A evolução do mapa genótipo-fenótipo e o custo da pleiotropia em mamíferos

sábado, outubro 29, 2016

Evolution of the Genotype-to-Phenotype Map and the Cost of Pleiotropy in Mammals

Arthur Porto, Ryan Schmelter, John L. VandeBerg, Gabriel Marroig, James M. Cheverud

GENETICS Early online October 26, 2016; DOI: 10.1534/genetics.116.189431

Source/Fonte: Interface Focus


Evolutionary studies have long emphasized that the genetic architecture of traits holds important microevolutionary consequences. Yet, studies comparing the genetic architecture of traits across species are rare, and discussions of the evolution of genetic systems are made on theoretical arguments rather than on empirical evidence. Here, we compared the genetic architecture of cranial traits in two different mammalian model organisms, the gray short-tailed opossum, Monodelphis domestica, and the laboratory mouse, Mus musculus. We show that both organisms share a highly polygenic genetic architecture for craniofacial traits, with many loci of small effect. However, these two model species differ significantly in the overall degree of pleiotropy of the genotype-to-phenotype map, with opossums presenting a higher average degree of pleiotropy. They also diverge in their degree of genetic modularity, with opossums presenting less modular patterns of genetic association among traits. We argue that such differences highlight the context dependency of gene effects, with developmental systems shaping the variational properties of genetic systems. Finally, we also demonstrate based on the opossum data that current measurements for the relationship between the mutational effect size and the degree of pleiotropy need to be re-evaluated in relation to the importance of the cost of pleiotropy for mammals.


Received March 18, 2016. Accepted October 18, 2016.

Copyright © 2016, The Genetics Society of America 

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Al 'Apocalipse' Gore, por que a Terra experimenta uma era do gelo a cada 100.000 anos?

sexta-feira, outubro 28, 2016

Breathing more deeply: Deep ocean carbon storage during the mid-Pleistocene climate transition

Caroline H. Lear1, Katharina Billups2, Rosalind E.M. Rickaby3, Liselotte Diester-Haass4, Elaine M. Mawbey1 and Sindia M. Sosdian1

- Author Affiliations

1School of Earth and Ocean Sciences, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK
2School of Marine Science and Policy, University of Delaware, Lewes, Delaware 19716, USA
3Department of Earth Sciences, University of Oxford, South Parks Road, Oxford OX1 3AN, UK
4Universität des Saarlandes, Zentrum für Umweltforschung, 66041 Saarbrücken, Germany

Source/Fonte: The Hollywood Reporter


The ∼100 k.y. cyclicity of the late Pleistocene ice ages started during the mid-Pleistocene transition (MPT), as ice sheets became larger and persisted for longer. The climate system feedbacks responsible for introducing this nonlinear ice sheet response to orbital variations in insolation remain uncertain. Here we present benthic foraminiferal stable isotope (δ18O, δ13C) and trace metal records (Cd/Ca, B/Ca, U/Ca) from Deep Sea Drilling Project Site 607 in the North Atlantic. During the onset of the MPT, glacial-interglacial changes in δ13C values are associated with changes in nutrient content and carbonate saturation state, consistent with a change in water mass at our site from a nutrient-poor northern source during interglacial intervals to a nutrient-rich, corrosive southern source during glacial intervals. The respired carbon content of glacial Atlantic deep water increased across the MPT. Increased dominance of corrosive bottom waters during glacial intervals would have raised mean ocean alkalinity and lowered atmospheric pCO2. The amplitude of glacial-interglacial changes in δ13C increased across the MPT, but this was not mirrored by changes in nutrient content. We interpret this in terms of air-sea CO2 exchange effects, which changed the δ13C signature of dissolved inorganic carbon in the deep water mass source regions. Increased sea ice cover or ocean stratification during glacial times may have reduced CO2outgassing in the Southern Ocean, providing an additional mechanism for reducing glacial atmospheric pCO2. Conversely, following the establishment of the ∼100 k.y. glacial cycles, δ13C of interglacial northern-sourced waters increased, perhaps reflecting reduced invasion of CO2 into the North Atlantic following the MPT.
  • Received 13 July 2016.
  • Revision received 26 September 2016.
  • Accepted 28 September 2016.
Gold Open Access: This paper is published under the terms of the CC-BY license.

