina A. Faddah & Rudolf Jaenisch
Conversion of somatic cells to pluripotency by defined factors is a long and complex process that yields embryonic-stem-cell-like cells that vary in their developmental potential. To improve the quality of resulting induced pluripotent stem cells (iPSCs), which is important for potential therapeutic applications, and to

Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data

Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data:
Nature Reviews Genetics 14, 390 (2013).
doi:10.1038/nrg3454

Authors: Job Dekker, Marc A. Marti-Renom & Leonid A. Mirny
How DNA is organized in three dimensions inside the cell nucleus and how this affects the ways in which cells access, read and interpret genetic information are among the longest standing questions in cell biology. Using newly developed molecular, genomic and computational approaches based on

Development: Testing the threshold-dependent model

Development: Testing the threshold-dependent model:
Nature Reviews Genetics 14, 369 (2013).
doi:10.1038/nrg3512

Author: Hannah Stower
The threshold-dependent model predicts that morphogenesis programmes are executed by genetic networks that respond to absolute concentrations of transcription factors. To test this model, Liu et al. manipulated the absolute concentration of the transcription factor Bicoid in Drosophila melanogaster early embryos. Early on,

Tissue Repair through Cell Competition and Compensatory Cellular Hypertrophy in Postmitotic Epithelia

Tissue Repair through Cell Competition and Compensatory Cellular Hypertrophy in Postmitotic Epithelia: Yoichiro Tamori, Wu-Min Deng. In multicellular organisms, tissue integrity and organ size are maintained through removal of aberrant or damaged cells and compensatory proliferation. Little is known, however, about this homeost....

Genetic and developmental analysis of differences in eye and face morphology between Drosophila simulans and Drosophila mauritiana

Genetic and developmental analysis of differences in eye and face morphology between Drosophila simulans and Drosophila mauritiana:

SUMMARY

Eye and head morphology vary considerably among insects and even between closely related species of Drosophila. Species of the D. melanogaster subgroup, and other Drosophila species, exhibit a negative correlation between eye size and face width (FW); for example, D. mauritiana generally has bigger eyes composed of larger ommatidia and conversely a narrower face than its sibling species. To better understand the evolution of eye and head morphology, we investigated the genetic and developmental basis of differences in eye size and FW between male D. mauritiana and D. simulans. QTL mapping of eye size and FW showed that the major loci responsible for the interspecific variation in these traits are localized to different genomic regions. Introgression of the largest effect QTL underlying the difference in eye size resulted in flies with larger eyes but no significant difference in FW. Moreover, introgression of a QTL region on the third chromosome that contributes to the FW difference between these species affected FW, but not eye size. We also observed that this difference in FW is detectable earlier in the development of the eye-antennal disc than the difference in the size of the retinal field. Our results suggest that different loci that act at different developmental stages underlie changes in eye size and FW. Therefore, while there is a negative correlation between these traits in Drosophila, we show genetically that they also have the potential to evolve independently and this may help to explain the evolution of these traits in other insects.

Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer: Masahito Tachibana, Paula Amato, Michelle Sparman, Nuria Marti Gutierrez, Rebecca Tippner-Hedges, Hong Ma, Eunju Kang, Alimujiang Fulati, Hyo-Sang Lee, Hathaitip Sritanaudomchai, Keith Masterson, Janine Larson, Deborah Eaton, Karen Sadler-Fredd, David Battaglia, David Lee, Diana Wu, Jeffrey Jensen, Phillip Patton, Sumita Gokhale, Richard L. Stouffer, Don Wolf, Shoukhrat Mitalipov.

Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer ....

