Células vivas "computam" usando circuitos gênicos: mero acaso, fortuita necessidade ou design inteligente???

quinta-feira, outubro 20, 2016

Synthetic mixed-signal computation in living cells

Jacob R. Rubens, Gianluca Selvaggio & Timothy K. Lu

Nature Communications 7, Article number: 11658 (2016)

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Biological techniques Computational biology and bioinformatics

Received: 04 September 2015 Accepted: 18 April 2016 Published online: 03 June 2016


Living cells implement complex computations on the continuous environmental signals that they encounter. These computations involve both analogue- and digital-like processing of signals to give rise to complex developmental programs, context-dependent behaviours and homeostatic activities. In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately. Here we integrate analogue and digital computation to implement complex hybrid synthetic genetic programs in living cells. We present a framework for building comparator gene circuits to digitize analogue inputs based on different thresholds. We then demonstrate that comparators can be predictably composed together to build band-pass filters, ternary logic systems and multi-level analogue-to-digital converters. In addition, we interface these analogue-to-digital circuits with other digital gene circuits to enable concentration-dependent logic. We expect that this hybrid computational paradigm will enable new industrial, diagnostic and therapeutic applications with engineered cells.


We would like to thank members of the Lu Lab, the MIT Microbiology Program and the MIT Synthetic Biology Center for their feedback. We thank the staff at the Koch Institute Flow Cytometry Core for their assistance in flow cytometry and Quintara Biosciences for DNA sequencing service. J.R.R. was supported by an NSF Graduate Research Fellowship. G.S. was supported by a ‘FCT, Fundação para a Ciência e a Tecnologia’ fellowship (#SFRH/BD/51576/2011). This work was supported by the National Science Foundation (#1350625 and #1124247), the Office of Naval Research (#N000141310424), an NIH New Innovator Award (#1DP2OD008435) and the NIH National Centers for Systems Biology (#1P50GM098792).

Author information


1Synthetic Biology Group, MIT Synthetic Biology Center, Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Jacob R. Rubens, Gianluca Selvaggio & Timothy K. Lu

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Jacob R. Rubens, Gianluca Selvaggio & Timothy K. Lu

Microbiology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Jacob R. Rubens & Timothy K. Lu

Computational and System Biology Group, Centre for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal

Gianluca Selvaggio

The Center for Microbiome Informatics and Therapeutics, Cambridge, Massachusetts 02139, USA

Timothy K. Lu


J.R.R. and T.K.L. conceived the study. J.R.R. and G.S. performed the experiments and collected the data. All authors analysed the data, discussed the results and wrote the manuscript.

Competing interests

J.R.R., G.S. and T.K.L. have filed a provisional patent application based on this work (‘Analogue to Digital Computations in Biological Systems’, PCT/US2015/067381).

Corresponding author

Correspondence to Timothy K. Lu.

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Darwin, pede pra sair: sua teoria não explica a origem e a evolução de um "simples" flagelo bacteriano!!!

quarta-feira, outubro 19, 2016

Sequenciamento profundo de 10.000 genomas humanos

Deep sequencing of 10,000 human genomes

Amalio Telenti a,b,1, Levi C. T. Pierce a,c,1, William H. Biggs a,1, Julia di Iulio a,b, Emily H. M. Wong a, Martin M. Fabani a, Ewen F. Kirkness a, Ahmed Moustafa a, Naisha Shah a, Chao Xie d, Suzanne C. Brewerton d, Nadeem Bulsara a, Chad Garner a, Gary Metzker a, Efren Sandoval a, Brad A. Perkins a, Franz J. Och a,c, Yaron Turpaz a,d, and J. Craig Venter a,b,2

Author Affiliations

a Human Longevity Inc., San Diego, CA 92121;

b J. Craig Venter Institute, La Jolla, CA 92037;

c Human Longevity Inc., Mountain View, CA 94041;

d Human Longevity Singapore Pte. Ltd., Singapore 138542

Contributed by J. Craig Venter, August 18, 2016 (sent for review July 1, 2016; reviewed by David B. Goldstein and Stephen W. Scherer)



Large-scale initiatives toward personalized medicine are driving a massive expansion in the number of human genomes being sequenced. Therefore, there is an urgent need to define quality standards for clinical use. This includes deep coverage and sequencing accuracy of an individual’s genome. Our work represents the largest effort to date in sequencing human genomes at deep coverage with these new standards. This study identifies over 150 million human variants, a majority of them rare and unknown. Moreover, these data identify sites in the genome that are highly intolerant to variation—possibly essential for life or health. We conclude that high-coverage genome sequencing provides accurate detail on human variation for discovery and clinical applications.