“Mapas vizinhos” revelam o formato 3D do genoma

Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization

Marco Di Stefano, Jonas Paulsen, Tonje G. Lien, Eivind Hovig & Cristian Micheletti

Scientific Reports 6, Article number: 35985 (2016)

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Biological physics Computational biophysics

Received: 06 June 2016 Accepted: 30 September 2016 Published online: 27 October 2016


Combining genome-wide structural models with phenomenological data is at the forefront of efforts to understand the organizational principles regulating the human genome. Here, we use chromosome-chromosome contact data as knowledge-based constraints for large-scale three-dimensional models of the human diploid genome. The resulting models remain minimally entangled and acquire several functional features that are observed in vivo and that were never used as input for the model. We find, for instance, that gene-rich, active regions are drawn towards the nuclear center, while gene poor and lamina associated domains are pushed to the periphery. These and other properties persist upon adding local contact constraints, suggesting their compatibility with non-local constraints for the genome organization. The results show that suitable combinations of data analysis and physical modelling can expose the unexpectedly rich functionally-related properties implicit in chromosome-chromosome contact data. Specific directions are suggested for further developments based on combining experimental data analysis and genomic structural modelling.

Additional Information

How to cite this article: Di Stefano, M. et al. Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization. Sci. Rep. 6, 35985; doi: 10.1038/srep35985 (2016).

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


We are grateful to Marc A. Marti-Renom, Davide Baù, and Angelo Rosa for useful discussions. This work was supported by The Norwegian Cancer Society [grant 71220-PR-2006-0433]; the Research Council of Norway; and the Italian Ministry of Education [grant PRIN 2010HXAW77].

Author information

Author notes

Marco Di Stefano & Jonas Paulsen

These authors contributed equally to this work.


SISSA, International School for Advanced Studies, Trieste, I-34136, Italy

Marco Di Stefano & Cristian Micheletti

Institute of Basic Medical Sciences, University of Oslo, Oslo, 0317, Norway

Jonas Paulsen

University of Oslo, Department of Mathematics, Oslo, 0316, Norway

Tonje G. Lien

Institute for Cancer Research, Oslo University Hospital, Department of Tumor Biology, Oslo, 0310, Norway

Eivind Hovig

University of Oslo, Department of Informatics, Oslo, 0316, Norway

Eivind Hovig

Institute of Cancer Genetics and Informatics, Oslo, 0310, Norway

Eivind Hovig


M.D.S., J.P., E.H. and C.M. conceived and designed the experiments; J.P. and T.G.L. performed statistical analyses; M.D.S. performed the molecular dynamics simulations; M.D.S. and J.P. analysed the data and implemented the analysis tools; M.D.S., J.P., E.H. and C.M. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Marco Di Stefano.

O motor flagelar bacteriano - pináculo da nanotecnologia: mero acaso, fortuita necessidade ou design inteligente?

A Delicate Nanoscale Motor Made by Nature—The Bacterial Flagellar Motor

Ruidong Xue1, Qi Ma1, Matthew A. B. Baker2,* andFan Bai1,*

Version of Record online: 25 JUN 2015

Advanced Science
Volume 2, Issue 9, September 2015

© 2015 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.


Keywords: molecular motor;bacterial flagellum; bacterial motility; chemotaxis; 


The bacterial flagellar motor (BFM) is a molecular complex ca. 45 nm in diameter that rotates the propeller that makes nearly all bacteria swim. The motor self-assembles out of ca. 20 different proteins and can not only rotate at up to 50 000 rpm, but can also switch rotational direction in milliseconds and navigate its environment to maneuver, on average, towards regions of greater benefit. The BFM is a pinnacle of evolution that informs and inspires the design of novel nanotechnology in the new era of synthetic biology.

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Notável preservação de tecidos cerebrais em um dinossauro iguanodonte do Cretáceo Inferior (145 a 100 milhões de anos)

quinta-feira, outubro 27, 2016

Remarkable preservation of brain tissues in an Early Cretaceous iguanodontian dinosaur

Martin D. Brasier1,†, David B. Norman2,*, Alexander G. Liu2,3,*, Laura J. Cotton4, Jamie E. H. Hiscocks5, Russell J. Garwood6,7, Jonathan B. Antcliffe8,9,10 and David Wacey3,11

- Author Affiliations

1Department of Earth Sciences, University of Oxford, South Parks Road, Oxford OX1 3AN, UK