Adaptive dynamics under development-based genotype–phenotype maps

Adaptive dynamics under development-based genotype–phenotype maps:
Adaptive dynamics under development-based genotype–phenotype maps

Nature 497, 7449 (2013). doi:10.1038/nature12142

Authors: Isaac Salazar-Ciudad & Miquel Marín-Riera

It is not known whether natural selection can encounter any given phenotype that can be produced by genetic variation. There has been a long-lasting debate about the processes that limit adaptation and, consequently, about how well adapted phenotypes are. Here we examine how development may affect adaptation, by decomposing the genotype–fitness map—the association between each genotype and its fitness—into two: one mapping genotype to phenotype by means of a computational model of organ development, and one mapping phenotype to fitness. In the map of phenotype and fitness, the fitness of each individual is based on the similarity between realized morphology and optimal morphology. We use three different simulations to map phenotype to fitness, and these differ in the way in which similarity is calculated: similarity is calculated for each trait (in terms of each cell position individually), for a large or a small number of phenotypic landmarks (the ‘many-traits’ and ‘few-traits’ phenotype–fitness maps), and by measuring the overall surface roughness of morphology (the ‘roughness’ phenotype–fitness map). Evolution is simulated by applying the genotype–phenotype map and one phenotype–fitness map to each individual in the population, as well as random mutation and drift. We show that the complexity of the genotype–phenotype map prevents substantial adaptation in some of the phenotype–fitness maps: sustained adaptation is only possible using ‘roughness’ or ‘few-traits’ phenotype–fitness maps. The results contribute developmental understanding to the long-standing question of which aspects of phenotype can be effectively optimized by natural selection.

Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation

Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation:

Genomic structural alterations that vary within species, known as large copy number variants, represent an unanticipated and abundant source of genetic diversity that associates with variation in gene expression and susceptibility to disease. Even short insertions and deletions (indels) can exert important effects on genomes by locally increasing the mutation rate, with multiple mechanisms proposed to account for this pattern. To better understand how indels promote genome evolution, we demonstrate that the single nucleotide mutation rate is elevated in the vicinity of indels, with a resolution of tens of base pairs, for the two closely related nematode species Caenorhabditis remanei and C. sp. 23. In addition to indels being clustered with single nucleotide polymorphisms and fixed differences, we also show that transversion mutations are enriched in sequences that flank indels and that many indels associate with sequence repeats. These observations are compatible with a model that reconciles previously proposed mechanisms of indel-associated mutagenesis, implicating repeat sequences as a common driver of indel errors, which then recruit error-prone polymerases during DNA repair, resulting in a locally elevated single nucleotide mutation rate. The striking influence of indel variants on the molecular evolution of flanking sequences strengthens the emerging general view that mutations can induce further mutations.

The rate of evolution

The rate of evolution:
Ecological factors exert a range of effects on the dynamics of the evolutionary process. A particularly marked effect comes from population structure, which can affect the probability that new mutations reach fixation. Our interest is in population structures, such as those depicted by ‘star graphs’, that amplify the effects of selection by further increasing the fixation probability of advantageous mutants and decreasing the fixation probability of disadvantageous mutants. The fact that star graphs increase the fixation probability of beneficial mutations has lead to the conclusion that evolution proceeds more rapidly in star-structured populations, compared with mixed (unstructured) populations. Here, we show that the effects of population structure on the rate of evolution are more complex and subtle than previously recognized and draw attention to the importance of fixation time. By comparing population structures that amplify selection with other population structures, both analytically and numerically, we show that evolution can slow down substantially even in populations where selection is amplified.

The Case for Open Preprints in Biology

The Case for Open Preprints in Biology:
by Philippe Desjardins-Proulx, Ethan P. White, Joel J. Adamson, Karthik Ram, Timothée Poisot, Dominique Gravel

GATA simple sequence repeats function as enhancer blocker boundaries

GATA simple sequence repeats function as enhancer blocker boundaries:
GATA simple sequence repeats function as enhancer blocker boundaries

Nature Communications 4, 1844 (2013). doi:10.1038/ncomms2872

Authors: Ram P. Kumar, Jaya Krishnan, Narendra Pratap Singh, Lalji Singh & Rakesh K. Mishra

A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells [DEVELOPMENT AND STEM CELLS]

A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells [DEVELOPMENT AND STEM CELLS]: Erez Nitzan, Shlomo Krispin, Elise R. Pfaltzgraff, Avihu Klar, Patricia A. Labosky, and Chaya Kalcheim

