Pesquisa descobre que dano potencial ao DNA pela técnica CRISPR-Cas9 tem sido seriamente subestimada!!!

terça-feira, julho 17, 2018

Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements 

Michael Kosicki, Kärt Tomberg & Allan Bradley

CRISPR–Cas9 is poised to become the gene editing tool of choice in clinical contexts. Thus far, exploration of Cas9-induced genetic alterations has been limited to the immediate vicinity of the target site and distal off-target sequences, leading to the conclusion that CRISPR–Cas9 was reasonably specific. Here we report significant on-target mutagenesis, such as large deletions and more complex genomic rearrangements at the targeted sites in mouse embryonic stem cells, mouse hematopoietic progenitors and a human differentiated cell line. Using long-read sequencing and long-range PCR genotyping, we show that DNA breaks introduced by single-guide RNA/Cas9 frequently resolved into deletions extending over many kilobases. Furthermore, lesions distal to the cut site and crossover events were identified. The observed genomic damage in mitotically active cells caused by CRISPR–Cas9 editing may have pathogenic consequences.

FREE PDF GRATIS: Nature Biotechnology

Contra o teorema da seleção natural de Fisher: agora com mutações!

segunda-feira, julho 16, 2018

Journal of Mathematical Biology

June 2018, Volume 76, Issue 7, pp 1589–1622 | Cite as

The fundamental theorem of natural selection with mutations

Authors and affiliations

William F. Basener 1

John C. Sanford 2

1.Rochester Institute of Technology Rochester USA

2.Horticulture Section NYSAES Geneva USA

Open AccessArticle

First Online: 07 November 2017


The mutation–selection process is the most fundamental mechanism of evolution. In 1935, R. A. Fisher proved his fundamental theorem of natural selection, providing a model in which the rate of change of mean fitness is equal to the genetic variance of a species. Fisher did not include mutations in his model, but believed that mutations would provide a continual supply of variance resulting in perpetual increase in mean fitness, thus providing a foundation for neo-Darwinian theory. In this paper we re-examine Fisher’s Theorem, showing that because it disregards mutations, and because it is invalid beyond one instant in time, it has limited biological relevance. We build a differential equations model from Fisher’s first principles with mutations added, and prove a revised theorem showing the rate of change in mean fitness is equal to genetic variance plus a mutational effects term. We refer to our revised theorem as the fundamental theorem of natural selection with mutations. Our expanded theorem, and our associated analyses (analytic computation, numerical simulation, and visualization), provide a clearer understanding of the mutation–selection process, and allow application of biologically realistic parameters such as mutational effects. The expanded theorem has biological implications significantly different from what Fisher had envisioned.


Population genetics Population dynamics Mutations Fitness Fisher Fundamental theorem of natural selection Natural selection Mutational meltdown

Viés em ciência e comunicação - um manual de campo

Bias in Science and Communication - A field guide

Matthew Welsh
Australian School of Petroleum,
University of Adelaide, Adelaide, Australia


This book is intended as an introduction to a wide variety of biases affecting human cognition, with a specific focus on how they affect scientists and the communication of science. A significant point, however, should be made up front: scientists are people and the biases that are discussed herein are, for the most part, generic in that they affect people in general rather than being specific to any particular group of people. That is, the decision making biases of experts and specialists tend to be more similar to those of lay-people than different (although chapter 10 will discuss situations where that is not the case). The role of this book, therefore, is to lay out how these common biases affect the specific types of judgements, decisions and communications made by scientists.

The book is divided into four parts. The first (chapters 1–3), introduces the reader to a variety of decision biases, the field of decision making in general and fundamental considerations regarding the psychology underlying different types of communication.

Each chapter in the second part of the book (chapters 4–10) will focus on a specific bias or a set of related decision making tendencies, describing the general effect, how they impact decisions and some of the implications for scientists’ decisions and communications.

Part 3 (chapters 11–13) brings insights about these individual biases together to demonstrate how they can combine and interact to produce a variety of welldocumented effects, including publication bias and stubborn denial of what, to scientists, are regarded as accepted facts. It also covers, more broadly, the ways in which biases can be overcome or avoided.

Finally, part 4 (chapter 14) draws overall conclusions about the impact of biases on science and communication, with advice on how best to move forward given what we know about their modes of action and amelioration strategies.