2Department of Earth Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EQ, UK

3School of Earth Sciences, University of Bristol, Life Sciences Building, 24 Tyndall Avenue, Bristol BS8 1TQ, UK

4School of Biological Sciences, The University of Hong Kong, Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong SAR, China

5Cantelupe Road, Bexhill-on-Sea, East Sussex TN40 1PP, UK

6School of Earth and Environmental Sciences, University of Manchester, Manchester M13 9PL, UK

7Department of Earth Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK

8Institute of Earth Sciences, University of Lausanne, 1015 Lausanne, Switzerland

9Department of Zoology, University of Oxford, The Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK

10Oxford University Museum of Natural History, Parks Road, Oxford OX1 3PW, UK

11Centre for Microscopy Characterisation and Analysis, and Australian Research Council Centre of Excellence for Core to Crust Fluid Systems, The University of Western Australia, 35 Stirling Highway, Perth, WA 6009, Australia

- Author Notes

↵† Deceased 16 December 2014.

↵*Correspondence: agscl2@cam.ac.uk; dn102@cam.ac.uk


It has become accepted in recent years that the fossil record can preserve labile tissues. We report here the highly detailed mineralization of soft tissues associated with a naturally occurring brain endocast of an iguanodontian dinosaur found in c. 133 Ma fluvial sediments of the Wealden at Bexhill, Sussex, UK. Moulding of the braincase wall and the mineral replacement of the adjacent brain tissues by phosphates and carbonates allowed the direct examination of petrified brain tissues. Scanning electron microscopy (SEM) imaging and computed tomography (CT) scanning revealed preservation of the tough membranes (meninges) that enveloped and supported the brain proper. Collagen strands of the meningeal layers were preserved in collophane. The blood vessels, also preserved in collophane, were either lined by, or infilled with, microcrystalline siderite. The meninges were preserved in the hindbrain region and exhibit structural similarities with those of living archosaurs. Greater definition of the forebrain (cerebrum) than the hindbrain (cerebellar and medullary regions) is consistent with the anatomical and implied behavioural complexity previously described in iguanodontian-grade ornithopods. However, we caution that the observed proximity of probable cortical layers to the braincase walls probably resulted from the settling of brain tissues against the roof of the braincase after inversion of the skull during decay and burial.

Supplementary material: 

Information regarding associated fossil material, and additional images, can be found at https://doi.org/10.6084/m9.figshare.c.3519984

Gold Open Access: This article is published under the terms of the CC-BY 3.0 license.

© 2016 The Author(s). Published by The Geological Society of London


Geological Society, London, Special Publications Lyell Collection

Michael Behe: de perto e pessoal

Análise filogenômica de peixes Carangidae revela: a assimetria de peixes achatados surgiu em um piscar de olhos evolutivo

Phylogenomic analysis of carangimorph fishes reveals flatfish asymmetry arose in a blink of the evolutionary eye

Richard C. HarringtonEmail author, Brant C. Faircloth, Ron I. Eytan, W. Leo Smith, Thomas J. Near, Michael E. Alfaro and Matt Friedman

BMC Evolutionary Biology BMC series – open, inclusive and trusted 201616:224

DOI: 10.1186/s12862-016-0786-x © The Author(s). 2016

Received: 12 July 2016Accepted: 30 September 2016 Published: 21 October 2016



Flatfish cranial asymmetry represents one of the most remarkable morphological innovations among vertebrates, and has fueled vigorous debate on the manner and rate at which strikingly divergent phenotypes evolve. A surprising result of many recent molecular phylogenetic studies is the lack of support for flatfish monophyly, where increasingly larger DNA datasets of up to 23 loci have either yielded a weakly supported flatfish clade or indicated the group is polyphyletic. Lack of resolution for flatfish relationships has been attributed to analytical limitations for dealing with processes such as nucleotide non-stationarity and incomplete lineage sorting (ILS). We tackle this phylogenetic problem using a sequence dataset comprising more than 1,000 ultraconserved DNA element (UCE) loci covering 45 carangimorphs, the broader clade containing flatfishes and several other specialized lineages such as remoras, billfishes, and archerfishes.