Understanding when and how multipotent progenitors segregate into diverse fates is a key question during embryonic development. The neural crest (NC) is an exemplary model system with which to investigate the dynamics of progenitor cell specification, as it generates a multitude of derivatives. Based on ‘in ovo’ lineage analysis, we previously suggested an early fate restriction of premigratory trunk NC to generate neural versus melanogenic fates, yet the timing of fate segregation and the underlying mechanisms remained unknown. Analysis of progenitors expressing a Foxd3 reporter reveals that prospective melanoblasts downregulate Foxd3 and have already segregated from neural lineages before emigration. When this downregulation is prevented, late-emigrating avian precursors fail to upregulate the melanogenic markers Mitf and MC/1 and the guidance receptor Ednrb2, generating instead glial cells that express P0 and Fabp. In this context, Foxd3 lies downstream of Snail2 and Sox9, constituting a minimal network upstream of Mitf and Ednrb2 to link melanogenic specification with migration. Consistent with the gain-of-function data in avians, loss of Foxd3 function in mouse NC results in ectopic melanogenesis in the dorsal tube and sensory ganglia. Altogether, Foxd3 is part of a dynamically expressed gene network that is necessary and sufficient to regulate fate decisions in premigratory NC. Their timely downregulation in the dorsal neural tube is thus necessary for the switch between neural and melanocytic phases of NC development.

Spatially Dependent Dynamic MAPK Modulation by the Nde1-Lis1-Brap Complex Patterns Mammalian CNS

Spatially Dependent Dynamic MAPK Modulation by the Nde1-Lis1-Brap Complex Patterns Mammalian CNS: Alison A. Lanctot, Chian-Yu Peng, Ashley S. Pawlisz, Milan Joksimovic, Yuanyi Feng. Regulating cell proliferation and differentiation in CNS development requires both extraordinary complexity and precision. Neural progenitors receive graded overlapping signals from midline signal....

Twitter “Hate Map” of the U.S.

Twitter “Hate Map” of the U.S.:
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Are gene loops the cause of transcriptional noise?

Are gene loops the cause of transcriptional noise?: Daniel Hebenstreit.

• Many genes produce mRNA irregularly, resulting in infrequent transcription bursts.
• Transcriptional bursting is a major source of noise, but its cause is unknown.<....

[Report] Networks of bZIP Protein-Protein Interactions Diversified Over a Billion Years of Evolution

[Report] Networks of bZIP Protein-Protein Interactions Diversified Over a Billion Years of Evolution: A comparative study of a dimeric transcription factor family looks at the evolution of protein interactions.

Authors: Aaron W. Reinke, Jiyeon Baek, Orr Ashenberg, Amy E. Keating

The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements

The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements:
by Pierre-Étienne Jacques, Justin Jeyakani, Guillaume Bourque

Although emerging evidence suggests that transposable elements (TEs) have contributed novel regulatory elements to the human genome, their global impact on transcriptional networks remains largely uncharacterized. Here we show that TEs have contributed to the human genome nearly half of its active elements. Using DNase I hypersensitivity data sets from ENCODE in normal, embryonic, and cancer cells, we found that 44% of open chromatin regions were in TEs and that this proportion reached 63% for primate-specific regions. We also showed that distinct subfamilies of endogenous retroviruses (ERVs) contributed significantly more accessible regions than expected by chance, with up to 80% of their instances in open chromatin. Based on these results, we further characterized 2,150 TE subfamily–transcription factor pairs that were bound in vivo or enriched for specific binding motifs, and observed that TEs contributing to open chromatin had higher levels of sequence conservation. We also showed that thousands of ERV–derived sequences were activated in a cell type–specific manner, especially in embryonic and cancer cells, and we demonstrated that this activity was associated with cell type–specific expression of neighboring genes. Taken together, these results demonstrate that TEs, and in particular ERVs, have contributed hundreds of thousands of novel regulatory elements to the primate lineage and reshaped the human transcriptional landscape.