In all cases, an effort has been made to ensure that the latest information is incorporated and, where there are disputes or disagreements over the causes or nature of biases, alternative views are noted for those interested in following up in greater detail.

Each chapter also includes advice or exercises to help readers to identify or reduce biases in their own thinking.

@ IOP Publishing Ltd 2018

FREE DOWNLOAD GRATIS: IOPScience - Institute of Physics

Ontologia, causalidade e metodologia em programas de pesquisas evolucionárias

domingo, julho 15, 2018

Ontology, Causality, and Methodology of Evolutionary Research Programs

Otsuka, Jun (2018)

Source/Fonte: University of Arkansas


Scientific conflicts often stem from differences in the conceptual framework through which scientists view and understand their own field. In this chapter, I analyze the ontological and methodological assumptions of three traditions in evolutionary biology, namely, Ernst Mayr’s population thinking, the gene-centered view of the Modern Syn thesis (MS), and the Extended Evolutionary Synthesis (EES). Each of these frameworks presupposes a different account of "evolutionary causes," and this discrepancy prevents mutual understanding and objective evaluation in the recent contention surrounding the EES. From this perspective, the chapter characterizes the EES research program as an attempt to introduce causal structures beyond genes as additional units of evolution, and compares its research methodology and objectives with those of the traditional MS framework.


Novas espécies podem surgir de rápida evolução mitocondrial???

sexta-feira, julho 13, 2018

Genomic signatures of mitonuclear coevolution across populations of Tigriopus californicus

Felipe S. Barreto, Eric T. Watson, Thiago G. Lima, Christopher S. Willett, Suzanne Edmands, Weizhong Li & Ronald S. Burton 

Nature Ecology & Evolution (2018)

Assembly and evolution of a copepod genome.


The copepod Tigriopus californicus shows extensive population divergence and is becoming a model for understanding allopatric differentiation and the early stages of speciation. Here, we report a high-quality reference genome for one population (~190 megabases across 12 scaffolds, and ~15,500 protein-coding genes). Comparison with other arthropods reveals 2,526 genes presumed to be specific to T. californicus, with an apparent proliferation of genes involved in ion transport and receptor activity. Beyond the reference population, we report re-sequenced genomes of seven additional populations, spanning the continuum of reproductive isolation. Populations show extreme mitochondrial DNA divergence, with higher levels of amino acid differentiation than observed in other taxa. Across the nuclear genome, we find elevated protein evolutionary rates and positive selection in genes predicted to interact with mitochondrial DNA and the proteins and RNA it encodes in multiple pathways. Together, these results support the hypothesis that rapid mitochondrial evolution drives compensatory nuclear evolution within isolated populations, thereby providing a potentially important mechanism for causing intrinsic reproductive isolation.


This work was supported by US National Science Foundation grants (IOS1154321 to S.E.; IOS1155030 to R.S.B.; and IOS1155325 to C.S.W.) and Oregon State University faculty startup funds to F.S.B. The authors thank S. Morgan and R. J. Pereira for help with sample collection.

Author information


Department of Integrative Biology, Oregon State University, Corvallis, OR, USA

Felipe S. Barreto

Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA

Felipe S. Barreto, Thiago G. Lima & Ronald S. Burton

Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA

Eric T. Watson & Suzanne Edmands

Department of Biology, University of North Carolina, Chapel Hill, NC, USA

Thiago G. Lima & Christopher S. Willett

Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA, USA

Weizhong Li


F.S.B., E.T.W., T.G.L., C.S.W., S.E. and R.S.B. contributed to the design of the project, collection of biological samples, and sequence data acquisition. W.L. contributed to initial genome sequence assembly. F.S.B., E.T.W. and C.S.W. contributed to genome annotation. F.S.B., E.T.W., T.G.L. and C.S.W. contributed to computational and statistical analyses. F.S.B., E.T.W., T.G.L., C.S.W., S.E. and R.S.B. contributed to data interpretation and writing of the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Felipe S. Barreto.

A espécie humana não procede de uma única população ancestral de uma região da África

Did Our Species Evolve in Subdivided Populations across Africa, and Why Does It Matter?