We present a phylogeny based on UCE loci that unequivocally supports flatfish monophyly and a single origin of asymmetry. We document similar levels of discordance among UCE loci as in previous, smaller molecular datasets. However, relationships among flatfishes and carangimorphs recovered from multilocus concatenated and species tree analyses of our data are robust to the analytical framework applied and size of data matrix used. By integrating the UCE data with a rich fossil record, we find that the most distinctive carangimorph bodyplans arose rapidly during the Paleogene (66.0–23.03 Ma). Flatfish asymmetry, for example, likely evolved over an interval of no more than 2.97 million years.


The longstanding uncertainty in phylogenetic hypotheses for flatfishes and their carangimorph relatives highlights the limitations of smaller molecular datasets when applied to successive, rapid divergences. Here, we recovered significant support for flatfish monophyly and relationships among carangimorphs through analysis of over 1,000 UCE loci. The resulting time-calibrated phylogeny points to phenotypic divergence early within carangimorph history that broadly matches with the predictions of adaptive models of lineage diversification.

Keywords Adaptive radiation Carangimorpha Evolutionary innovation Pleuronectiformes UCE Ultraconserved elements

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Synthetic Biology: nova publicação científica promovendo a revolução biológico-cibernética

quarta-feira, outubro 26, 2016

Synthetic Biology: fostering the cyber-biological revolution

Jean Peccoud

First published online: 15 June 2016


Since the description, in 2000, of two artificial gene networks, synthetic biology has emerged as a new engineering discipline that catalyzes a change of culture in the life sciences. Recombinant DNA can now be fabricated rather than cloned. Instead of focusing on the development of ad-hoc assembly strategies, molecular biologists can outsource the fabrication of synthetic DNA molecules to a network of DNA foundries. Model-driven product development cycles that clearly identify design, build, and test phases are becoming as common in the life sciences as they have been in other engineering fields. A movement of citizen scientists with roots in community labs throughout the world is trying to democratize genetic engineering. It challenges the life science establishment just like visionaries in the 70s advocated that computing should be personal at a time when access to computers was mostly the privilege of government scientists. Synthetic biology is a cultural revolution that will have far reaching implications for the biotechnology industry. The work of synthetic biologists today prefigures a new generation of cyber-biological systems that may to lead to the 5th industrial revolution. By catering to the scientific publishing needs of all members of a diverse community, Synthetic Biology hopes to do its part to support the development of this new engineering discipline, catalyze the culture changes it calls for, and foster the development of a new industry far into the twenty first century.
On January 20, 2000, Nature published two articles reporting the design, fabrication, and characterization of two artificial gene networks. Timothy Gardner, Jim Collins, and Charles Cantor described a genetic toggle switch that could be flipped between an ON and OFF states using transient environmental signals [1]. Michael Elowitz and Stanislas Leibler described the Repressilator, a genetic circuit that exhibited oscillations of the expression of a reporter gene [2].
On the face of it, these two articles looked like biology papers. They included the description of new plasmids and reported data collected with instruments commonly used by biologists. And there was nothing particularly new in these experiments. Many molecular biologists had the skills necessary to assemble and characterize these plasmids but none of them thought of designing them. It took the minds of a mechanical engineer (T. Gardner) and a physicist (M. Elowitz) to imagine these circuits. The novelty of these articles was not so much in their biological aspect as it was in the applications of engineering principles to the design of circuits encoded in DNA molecules. These two articles have been a source of inspiration for many of us. They have catalyzed the emergence of a movement of dreamers aspiring to engineer DNA like their parents engineered silicon. This movement eventually led to the emergence of synthetic biology as a new field of engineering [3–5].
Fifteen years later, we have come to appreciate the culture change that synthetic biology calls for. We see many indications that this specialty has the potential to support an industrial revolution fueled by the emergence of cyber-biological systems across many segments of the economy. The dynamics between scientific breakthroughs and innovative industrial applications is well illustrated by the career paths of the discipline pioneers. Gardner left academia for industry 10 years ago to join one of the first synthetic biology startups while Elowitz stayed in academia where his work continues to deeply renew our understanding of biological processes.
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As proteínas "tampões" do flagelo bacteriano adotam diversos estados oligoméricos

terça-feira, outubro 25, 2016

Bacterial flagellar capping proteins adopt diverse oligomeric states

Sandra Postel Daniel Deredge Daniel A Bonsor Xiong Yu Kay Diederichs Saskia Helmsing Aviv Vromen Assaf Friedler Michael Hust Edward H Egelman Dorothy Beckett Patrick L Wintrode Eric J Sundberg 

University of Maryland School of Medicine, United States; University of Maryland School of Pharmacy, United States; University of Virginia, United States; University of Konstanz, Germany; Technische Universität Braunschweig, Germany; The Hebrew University of Jerusalem, Israel; University of Maryland College Park, United States

Published September 24, 2016

Cite as eLife 2016;5:e18857

Figure 2. Pseudomonas FliD forms hexamers in crystals.