Interspecific Divergence of Transcription Networks along Lines of Genetic Variance in Drosophila: Dimensionality, Evolvability, and Constraint

Interspecific Divergence of Transcription Networks along Lines of Genetic Variance in Drosophila: Dimensionality, Evolvability, and Constraint:
Change in gene expression is a major facilitator of phenotypic evolution. Understanding the evolutionary potential of gene expression requires taking into account complex systems of regulatory networks, the structure of which could potentially bias evolutionary trajectories. We analyzed the evolutionary potential and divergence of multigene expression in three well-characterized signaling pathways in Drosophila, the mitogen-activated protein kinase (MapK), the Toll, and the insulin receptor/Foxo (InR/Foxo or InR/TOR) pathways in a multivariate quantitative genetic framework. Gene expression data from a natural population of D. melanogaster were used to estimate the genetic variance–covariance matrices (G) for each network. Although most genes within each pathway exhibited significant genetic variance, the number of independent dimensions of multivariate genetic variance was fewer than the number of genes analyzed. However, for expression, the reduction in dimensionality was not as large as seen for other trait types such as morphology. We then tested whether gene expression divergence between D. melanogaster and an additional six species of the Drosophila genus was biased along the major axes of standing variation observed in D. melanogaster. In many cases, divergence was restricted to directions of phenotypic space harboring above average levels of genetic variance in D. melanogaster, indicating that genetic covariances between genes within pathways have biased interspecific divergence. We tested whether co-expression of genes in both sexes has also biased the pattern of divergence. Including cross-sex genetic covariances increased the degree to which divergence was biased along major axes of genetic variance, suggesting that the co-expression of genes in males and females can generate further constraints on divergence across the Drosophila phylogeny. In contrast to patterns seen for morphological traits in vertebrates, transcriptional constraints do not appear to break down as divergence time between species increases, instead they persist over tens of millions of years of divergence.

Exaptation of Transposable Elements into Novel Cis-Regulatory Elements: Is the Evidence Always Strong?

Exaptation of Transposable Elements into Novel Cis-Regulatory Elements: Is the Evidence Always Strong?:

Transposable elements (TEs) are mobile genetic sequences that can jump around the genome from one location to another, behaving as genomic parasites. TEs have been particularly effective in colonizing mammalian genomes, and such heavy TE load is expected to have conditioned genome evolution. Indeed, studies conducted both at the gene and genome levels have uncovered TE insertions that seem to have been co-opted—or exapted—by providing transcription factor binding sites (TFBSs) that serve as promoters and enhancers, leading to the hypothesis that TE exaptation is a major factor in the evolution of gene regulation. Here, we critically review the evidence for exaptation of TE-derived sequences as TFBSs, promoters, enhancers, and silencers/insulators both at the gene and genome levels. We classify the functional impact attributed to TE insertions into four categories of increasing complexity and argue that so far very few studies have conclusively demonstrated exaptation of TEs as transcriptional regulatory regions. We also contend that many genome-wide studies dealing with TE exaptation in recent lineages of mammals are still inconclusive and that the hypothesis of rapid transcriptional regulatory rewiring mediated by TE mobilization must be taken with caution. Finally, we suggest experimental approaches that may help attributing higher-order functions to candidate exapted TEs.

Sperm, but Not Oocyte, DNA Methylome Is Inherited by Zebrafish Early Embryos

Sperm, but Not Oocyte, DNA Methylome Is Inherited by Zebrafish Early Embryos: Lan Jiang, Jing Zhang, Jing-Jing Wang, Lu Wang, Li Zhang, Guoqiang Li, Xiaodan Yang, Xin Ma, Xin Sun, Jun Cai, Jun Zhang, Xingxu Huang, Miao Yu, Xuegeng Wang, Feng Liu, Chung-I Wu, Chuan He, Bo Zhang, Weimin Ci, Jiang Liu. 5-methylcytosine is a major epigenetic modification that is sometimes called “the fifth nucleotide.” However, our knowledge of how offspring inherit the DNA methylome from parents is limited. We g....

Reprogramming the Maternal Zebrafish Genome after Fertilization to Match the Paternal Methylation Pattern

Reprogramming the Maternal Zebrafish Genome after Fertilization to Match the Paternal Methylation Pattern: Magdalena E. Potok, David A. Nix, Timothy J. Parnell, Bradley R. Cairns. Early vertebrate embryos must achieve totipotency and prepare for zygotic genome activation (ZGA). To understand this process, we determined the DNA methylation (DNAme) profiles of zebrafish gamet....

Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells

Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells:

Casey A. Gifford, Michael J. Ziller, Hongcang Gu, Cole Trapnell, Julie Donaghey, Alexander Tsankov, Alex K. Shalek, David R. Kelley, Alexander A. Shishkin, Robbyn Issner, Xiaolan Zhang, Michael Coyne, Jennifer L. Fostel, Laurie Holmes, Jim Meldrim, Mitchell Guttman, Charles Epstein, Hongkun Park, Oliver Kohlbacher, John Rinn, Andreas Gnirke, Eric S. Lander, Bradley E. Bernstein, Alexander Meissner. Differentiation of human embryonic stem cells (hESCs) provides a unique opportunity to study the regulatory mechanisms that facilitate cellular transitions in a human context. To that end, we perf....

Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells

Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells:

Wei Xie, Matthew D. Schultz, Ryan Lister, Zhonggang Hou, Nisha Rajagopal, Pradipta Ray, John W. Whitaker, Shulan Tian, R. David Hawkins, Danny Leung, Hongbo Yang, Tao Wang, Ah Young Lee, Scott A. Swanson, Jiuchun Zhang, Yun Zhu, Audrey Kim, Joseph R. Nery, Mark A. Urich, Samantha Kuan, Chia-an Yen, Sarit Klugman, Pengzhi Yu, Kran Suknuntha, Nicholas E. Propson, Huaming Chen, Lee E. Edsall, Ulrich Wagner, Yan Li, Zhen Ye, Ashwinikumar Kulkarni, Zhenyu Xuan, Wen-Yu Chung, Neil C. Chi, Jessica E. Antosiewicz-Bourget, Igor Slukvin, Ron Stewart, Michael Q. Zhang, Wei Wang, James A. Thomson, Joseph R. Ecker, Bing Ren. Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryoni....

Synthetic circuits integrating logic and memory in living cells

Synthetic circuits integrating logic and memory in living cells:
Nature Biotechnology 31, 448 (2013).
doi:10.1038/nbt.2510

Authors: Piro Siuti, John Yazbek & Timothy K Lu

Logic and memory are essential functions of circuits that generate complex, state-dependent responses. Here we describe a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy allowed us to create all 16 two-input Boolean logic functions in living Escherichia coli cells without requiring cascades comprising multiple logic gates. We demonstrate long-term maintenance of memory for at least 90 cell generations and the ability to interrogate the states of these synthetic devices with fluorescent reporters and PCR. Using this approach we created two-bit digital-to-analog converters, which should be useful in biotechnology applications for encoding multiple stable gene expression outputs using transient inputs of inducers. We envision that this integrated logic and memory system will enable the implementation of complex cellular state machines, behaviors and pathways for therapeutic, diagnostic and basic science applications.

Memory storage in mushroom body output neurons [Neuroscience]

Memory storage in mushroom body output neurons [Neuroscience]: Memory is initially labile and gradually consolidated over time through new protein synthesis into a long-lasting stable form. Studies of odor-shock associative learning in Drosophila have established the mushroom body (MB) as a key brain structure involved in olfactory long-term memory (LTM) formation. Exactly how early neural activity encoded in...

Regulatory network evolution [Evolution]

Regulatory network evolution [Evolution]: The genetic basis of bacterial adaptation to a natural environment has been investigated in a highly successful Pseudomonas aeruginosa lineage (DK2) that evolved within the airways of patients with cystic fibrosis (CF) for more than 35 y. During evolution in the CF airways, the DK2 lineage underwent substantial phenotypic changes,...

Wor3, a previously undescribed DNA-binding protein [Biochemistry]

Wor3, a previously undescribed DNA-binding protein [Biochemistry]: Sequence-specific DNA-binding proteins are among the most important classes of gene regulatory proteins, controlling changes in transcription that underlie many aspects of biology. In this work, we identify a transcriptional regulator from the human fungal pathogen Candida albicans that binds DNA specifically but has no detectable homology with any previously...

FACT action during chromatin transcription [Biochemistry]

FACT action during chromatin transcription [Biochemistry]: FACT (facilitates chromatin transcription) is a histone chaperone that promotes chromatin recovery during transcription, with additional roles in cell differentiation. Although several models of the action of FACT during transcription have been proposed, they remain to be experimentally evaluated. Here we show that human FACT (hFACT) facilitates transcription through chromatin...