Eleanor M.L. Scerri'Correspondence information about the author Eleanor M.L. ScerriEmail the author Eleanor M.L. Scerri, Mark G. Thomas, Andrea Manica, Philipp Gunz, Jay T. Stock, Chris Stringer, Matt Grove, Huw S. Groucutt, Axel Timmermann, G. Philip Rightmire, Francesco d’Errico, Christian A. Tryon, Nick A. Drake, Alison S. Brooks, Robin W. Dennell, Richard Durbin, Brenna M. Henn, Julia Lee-Thorp, Peter deMenocal, Michael D. Petraglia, Jessica C. Thompson, Aylwyn Scally, Lounès Chikhi

Published Online: July 11, 2018

Publication stage: In Press Corrected Proof

Open access funded by World Health Organization

Source/Fonte: Nature


The view that Homo sapiens evolved from a single region/population within Africa has been given primacy in studies of human evolution.

However, developments across multiple fields show that relevant data are no longer consistent with this view

We argue instead that Homo sapiens evolved within a set of interlinked groups living across Africa, whose connectivity changed through time.

Genetic models therefore need to incorporate a more complex view of ancient migration and divergence in Africa.

We summarize this new framework emphasizing population structure, outline how this changes our understanding of human evolution, and identify new research directions.

We challenge the view that our species, Homo sapiens, evolved within a single population and/or region of Africa. The chronology and physical diversity of Pleistocene human fossils suggest that morphologically varied populations pertaining to the H. sapiens clade lived throughout Africa. Similarly, the African archaeological record demonstrates the polycentric origin and persistence of regionally distinct Pleistocene material culture in a variety of paleoecological settings. Genetic studies also indicate that present-day population structure within Africa extends to deep times, paralleling a paleoenvironmental record of shifting and fractured habitable zones. We argue that these fields support an emerging view of a highly structured African prehistory that should be considered in human evolutionary inferences, prompting new interpretations, questions, and interdisciplinary research directions.

A Different View of African Origins

The lineage of Homo sapiens probably originated in Africa at least ∼500 thousand years ago (ka) [1], and the earliest observed morphological manifestations of this clade appeared by ∼300 ka [2]. Early H. sapiens fossils do not demonstrate a simple linear progression towards contemporary human morphology. Instead, putative early H. sapiens remains exhibit remarkable morphological diversity and geographical spread. Together with recent archaeological and genetic lines of evidence, these data are consistent with the view that our species originated and diversified within strongly subdivided (i.e., structured) populations, probably living across Africa, that were connected by sporadic gene flow [1, 3, 4, 5, 6, 7, 8]. This concept of ‘African multiregionalism’ [1] may also include hybridization between H. sapiens and more divergent hominins (see Glossary) living in different regions [1, 9, 10, 11, 12]. Crucially, such population subdivisions may have been shaped and sustained by shifts in ecological boundaries [7, 13, 14], challenging the view that our species was endemic to a single region or habitat, and implying an often underacknowledged complexity to our African origins.

In this paper we examine and synthesize fossil, archaeological, genetic, and paleoenvironmental data to refine our understanding of the time-depth, character, and maintenance of Pleistocene population structure. In doing so, we attempt to separate data from inference to stress that using models of population structure fundamentally changes interpretations of recent human evolution.

The Morphological Diversity and Spread of the Homo sapiens Clade

The constellation of morphological features characterizing H. sapiens is debated. This has strongly impacted on interpretations of recent human origins by variably including or excluding different fossils from interpretative analyses. For example, different morphological criteria and analytical methods have been used to support both a gradual, mosaic-like process of modernization of our species or, conversely, a punctuated speciation (e.g., [1]).

Extant human crania are characterized by a combination of features that distinguish us from our fossil relatives and ancestors, such as a small and gracile face, a chin, and a globular braincase. However, these typical modern human features emerge in a mosaic-like fashion within the H. sapiens clade. The oldest currently recognized members of the H. sapiens clade, from Jebel Irhoud in North Africa, have a facial morphology very similar to extant H. sapiens, as well as endocranial volumes that fall within the contemporary range of variation [2]. However, their braincase shapes are elongated rather than globular, suggesting that distinctive features of brain shape, and possibly brain function, evolved within H. sapiens [2, 5] (Figure 1). Other early H. sapiens fossils from Florisbad in South Africa (∼260 ka), Omo Kibish (∼195 ka) and Herto (∼160 ka), both in Ethiopia, are morphologically diverse [1, 16]. This diversity has led some researchers to propose that fossils such as Jebel Irhoud and Florisbad actually represent a more primitive species called ‘H. helmei’, using the binomen given to the Florisbad partial cranium in 1935 [17, 18]. In a similar vein, the fossil crania from Herto [19], which combine a relatively globular braincase with a robust occipital and large face, were described as the subspecies H. sapiens idaltu because they fall outside the variation of recent humans.