Flagella are crucial for bacterial motility and pathogenesis. The flagellar capping protein (FliD) regulates filament assembly by chaperoning and sorting flagellin (FliC) proteins after they traverse the hollow filament and exit the growing flagellum tip. In the absence of FliD, flagella are not formed, resulting in impaired motility and infectivity. Here, we report the 2.2 Å resolution X-ray crystal structure of FliD from Pseudomonas aeruginosa, the first high-resolution structure of any FliD protein from any bacterium. Using this evidence in combination with a multitude of biophysical and functional analyses, we find that Pseudomonas FliD exhibits unexpected structural similarity to other flagellar proteins at the domain level, adopts a unique hexameric oligomeric state, and depends on flexible determinants for oligomerization. Considering that the flagellin filaments on which FliD oligomers are affixed vary in protofilament number between bacteria, our results suggest that FliD oligomer stoichiometries vary across bacteria to complement their filament assemblies.

eLife digest

Many bacteria, including several that cause diseases in people, have long whip-like appendages called flagella that extend well beyond their cell walls. Flagella can rotate and propel the bacteria through liquids, such as water or blood, and they are constructed primarily from thousands of copies of a single protein called flagellin. When flagella are built, the flagellin proteins are placed in their proper positions by another protein called FliD, several copies of which form a cap on the end of flagella. Without FliD, bacteria cannot properly assemble flagella and, thus, can no longer swim; this also hinders their ability to cause disease.

Determining the three-dimensional structure of a protein, down to the level of its individual atoms, can provide unique insights into how the protein operates. However, no one had resolved the structure of a FliD protein from any bacterium to this level of detail before.

Now, Postel et al. report the high-resolution structure of a large fragment of FliD from the bacterium Pseudomonas aeruginosa. The structure reveals that parts of this FliD protein are shaped like parts of other proteins from which flagella are constructed, including the flagellin protein that FliD places into position. Some parts of the FliD protein are also very flexible and these parts of the protein are responsible for holding numerous FliD proteins together as a cap. Finally, Postel et al. saw that six copies of FliD bind to one another to form a protein complex on the end of flagella. This last finding was particularly unexpected since it was thought that all FliD proteins formed five-membered cap complexes, an assumption that was based largely on studies of FliD from another bacterium called Salmonella.

The current structure covers about half of the FliD protein, and so the next challenge is to determine the structure of the full-length protein. An improved understanding of the structure of FliD may, in future, help researchers to design drugs that stop bacteria from building flagella and, therefore, from swimming and causing disease.


O universo está em expansão, pero no mucho!

Marginal evidence for cosmic acceleration from Type Ia supernovae

J. T. Nielsen, A. Guffanti & S. Sarkar

Scientific Reports 6, Article number: 35596 (2016)

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Received: 21 July 2016 Accepted: 03 October 2016 Published online: 21 October 2016

Source/Fonte: Planck Mission


The ‘standard’ model of cosmology is founded on the basis that the expansion rate of the universe is accelerating at present — as was inferred originally from the Hubble diagram of Type Ia supernovae. There exists now a much bigger database of supernovae so we can perform rigorous statistical tests to check whether these ‘standardisable candles’ indeed indicate cosmic acceleration. Taking account of the empirical procedure by which corrections are made to their absolute magnitudes to allow for the varying shape of the light curve and extinction by dust, we find, rather surprisingly, that the data are still quite consistent with a constant rate of expansion.


We thank the JLA collaboration for making their data and software public and M. Betoule for making the corrections we suggested to the catalogue. This work was supported by the Danish National Research Foundation through the Discovery Center at the Niels Bohr Institute and the award of a Niels Bohr Professorship to S.S.

Author information


Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, Copenhagen 2100, Denmark

J. T. Nielsen & S. Sarkar

Dipartimento di Fisica, Università degli Studi di Torino, via P. Giuria 1, I-10125 Torino, Italy

A. Guffanti

Rudolf Peierls Centre for Theoretical Physics, University of Oxford, 1 Keble Road, Oxford OX1 3NP, UK

S. Sarkar


All authors participated in the analysis and in the writing of the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to S. Sarkar.