Single-molecule epigenomics [Applied Physical Sciences]

Single-molecule epigenomics [Applied Physical Sciences]: Proper placement of epigenetic marks on DNA and histones is fundamental to normal development, and perturbations contribute to a variety of disease states. Combinations of marks act together to control gene expression; therefore, detecting their colocalization is important, but because of technical challenges, such measurements are rarely reported. Instead, measurements...

Clustering of locally adaptive loci in the genome [Evolution]

Clustering of locally adaptive loci in the genome [Evolution]: Numerous studies of ecological genetics have found that alleles contributing to local adaptation sometimes cluster together, forming “genomic islands of divergence.” Divergence hitchhiking theory posits that these clusters evolve by the preferential establishment of tightly linked locally adapted mutations, because such linkage reduces the rate that recombination breaks up locally...

Dynamic binding of RBPJ is determined by Notch signaling status [Research Papers]

Dynamic binding of RBPJ is determined by Notch signaling status [Research Papers]:

Notch signaling plays crucial roles in mediating cell fate choices in all metazoans largely by specifying the transcriptional output of one cell in response to a neighboring cell. The DNA-binding protein RBPJ is the principle effector of this pathway in mammals and, together with the transcription factor moiety of Notch (NICD), regulates the expression of target genes. The prevalent view presumes that RBPJ statically occupies consensus binding sites while exchanging repressors for activators in response to NICD. We present the first specific RBPJ chromatin immunoprecipitation and high-throughput sequencing study in mammalian cells. To dissect the mode of transcriptional regulation by RBPJ and identify its direct targets, whole-genome binding profiles were generated for RBPJ; its coactivator, p300; NICD; and the histone H3 modifications H3 Lys 4 trimethylation (H3K4me3), H3 Lys 4 monomethylation (H3K4me1), and histone H3 Lys 27 acetylation (H3K27ac) in myogenic cells under active or inhibitory Notch signaling conditions. Our results demonstrate dynamic binding of RBPJ in response to Notch activation at essentially all sites co-occupied by NICD. Additionally, we identify a distinct set of sites where RBPJ recruits neither NICD nor p300 and binds DNA statically, irrespective of Notch activity. These findings significantly modify our views on how RBPJ and Notch signaling mediate their activities and consequently impact on cell fate decisions.

What Happens During 1 Second of HFT?

What Happens During 1 Second of HFT?:
1/2 second of trading activity in Johnson & Johnson (symbol JNJ) on May 2, 2013


Published on May 3, 2013
Nanex explains:

“The bottom box (SIP) shows the National Best Bid and Offer. Watch how much it changes in the blink of an eye.
Watch High Frequency Traders (HFT) at the millisecond level jam thousands of quotes in the stock of Johnson and Johnson (JNJ) through our financial networks on May 2, 2013. Video shows 1/2 second of time. If any of the connections are not running perfectly, High Frequency Traders can profit from the price discrepancies that result. There is no economic justification for this abusive behavior.
Each box represents one exchange. The SIP (CQS in this case) is the box at 6 o’clock. It shows the National Best Bid/Offer. Watch how much it changes in a fraction of a second. The shapes represent quote changes which are the result of a change to the top of the book at each exchange. The time at the bottom of the screen is Eastern Time HH:MM:SS:mmm (mmm = millisecond). We slow time down so you can see what goes on at the millisecond level. A millisecond (ms) is 1/1000th of a second.
Note how every exchange must process every quote from the others — for proper trade through price protection. This complex web of technology must run flawlessly every millisecond of the trading day, or arbitrage (HFT profit) opportunities will appear. It is easy for HFTs to cause delays in one or more of the connections between each exchange.”

Source: Nanex

How Did Feathers Evolve?

How Did Feathers Evolve?:
To look at the evolution of modern bird feathers, we must start a long time ago, with the dinosaurs from whence they came. We see early incarnations of feathers on dinosaur fossils, and remnants of dinosaurs in a bird’s wish bone. Carl Zimmer explores the stages of evolution and how even the reasons for feathers have evolved over millions of years.


Lesson by Carl Zimmer, animation by Armella Leung.
For more, see Ed Ted