However, we view H. sapiens as an evolving lineage with deep African roots, and therefore prefer to recognize such fossils as part of the diversity shown by early members of the H. sapiens clade. The full suite of cranial features characterizing contemporary humans does not appear until fairly recently, between about ∼100–40 ka [20]. The character and chronology of early H. sapiens fossils, together with their geographic distribution across Africa, suggests that evolution may at times have progressed independently in different regions, in populations that were often semi-isolated for millennia by distance and/or ecological barriers, such as hyperarid regions or tropical forests.

Further insights into the geographic extent and potential habitat diversity of early H. sapiens populations can be gained from more recent forager populations in Africa, which were also strongly structured. For example, Later Stone Age (LSA) human remains highlight both the retention of ‘archaic’ traits and the maintenance of considerable morphological diversity into the terminal Pleistocene [11, 21]. In the Holocene, the skeletal record becomes much richer, but there remains considerable spatial variation in morphology. Variation between populations in different regions and environments of Africa may have been shaped by isolation-by-distance and local environmental adaptations [22, 23, 24, 25, 26]. For example, challenging environments (e.g., deserts, rainforest) and isolation have likely played a significant role in shaping the population structure of Holocene African foragers and isolated hunter-gatherers across the tropics [25, 27].

Ultimately, the processes underlying the emergence of any ‘package’ of derived features diagnostic of early H. sapiens anatomy remain incompletely understood. However, the data do not seem to be consistent with the long-held view that human ancestry is derived predominantly from a single African region hosting a panmictic population. Instead, H. sapiens likely descended from a shifting structured population (i.e., a set of interlinked groups whose connectivity changed through time), each exhibiting different characteristics of anatomical ‘modernity’. The discovery that the primitive-looking H. naledi dates to between ∼335 ka and 236 ka [28], and that the Broken Hill 1 Homo heidelbergensis skull may date to ∼300–125 ka [29], also shows that other hominin species in Africa coexisted with H. sapiens, raising the possibility of African archaic interbreeding. Future research should attempt to determine which features evolved before the appearance of our species and which primarily developed within the evolutionary history of our species. Another key area concerns understanding the extent to which different processes shaped observed changes. For example, the narrowing of the pelvis may reflect different processes including neutral genetic drift, adaptation to ecological variation, and life-history variation.

Darwin, a coisa está ficando preta para sua teoria - cada pessoa tem anatomia cerebral única: mero acaso, fortuita necessidade ou design inteligente???

terça-feira, julho 10, 2018

Identification of individual subjects on the basis of their brain anatomical features

Seyed Abolfazl Valizadeh, Franziskus Liem, Susan Mérillat, Jürgen Hänggi & Lutz Jäncke 

Scientific Reports volume 8, Article number: 5611 (2018) 

Three brain scans (from the front, side and above) of two different brains (pictured on the left and on the right) belonging to twins. The furrows and ridges are different in each person.
Credit: Lutz Jaencke, UZH


We examined whether it is possible to identify individual subjects on the basis of brain anatomical features. For this, we analyzed a dataset comprising 191 subjects who were scanned three times over a period of two years. Based on FreeSurfer routines, we generated three datasets covering 148 anatomical regions (cortical thickness, area, volume). These three datasets were also combined to a dataset containing all of these three measures. In addition, we used a dataset comprising 11 composite anatomical measures for which we used larger brain regions (11LBR). These datasets were subjected to a linear discriminant analysis (LDA) and a weighted K-nearest neighbors approach (WKNN) to identify single subjects. For this, we randomly chose a data subset (training set) with which we calculated the individual identification. The obtained results were applied to the remaining sample (test data). In general, we obtained excellent identification results (reasonably good results were obtained for 11LBR using WKNN). Using different data manipulation techniques (adding white Gaussian noise to the test data and changing sample sizes) still revealed very good identification results, particularly for the LDA technique. Interestingly, using the small 11LBR dataset also revealed very good results indicating that the human brain is highly individual.