We report on the sequencing of 10,545 human genomes at 30×–40× coverage with an emphasis on quality metrics and novel variant and sequence discovery. We find that 84% of an individual human genome can be sequenced confidently. This high-confidence region includes 91.5% of exon sequence and 95.2% of known pathogenic variant positions. We present the distribution of over 150 million single-nucleotide variants in the coding and noncoding genome. Each newly sequenced genome contributes an average of 8,579 novel variants. In addition, each genome carries on average 0.7 Mb of sequence that is not found in the main build of the hg38 reference genome. The density of this catalog of variation allowed us to construct high-resolution profiles that define genomic sites that are highly intolerant of genetic variation. These results indicate that the data generated by deep genome sequencing is of the quality necessary for clinical use.

genomics noncoding genome human genetic diversity


1 A.T., L.C.T.P., and W.H.B. contributed equally to this work.

2 To whom correspondence should be addressed. Email: jcventer@humanlongevity.com.

Author contributions: J.C.V. conceived the study; A.T. and J.C.V. designed research; L.C.T.P., J.d.I., E.H.M.W., M.M.F., E.F.K., A.M., N.S., C.X., and E.S. performed research; S.C.B., N.B., C.G., G.M., B.A.P., F.J.O., and Y.T. contributed new reagents/analytic tools; W.H.B., M.M.F., and E.S. led the sequencing process; S.C.B., N.B., C.G., and G.M. built informatic annotation and technology infrastructures; B.A.P., F.J.O., and Y.T. supervised research; and A.T., J.d.I., E.H.M.W., E.F.K., and J.C.V. wrote the paper.

Reviewers: D.B.G., Columbia University; and S.W.S., The Hospital for Sick Children.

The authors are employees of Human Longevity, Inc.

Data deposition: Data access is granted through the Human Longevity, Inc. gene browser (HLI-OpenSearch.com). In addition, 325 NA12878 reference genome sequences have been donated to PrecisionFDA (https://precision.fda.gov).

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1613365113/-/DCSupplemental.

Freely available online through the PNAS open access option.


Batidas de coração humano são detectadas aos 16 dias de gestação

terça-feira, outubro 18, 2016

Calcium handling precedes cardiac differentiation to initiate the first heartbeat

Richard CV Tyser Antonio MA Miranda Chiann-mun Chen Sean M Davidson Shankar Srinivas Paul R Riley 

University of Oxford, United Kingdom; University College London and Medical School, United Kingdom; Wellcome Trust, United Kingdom

Published October 11, 2016

Cite as eLife 2016;5:e17113


The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca2+-oscillations (SACOs) in the forming cardiac crescent (stage E7.75) prior to overt beating. Nascent contraction initiated at around E8.0 and was associated with sarcomeric assembly and rapid Ca2+ transients, underpinned by sequential expression of the Na+-Ca2+ exchanger (NCX1) and L-type Ca2+ channel (LTCC). Pharmacological inhibition of NCX1 and LTCC revealed rapid development of Ca2+ handling in the early heart and an essential early role for NCX1 in establishing SACOs through to the initiation of beating. NCX1 blockade impacted on CaMKII signalling to down-regulate cardiac gene expression, leading to impaired differentiation and failed crescent maturation.

eLife digest

The heart is the first organ to form and to begin working in an embryo during pregnancy. It must begin pumping early to supply oxygen and nutrients to the developing embryo. Coordinated contractions of specialised muscle cells in the heart, called cardiomyocytes, generate the force needed to pump blood. The flow of calcium ions into and out of the cardiomyocytes triggers these heartbeats. In addition to triggering heart contractions, calcium ions also act as a messenger that drives changes in which genes are active in the cardiomyocytes and how these cells behave.

Scientists commonly think of the first heartbeat as occurring after a tube-like structure forms in the embryo that will eventually develop into the heart. However, it is not yet clear how the first heartbeat starts or how the initial heartbeats affect further heart development.

Tyser, Miranda et al. now show that the first heartbeat actually occurs much earlier in embryonic development than widely appreciated. In the experiments, videos of live mouse embryos showed that prior to the first heartbeat the flow of calcium ions between different cardiomyocytes is not synchronised. However, as the heart grows these calcium flows become coordinated leading to the first heartbeat. The heartbeats also become faster as the heart grows. Using drugs to block the movement of calcium ions, Tyser, Miranda et al. also show that a protein called NCX1 is required to trigger the calcium flows prior to the first heartbeat. Moreover, the experiments revealed that these early heartbeats help drive the growth of cardiomyocytes and shape the developing heart.