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Duas espécies de dinossauros andaram da América do Sul à Austrália, via Antártida

New Australian sauropods shed light on Cretaceous dinosaur palaeobiogeography

Stephen F. Poropat, Philip D. Mannion, Paul Upchurch, Scott A. Hocknull, Benjamin P. Kear, Martin Kundrát, Travis R. Tischler, Trish Sloan, George H. K. Sinapius, Judy A. Elliott & David A. Elliott

Scientific Reports 6, Article number: 34467 (2016)

Download Citation

Biogeography Palaeontology Phylogenetics Taxonomy

Received: 15 April 2016 Accepted: 13 September 2016 Published online: 20 October 2016

Showing the possible high latitude dispersal routes that might have been utilised by titanosaurs and other sauropods during the late Albian–Turonian. The base map is the 105 Ma time slice from the Global Paleogeography and Tectonics in Deep Time series by Ron Blakey [© Colorado Plateau Geosystems Inc.]. 

Australian dinosaurs have played a rare but controversial role in the debate surrounding the effect of Gondwanan break-up on Cretaceous dinosaur distribution. Major spatiotemporal gaps in the Gondwanan Cretaceous fossil record, coupled with taxon incompleteness, have hindered research on this effect, especially in Australia. Here we report on two new sauropod specimens from the early Late Cretaceous of Queensland, Australia, that have important implications for Cretaceous dinosaur palaeobiogeography. Savannasaurus elliottorum gen. et sp. nov. comprises one of the most complete Cretaceous sauropod skeletons ever found in Australia, whereas a new specimen of Diamantinasaurus matildae includes the first ever cranial remains of an Australian sauropod. The results of a new phylogenetic analysis, in which both Savannasaurus and Diamantinasaurus are recovered within Titanosauria, were used as the basis for a quantitative palaeobiogeographical analysis of macronarian sauropods. Titanosaurs achieved a worldwide distribution by at least 125 million years ago, suggesting that mid-Cretaceous Australian sauropods represent remnants of clades which were widespread during the Early Cretaceous. These lineages would have entered Australasia via dispersal from South America, presumably across Antarctica. High latitude sauropod dispersal might have been facilitated by Albian–Turonian warming that lifted a palaeoclimatic dispersal barrier between Antarctica and South America.


We would like to thank the staff from the Australian Age of Dinosaurs Natural History Museum, the Queensland Museum, and the University of Queensland, and all of the volunteers, who participated in the “Elliot” and “Wade” digs from 2001–2005, and who prepared all of the specimens. We also thank the Elliott family for reinvigorating the search for dinosaurs in western Queensland, and for allowing excavations to take place on Belmont Station from 2001–2005. We are also grateful to all those who allowed us to study sauropod material in their care. S.F.P., S.A.H. and B.P.K.’s research was funded by an Australian Research Council Linkage Grant (LP100100339). P.D.M.’s research was supported by an Imperial College London Junior Research Fellowship. P.U.’s contribution was facilitated by a Leverhulme Trust Research Grant (RPG-129). M.K. was funded by the Swedish Research Council.

Author information

Author notes

Stephen F. Poropat, Philip D. Mannion & Paul Upchurch

These authors contributed equally to this work.


Department of Earth Sciences, Uppsala University, Uppsala, Sweden

Stephen F. Poropat & Benjamin P. Kear

Australian Age of Dinosaurs Museum of Natural History, The Jump-Up, Winton, Queensland, Australia

Stephen F. Poropat, Travis R. Tischler, Trish Sloan, George H. K. Sinapius, Judy A. Elliott & David A. Elliott

Department of Earth Science and Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom

Philip D. Mannion

Department of Earth Sciences, University College London, Gower Street, London WC1E 6BT, United Kingdom

Paul Upchurch

Geosciences, Queensland Museum, Hendra, Queensland, Australia

Scott A. Hocknull

Museum of Evolution, Uppsala University, Norbyvägen 16, SE-752 36 Uppsala, Sweden

Benjamin P. Kear

Department of Ecology, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, SK-84215, Bratislava, Slovak Republic