The current analysis incorporates data from the Longitudinal Healthy Aging Brain (LHAB) database project, which is carried out as one of the core projects at the International Normal Aging and Plasticity Imaging Center/INAPIC and the University Research Priority Program “Dynamics of Healthy Aging” of the University of Zurich. This work was supported by the Velux Stiftung (project No. 369), by the University Research Priority Program “Dynamics of Healthy Aging” of the University of Zurich. We would also like to thank professor Carolin Strobl (Department of Psychology, University of Zurich) and professor Robert Riener (Department of Health Sciences and Technology, ETH Zurich) for their contribution to this paper. All subjects gave written informed consent prior to participating in the study. In addition, all methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by the ethical committee of the canton of Zurich (KEK-ZH-Nr. 2010–0267).

Author information


Division Neuropsychology, Department of Psychology, University of Zurich, Zurich, Switzerland

Seyed Abolfazl Valizadeh, Jürgen Hänggi & Lutz Jäncke

Sensory-Motor Systems Lab, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland

Seyed Abolfazl Valizadeh

International Normal Aging and Plasticity Imaging Center (INAPIC), University of Zurich, Zurich, Switzerland

Susan Mérillat & Lutz Jäncke

University Research Priority Program (URPP) “Dynamics of Healthy Aging”, University of Zurich, Zurich, Switzerland

Franziskus Liem, Susan Mérillat & Lutz Jäncke


S.V. wrote the Matlab code, conducted the analyses, interpreted the data, prepared figures, and wrote the main manuscript; L.J. participated in data analysis, design of the study, interpretation, and writing of the manuscript; F.L. S.M., J.H. participated in interpretation and writing of the manuscript.

Competing Interests

The authors declare no competing interests.

Corresponding author

Correspondence to Lutz Jäncke.

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About this article

Publication history

Received 13 November 2017 Accepted 14 March 2018

Published 04 April 2018

FREE PDF GRATIS: Scientific Reports Sup. Info.

O problema com as "teorias de multiversos": elas simplesmente não são científicas!!!

The problem with “multiverse theories”: they’re just not science

This admittedly catchy idea is undermining the integrity of physics

by Jim Baggott / June 25, 2018 /

Over the last few decades “multiverse theories” have become increasingly fashionable within a relatively small—but publicly vocal—group of theoretical physicists. This group specialises in foundational problems in cosmology, particle physics, and quantum mechanics. These theories are advertised as science’s answer to much that we can’t otherwise explain about the universe we inhabit, the elementary particles we have discovered in it, and the reasons for our own existence.

It’s “theories” plural because the multiverse is used in various ways to fill gaps in our current understanding. Cosmological multiverse theories “explain” why the initial conditions that prevailed at the Big Bang origin of our universe, and the physical constants and laws which shaped its subsequent evolution, appear so exquisitely fine-tuned to allow for the possibility of life. The idea is that there’s nothing particularly special about our “Goldilocks” universe: it is simply one of a (possibly infinite) number of universes, all with different initial conditions, constants, and laws. Most will be inhospitable, but it should come as no surprise to find ourselves in a universe which isn’t.


Read more here: Prospect Magazine

Darwin, mais design inteligente, mano: sistema de encriptação descoberto em genes!!!

segunda-feira, julho 09, 2018

Transient N-6-Methyladenosine Transcriptome Sequencing Reveals a Regulatory Role of m6A in Splicing Efficiency

Annita Louloupi5, Evgenia Ntini5, Thomas Conrad, Ulf Andersson Vang Ørom6

5These authors contributed equally

6Lead Contact

Article Info

Publication History

Published: June 19, 2018 Accepted: May 23, 2018

Received in revised form: April 30, 2018 Received: January 10, 2018

User License

Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)