Together, the experiments show that the first heartbeats are essential for normal heart development. Future studies are needed to determine what controls the speed of the first heartbeats, and what organises the calcium flows that trigger the first heartbeat. Such studies may help scientists better understand birth defects of the heart, and may suggest strategies to rebuild hearts that have been damaged by a heart attack or other injury.


A evolução "refina" (ação teleológica) o DNA para benefício posterior das espécies: isso é Design Inteligente!

Genome-Wide Motif Statistics are Shaped by DNA Binding Proteins over Evolutionary Time Scales

Long Qian and Edo Kussell

Phys. Rev. X 6, 041009 – Published 14 October 2016

Source/Fonte: Physics


The composition of a genome with respect to all possible short DNA motifs impacts the ability of DNA binding proteins to locate and bind their target sites. Since nonfunctional DNA binding can be detrimental to cellular functions and ultimately to organismal fitness, organisms could benefit from reducing the number of nonfunctional DNA binding sites genome wide. Using in vitro measurements of binding affinities for a large collection of DNA binding proteins, in multiple species, we detect a significant global avoidance of weak binding sites in genomes. We demonstrate that the underlying evolutionary process leaves a distinct genomic hallmark in that similar words have correlated frequencies, a signal that we detect in all species across domains of life. We consider the possibility that natural selection against weak binding sites contributes to this process, and using an evolutionary model we show that the strength of selection needed to maintain global word compositions is on the order of point mutation rates. Likewise, we show that evolutionary mechanisms based on interference of protein-DNA binding with replication and mutational repair processes could yield similar results and operate with similar rates. On the basis of these modeling and bioinformatic results, we conclude that genome-wide word compositions have been molded by DNA binding proteins acting through tiny evolutionary steps over time scales spanning millions of generations.

Received 24 February 2016

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.

Published by the American Physical Society

FREE PDF GRATIS: Physical Review X Sup. Info.

A origem da multicelularidade: um pequeno salto de ancestrais unicelulares para animais

segunda-feira, outubro 17, 2016

High-Throughput Proteomics Reveals the Unicellular Roots of Animal Phosphosignaling and Cell Differentiation

Arnau Sebé-Pedrós 1, 8, Marcia Ivonne Peña 2, 4, Salvador Capella-Gutiérrez 3, 4, 5, Meritxell Antó 1, Toni Gabaldón 3, 4, 6, Iñaki Ruiz-Trillo 1, 6, 7, Eduard Sabidó 2, 4, 9 , 

1 Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Passeig Marítim de la Barceloneta 37-49, 08003 Barcelona, Spain

2 Proteomics Unit, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain

3 Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain

4 Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain

5 CBS Fungal Biodiversity Centre, Uppsalalaan 8, 3584 LT Utrecht, the Netherlands

6 ICREA, Pg. Lluis Companys 23, 08010 Barcelona, Spain

7 Departament de Genètica, Microbilogia i Estadística, Universitat de Barcelona, Avinguda Diagonal 643, 08028 Barcelona, Spain

Received 1 October 2015, Revised 17 July 2016, Accepted 16 September 2016, Available online 13 October 2016

Published: October 13, 2016


• Proteome remodeling is linked to temporal differentiation in a unicellular context

• Dynamic phosphosignaling underlies unicellular temporal differentiation

• Parallel evolution of Ser/Thr and Tyr kinase phosphoregulatory networks

• Cell-type-specific phosphoactivation of Tyr kinases in Capsaspora


Cell-specific regulation of protein levels and activity is essential for the distribution of functions among multiple cell types in animals. The finding that many genes involved in these regulatory processes have a premetazoan origin raises the intriguing possibility that the mechanisms required for spatially regulated cell differentiation evolved prior to the appearance of animals. Here, we use high-throughput proteomics in Capsaspora owczarzaki, a close unicellular relative of animals, to characterize the dynamic proteome and phosphoproteome profiles of three temporally distinct cell types in this premetazoan species. We show that life-cycle transitions are linked to extensive proteome and phosphoproteome remodeling and that they affect key genes involved in animal multicellularity, such as transcription factors and tyrosine kinases. The observation of shared features between Capsaspora and metazoans indicates that elaborate and conserved phosphosignaling and proteome regulation supported temporal cell-type differentiation in the unicellular ancestor of animals.