Martin Kundrát

Center for Interdisciplinary Biosciences, Faculty of Science, University of Pavol Jozef Šafárik, Jesenná 5, SK-04154, Košice, Slovak Republic

Martin Kundrát


S.F.P., P.D.M., P.U., S.A.H. and B.P.K. designed the project. S.A.H., T.S., G.H.K.S., J.A.E. and D.A.E. oversaw the collection, preparation and curation of the fossils. S.F.P., P.D.M. and P.U. described the specimens, and M.K. analysed the endocranial structure of AODF 836. S.F.P., P.D.M. and P.U. scored the specimens for the phylogenetic analysis, and P.D.M. ran the analysis. P.U. ran the quantitative palaeobiogeographic analysis. S.F.P., S.A.H., M.K. and T.R.T. assembled the figures. S.F.P., P.D.M. and P.U. wrote and prepared the Supplementary Information. All authors contributed to the writing of the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Stephen F. Poropat.

Todas as publicações científicas da Royal Society gratuitas até 6 de novembro de 2016

segunda-feira, outubro 24, 2016

Today marks the start of Open Access Week. All the Royal Society's journal content, including Notes and Records, will be free to access until Sunday 6 November. Please do pass this information on to all your relevant audiences. It is a once a year opportunity to access any article in our 350 year archive free of charge and without requiring a journal subscription. 

Análise matemática revela a arquitetura do genoma humano: mero acaso, fortuita necessidade ou design inteligente?

Dynamic Nucleosome Movement Provides Structural Information of Topological Chromatin Domains in Living Human Cells

Soya Shinkai , Tadasu Nozaki, Kazuhiro Maeshima, Yuichi Togashi


The mammalian genome is organized into submegabase-sized chromatin domains (CDs) including topologically associating domains, which have been identified using chromosome conformation capture-based methods. Single-nucleosome imaging in living mammalian cells has revealed subdiffusively dynamic nucleosome movement. It is unclear how single nucleosomes within CDs fluctuate and how the CD structure reflects the nucleosome movement. Here, we present a polymer model wherein CDs are characterized by fractal dimensions and the nucleosome fibers fluctuate in a viscoelastic medium with memory. We analytically show that the mean-squared displacement (MSD) of nucleosome fluctuations within CDs is subdiffusive. The diffusion coefficient and the subdiffusive exponent depend on the structural information of CDs. This analytical result enabled us to extract information from the single-nucleosome imaging data for HeLa cells. Our observation that the MSD is lower at the nuclear periphery region than the interior region indicates that CDs in the heterochromatin-rich nuclear periphery region are more compact than those in the euchromatin-rich interior region with respect to the fractal dimensions as well as the size. Finally, we evaluated that the average size of CDs is in the range of 100–500 nm and that the relaxation time of nucleosome movement within CDs is a few seconds. Our results provide physical and dynamic insights into the genome architecture in living cells.

Author Summary

The mammalian genome is partitioned into topological chromatin domains (CDs) in the living cell nuclei. Gene expression is highly regulated within CDs according to their structure, whereas chromatin itself is highly dynamic. This raises the following question: how is the CD structure in such dynamic chromatin? We developed a conceptual framework that unifies chromatin dynamics and structure. Using a polymer model with a fractal domain structure in a viscoelastic medium, we analytically show that nucleosome movement is subdiffusive and depends on CD structure. Hence, structural information can be extracted based on nucleosome movement in living cells with single-particle tracking experiments. This framework provides physical insights into the relationship between dynamic genome organization and gene expression.

Citation: Shinkai S, Nozaki T, Maeshima K, Togashi Y (2016) Dynamic Nucleosome Movement Provides Structural Information of Topological Chromatin Domains in Living Human Cells. PLoS Comput Biol 12(10): e1005136. doi:10.1371/journal.pcbi.1005136

Editor: Alexandre V. Morozov, Rutgers University, UNITED STATES

Received: July 12, 2016; Accepted: September 10, 2016; Published: October 20, 2016

Copyright: © 2016 Shinkai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: This research is supported by: Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Dynamic Approaches to Living System) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT; http://www.mext.go.jp/english/) and the Japan Agency for Medical Research and Development (AMED; http://www.amed.go.jp/en/); MEXT KAKENHI (JP16H01408 to SS, JP23115007 to YT, and JP23115005 to KM), and Research Fellowship for Young Scientists (JP13J04821 and JP16J07205) to TN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.