Source/Fonte: TeskaLabs


•A time-resolved high-resolution picture of m6A on nascent RNA transcripts

•m6A is deposited at nascent RNA and in introns

•m6A deposition at splice-junctions increases splicing kinetics

•High m6A levels in introns is associated with slow and alternative splicing


Splicing efficiency varies among transcripts, and tight control of splicing kinetics is crucial for coordinated gene expression. N-6-methyladenosine (m6A) is the most abundant RNA modification and is involved in regulation of RNA biogenesis and function. The impact of m6A on regulation of RNA splicing kinetics is unknown. Here, we provide a time-resolved high-resolution assessment of m6A on nascent RNA transcripts and unveil its importance for the control of RNA splicing kinetics. We find that early co-transcriptional m6A deposition near splice junctions promotes fast splicing, while m6A modifications in introns are associated with long, slowly processed introns and alternative splicing events. In conclusion, we show that early m6A deposition specifies the fate of transcripts regarding splicing kinetics and alternative splicing.

Ainda por explicar: quase um em cada cinco genes humanos ainda tem status de codificação não resolvido

Loose ends: almost one in five human genes still have unresolved coding status 

Federico Abascal David Juan Irwin Jungreis Laura Martinez Maria Rigau Jose Manuel Rodriguez Jesus Vazquez Michael L Tress

Nucleic Acids Research, gky587,

Published: 30 June 2018 

Article history Received: 15 May 2018 Revision Received: 12 June 2018

Accepted: 18 June 2018


Seventeen years after the sequencing of the human genome, the human proteome is still under revision. One in eight of the 22 210 coding genes listed by the Ensembl/GENCODE, RefSeq and UniProtKB reference databases are annotated differently across the three sets. We have carried out an in-depth investigation on the 2764 genes classified as coding by one or more sets of manual curators and not coding by others. Data from large-scale genetic variation analyses suggests that most are not under protein-like purifying selection and so are unlikely to code for functional proteins. A further 1470 genes annotated as coding in all three reference sets have characteristics that are typical of non-coding genes or pseudogenes. These potential non-coding genes also appear to be undergoing neutral evolution and have considerably less supporting transcript and protein evidence than other coding genes. We believe that the three reference databases currently overestimate the number of human coding genes by at least 2000, complicating and adding noise to large-scale biomedical experiments. Determining which potential non-coding genes do not code for proteins is a difficult but vitally important task since the human reference proteome is a fundamental pillar of most basic research and supports almost all large-scale biomedical projects.

Issue Section: Data Resources and Analyses

FREE PDF GRATIS: Nucleic Acids Research

Análise comparativa de alta resolução de genomas de grandes primatas

High-resolution comparative analysis of great ape genomes

Zev N. Kronenberg1, Ian T. Fiddes2,*, David Gordon1,3,*, Shwetha Murali1,3,*, Stuart Cantsilieris1,*, Olivia S. Meyerson4,*, Jason G. Underwood1,5,*, Bradley J. Nelson1,*, Mark J. P. Chaisson1,6, Max L. Dougherty1, Katherine M. Munson1, Alex R. Hastie7, Mark Diekhans2, Fereydoun Hormozdiari8, Nicola Lorusso9, Kendra Hoekzema1, Ruolan Qiu1, Karen Clark10, Archana Raja1,3, AnneMarie E. Welch1, Melanie Sorensen1, Carl Baker1, Robert S. Fulton11, Joel Armstrong2, Tina A. Graves-Lindsay11, Ahmet M. Denli12, Emma R. Hoppe1, PingHsun Hsieh1, Christopher M. Hill1, Andy Wing Chun Pang7, Joyce Lee7, Ernest T. Lam7, Susan K. Dutcher11, Fred H. Gage12, Wesley C. Warren11, Jay Shendure1,3, David Haussler2,13, Valerie A. Schneider10, Han Cao7, Mario Ventura9, Richard K. Wilson11, Benedict Paten2, Alex Pollen4,14, Evan E. Eichler1,3,†

See all authors and affiliations

Science 08 Jun 2018: Vol. 360, Issue 6393, eaar6343

A spotlight on great ape genomes

Most nonhuman primate genomes generated to date have been “humanized” owing to their many gaps and the reliance on guidance by the reference human genome. To remove this humanizing effect, Kronenberg et al. generated and assembled long-read genomes of a chimpanzee, an orangutan, and two humans and compared them with a previously generated gorilla genome. This analysis recognized genomic structural variation specific to humans and particular ape lineages. Comparisons between human and chimpanzee cerebral organoids showed down-regulation of the expression of specific genes in humans, relative to chimpanzees, related to noncoding variation identified in this analysis.