multicellularity; tyrosine kinase; signaling; origin of metazoa; evolution gene expression; mass spectrometry; proteomics; phosphoproteomics; Capsaspora; evolution

FREE PDF GRATIS: Developmental Cell

Michael Ruse (evolucionista honesto) 'falou e disse'- o Darwinismo é uma religião secular

Darwinism as religion: what literature tells us about evolution


Critics of the New Atheists argue that they are as religious as those whom they excoriate. Their writings show a polemical scorn for their opponents unknown outside those books of the Old Testament devoted to the prophets. It is not purely contingent that the world’s most famous non-believer, Richard Dawkins, author of the God Delusion, is also the world’s most famous evolutionist, Richard Dawkins, author of the Selfish Gene. The New Atheist creed is Darwinism, a secular world picture that dates to 1859, the year of publication of Charles Darwin’s Origin of Species.

The New Atheists deny this charge vehemently, so naturally as a philosopher interested in the relationship between science and religion I am attracted to the issue, and as an evolutionist I am convinced that understanding of the present demands understanding of the past. Hence, Darwinism as Religion: What Literature Tells Us About Evolution. I argue that, from the publication of the Origin, enthusiasts have been building a kind of secular religion based on its ideas, particularly on the dark world without ultimate meaning implied by the central mechanism of natural selection. Thus, I conclude that not only are the New Atheists in the secular-religion business, it would be very peculiar and historically anomalous if they were not.

Although I have been writing now for over forty years on Darwin and the revolution that he brought about, in Darwinism as Religion I use a strategy entirely new to me–and although obviously one familiar to scholars in English Literature basically ignored by full-time historians of science. I turn to British and American literature for insights, working from the great novelists and poets of the nineteenth century–George Eliot, Thomas Hardy, Emily Dickinson, and others–down to the writers of today–ending with the very different perspectives of the British novelist Ian McEwan and the American novelist Marilynne Robinson. By running through the concerns of conventional religions–God, origins, humans, race and class, morality, sex, sin and redemption, the future–I show how people thought (and continue to think) in ways that are as based on Darwin’s insights as they are on rejection of long-established doctrines, Christian doctrines in particular.

Take as an example that of proper behavior, ethics. Even before the Origin people worried about whether one could have morality without the Christian God. In Nemesis of Faith (1849), James Anthony Froude (brother of one of the closest associates of John Henry Newman) has his main character (an Anglican clergyman) lose his beliefs in Christianity and then follow a very morally dicey career entangled with another man’s wife. Even after the Origin, Darwin’s “bulldog” Thomas Henry Huxley–the father of agnosticism–argued for compulsory school bible study for its moral value. Yet the novelists, above all George Eliot, took up the challenge. Especially in her last full-length novel, Daniel Deronda (1876), through the behaviors of her two main characters–the beautiful but selfish Gwendolen Harleth and the conversely truly altruistic Daniel–Eliot shows how good behavior of a kind stressed by Darwin in his Descent of Man(1871) leads to happiness and how bad behavior leads only to misery. Morality is its own justification, a theme picked up by Mrs. Humphrey Ward (the former Julia Arnold, niece of the poet) in her smash-hit best-seller Robert Elsmere (1888). Her hero, another Anglican clergyman, likewise loses his faith (thanks in major part to Darwin) but not only remains loyal to his wife but takes up the satisfying role of a teacher in a kind of proto-YMCA night school for the working classes.

Just as we have the proselytizing Darwinian New Atheists, so we have today a vocal anti-Darwinian party, consisting somewhat surprising not only of the evangelical Christians of the American South but of some of today’s most eminent atheist philosophers, notably Thomas Nagel, OUP author of Mind and Cosmos: Why the Materialist Neo-Darwinian Conception of Nature is Almost Certainly False (2012). As his subtitle reveals, Nagel’s worry is less about the science and more about its supposed religious-cum-metaphysical implications, namely that Darwin plunges us into a hateful world without value and meaning. This kind of worry is shared by many students of the history of evolutionary theory, and–although unlike atheists who deny the existence of Jesus Christ one can hardly deny the existence of Charles Darwin–there is today a veritable cottage industry of writers proving that Darwin was unimportant and that there was no revolution bringing on evolution, certainly no Darwinian Revolution. As Darwin as Religion takes on the New Atheists Darwin idolizers, so also it takes on the Darwin deniers, arguing that there was a revolution, that Darwin was the key figure, and that, as is shown by the discussion of morality in the last paragraph, fears about godless materialism, stripped of meaning and value, are simply without historical foundation.