Science, this issue p. eaar6343

Structured Abstract


Understanding the genetic differences that make us human is a long-standing endeavor that requires the comprehensive discovery and comparison of all forms of genetic variation within great ape lineages.


The varied quality and completeness of ape genomes have limited comparative genetic analyses. To eliminate this contiguity and quality disparity, we generated human and nonhuman ape genome assemblies without the guidance of the human reference genome. These new genome assemblies enable both coarse and fine-scale comparative genomic studies.


We sequenced and assembled two human, one chimpanzee, and one orangutan genome using high-coverage (>65x) single-molecule, real-time (SMRT) long-read sequencing technology. We also sequenced more than 500,000 full-length complementary DNA samples from induced pluripotent stem cells to construct de novo gene models, increasing our knowledge of transcript diversity in each ape lineage. The new nonhuman ape genome assemblies improve gene annotation and genomic contiguity (by 30- to 500-fold), resulting in the identification of larger synteny blocks (by 22- to 74-fold) when compared to earlier assemblies. Including the latest gorilla genome, we now estimate that 83% of the ape genomes can be compared in a multiple sequence alignment.

We observe a modest increase in single-nucleotide variant divergence compared to previous genome analyses and estimate that 36% of human autosomal DNA is subject to incomplete lineage sorting. We fully resolve most common repeat differences, including full-length retrotransposons such as the African ape-specific endogenous retroviral element PtERV1. We show that the spread of this element independently in the gorilla and chimpanzee lineage likely resulted from a founder element that failed to segregate to the human lineage because of incomplete lineage sorting.

The improved sequence contiguity allowed a more systematic discovery of structural variation (>50 base pairs in length) (see the figure). We detected 614,186 ape deletions, insertions, and inversions, assigning each to specific ape lineages. Unbiased genome scaffolding (optical maps, bacterial artificial chromosome sequencing, and fluorescence in situ hybridization) led to the discovery of large, unknown complex inversions in gene-rich regions. Of the 17,789 fixed human-specific insertions and deletions, we focus on those of potential functional effect. We identify 90 that are predicted to disrupt genes and an additional 643 that likely affect regulatory regions, more than doubling the number of human-specific deletions that remove regulatory sequence in the human lineage. We investigate the association of structural variation with changes in human-chimpanzee brain gene expression using cerebral organoids as a proxy for expression differences. Genes associated with fixed structural variants (SVs) show a pattern of down-regulation in human radial glial neural progenitors, whereas human-specific duplications are associated with up-regulated genes in human radial glial and excitatory neurons (see the figure).


The improved ape genome assemblies provide the most comprehensive view to date of intermediate-size structural variation and highlight several dozen genes associated with structural variation and brain-expression differences between humans and chimpanzees. These new references will provide a stepping stone for the completion of great ape genomes at a quality commensurate with the human reference genome and, ultimately, an understanding of the genetic differences that make us human.


Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single– to mega–base pair–sized variants. We identified ~17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors.




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Distribuição desigual da variância mutacional em todo o transcriptoma da Drosophila serrata revelada pela análise de alta dimensionalidade da expressão gênica

Uneven Distribution of Mutational Variance Across the Transcriptome of Drosophila serrata Revealed by High-Dimensional Analysis of Gene Expression

Emma Hine, Daniel E. Runcie, Katrina McGuigan and Mark W. Blows

GENETICS Early online June 8, 2018;


There are essentially an infinite number of traits that could be measured on any organism, and almost all individual traits display genetic variation, yet substantial genetic variance in a large number of independent traits is not plausible under basic models of selection and mutation. One mechanism that may be invoked to explain the observed levels of genetic variance in individual traits is that pleiotropy results in fewer dimensions of phenotypic space with substantial genetic variance. Multivariate genetic analyses of small sets of functionally-related traits have shown that standing genetic variance is often concentrated in relatively few dimensions. It is unknown if a similar concentration of genetic variance occurs at a phenome-wide scale when many traits of disparate function are considered, or if the genetic variance generated by new mutations is also unevenly distributed across phenotypic space. Here, we used a Bayesian sparse factor model to characterize the distribution of mutational variance of 3385 gene expression traits of Drosophila serrata after 27 generations of mutation accumulation, and found that 46% of the estimated mutational variance was concentrated in just 21 dimensions with significant mutational heritability. We show that the extent of concentration of mutational variance into such a small subspace has the potential to substantially bias the response to selection of these traits.


Received May 10, 2018. Revision received May 10, 2018.

Accepted May 31, 2018.

Copyright © 2018, Genetics

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Entendendo o progresso da ciência

McCoy, C.D. (2018) Understanding the Progress of Science. [Preprint]


This paper develops a problem-solving account of scientific progress that takes understanding as the principal epistemic aim of science. It examines a recent paper of Bird's on scientific progress, argues for the primacy of understanding over knowledge in this context, illustrates the account using a Kuhnian picture of science, and defends it against knowledge reductionism.


Rastros ediacaranos tardios produzidos por animais bilatérios com apêndices pareados

Late Ediacaran trackways produced by bilaterian animals with paired appendages

Zhe Chen1,2,*, Xiang Chen1,3, Chuanming Zhou2,4, Xunlai Yuan1,2,3 and Shuhai Xiao5,*

1State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology, Chinese Academy of Sciences, Nanjing 210008, China.

2Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Nanjing 210008, China.

3University of Chinese Academy of Sciences, Beijing 100049, China.

4CAS Key Laboratory of Economic Stratigraphy and Palaeogeography, Nanjing Institute of Geology and Palaeontology, Chinese Academy of Sciences, Nanjing 210008, China.

5Department of Geosciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

↵*Corresponding author. Email: (S.X.); (Z.C.)

Science Advances 06 Jun 2018:

Vol. 4, no. 6, eaao6691

Trackways and burrows excavated in situ from the Shibantan Member.


Ediacaran trace fossils provide key paleontological evidence for the evolution of early animals and their behaviors. Thus far, however, this fossil record has been limited to simple surface trails and relatively shallow burrows. We report possible trackways, preserved in association with burrows, from the terminal Ediacaran Shibantan Member (ca. 551 to ca. 541 million years ago) in the Yangtze Gorges area of South China. These trace fossils represent the earliest known trackways. They consist of two rows of imprints arranged in poorly organized series or repeated groups. These trackways may have been produced by bilaterian animals with paired appendages, although the phylum-level phylogenetic affinity of the trace makers remains unknown. It is possible that the trackways and associated burrows were produced by the same trace maker, indicating a complex behavior involving both walking and burrowing. Together, these trackways and burrows mark the arrival of a new era characterized by an increasing geobiological footprint of bilaterian animals.

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Nova dinâmica inesperada para grandes moléculas de DNA em suspensão líquida

Topologically frustrated dynamics of crowded charged macromolecules in charged hydrogels

Di Jia & Murugappan Muthukumar 

Nature Communications volume 9, Article number: 2248 (2018) 

Fig. 1


Movement of charged macromolecules in crowded aqueous environments is a ubiquitous phenomenon vital to the various living processes and formulations of materials for health care. While study of diffusion of tracer amounts of probe macromolecules trapped inside concentrated solutions, gels, or random media has led to an enhanced understanding of this complex process, the collective dynamics of charged macromolecules embedded inside congested charge-bearing matrices still remains to be fully explored. Here we report a frustrated dynamics of DNA and synthetic polyelectrolytes inside a charged host hydrogel where the guest molecules do not diffuse. Instead, they exhibit a family of relaxation processes arising from a combination of conformational entropy and local chain dynamics, which are frustrated by the confinement from the gel. We also have developed a model explaining this new universality class of non-diffusive topologically frustrated dynamics of charged macromolecules.


We thank the National Science Foundation (DMR-1504265), AFOSR Grant FA9550-17-1-0160, and the National Institutes of Health (Grant No. R01HG002776-11) for financial support.

Author information


Department of Polymer Science and Engineering, University of Massachusetts, Amherst, MA, 01003, USA

Di Jia & Murugappan Muthukumar


M.M. conceived the project. D.J. designed the experiments, synthesized the gel, and performed all experiments. M.M. developed the theory. Both authors discussed and contributed to the interpretation of the data. The whole project was supervised by M.M.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Murugappan Muthukumar.