Michael Ruse was born in England in 1940. In 1962 he moved to Canada and taught philosophy for thirty-five years at the University of Guelph in Ontario, before taking his present position at Florida State University in 2000. He is a philosopher and historian of science, with a particular interest in Darwin and evolutionary biology. The author or editor of over fifty books and the founding editor of the journal Biology and Philosophy, he is a fellow of the Royal Society of Canada, a former Guggenheim Fellow and Gifford Lecturer, and the recipient of four honorary degrees.

Cientistas afirmam ter descoberto o que existia antes do início do universo

sábado, outubro 15, 2016

Non-singular and Cyclic Universe from the Modified GUP

Source/Fonte: Physics-Astronomy
In this paper, we investigate the effects of a new version of the generalized uncertainty principle (modified GUP) on the dynamics of the Universe. As the modified GUP will modify the relation between the entropy and area of the apparent horizon, it will also deform the Friedmann equations within Jacobson's approach. We explicitly find these deformed Friedmann equations governing the modified GUP-corrected dynamics of such a Universe. It is shown that the modified GUP-deformed Jacobson's approach implies an upper bound for the density of such a Universe. The Big Bang singularity can therefore also be avoided using the modified GUP-corrections to horizons' thermodynamics. In fact, we are able to analyze the pre Big Bang state of the Universe. Furthermore, the equations imply that the expansion of the Universe will come to a halt and then will immediately be followed by a contracting phase. When the equations are extrapolated beyond the maximum rate of contraction, a cyclic Universe scenario emerges.
Comments:22 pages, 2 figures
Subjects:General Relativity and Quantum Cosmology (gr-qc); High Energy Physics - Theory (hep-th)
Cite as:arXiv:1608.00560 [gr-qc]
 (or arXiv:1608.00560v2 [gr-qc] for this version)

Submission history

From: Fayçal Hammad [view email] 
[v1] Sat, 30 Jul 2016 03:40:35 GMT (429kb,D)
[v2] Wed, 3 Aug 2016 02:22:05 GMT (429kb,D)


Uma revisão radical da genética humana: muitas mutações gênicas 'mortais' estão se revelando inofensivas!

quarta-feira, outubro 12, 2016

A radical revision of human genetics

Why many ‘deadly’ gene mutations are turning out to be harmless.

Erika Check Hayden

12 October 2016

Illustration by Darren Hopes

Lurking in the genes of the average person are about 54 mutations that look as if they should sicken or even kill their bearer. But they don't. Sonia Vallabh hoped that D178N was one such mutation.

In 2010, Vallabh had watched her mother die from a mysterious illness called fatal familial insomnia, in which misfolded prion proteins cluster together and destroy the brain. The following year, Sonia was tested and found that she had a copy of the prion-protein gene,PRNP, with the same genetic glitch — D178N — that had probably caused her mother's illness. It was a veritable death sentence: the average age of onset is 50, and the disease progresses quickly. But it was not a sentence that Vallabh, then 26, was going to accept without a fight. So she and her husband, Eric Minikel, quit their respective careers in law and transportation consulting to become graduate students in biology. They aimed to learn everything they could about fatal familial insomnia and what, if anything, might be done to stop it. One of the most important tasks was to determine whether or not the D178N mutation definitively caused the disease.

Few would have thought to ask such a question in years past, but medical genetics has been going through a bit of soul-searching. The fast pace of genomic research since the start of the twenty-first century has packed the literature with thousands of gene mutations associated with disease and disability. Many such associations are solid, but scores of mutations once suggested to be dangerous or even lethal are turning out to be innocuous. These sheep in wolves' clothing are being unmasked thanks to one of the largest genetics studies ever conducted: the Exome Aggregation Consortium, or ExAC.

ExAC is a simple idea. It combines sequences for the protein-coding region of the genome — the exome — from more than 60,000 people into one database, allowing scientists to compare them and understand how variable they are. But the resource is having tremendous impacts in biomedical research. As well as helping scientists to toss out spurious disease–gene links, it is generating new discoveries. By looking more closely at the frequency of mutations in different populations, researchers can gain insight into what many genes do and how their protein products function.



Cruzamento entre Petrogales provoca o repensar da evolução

Gene flow despite complex Robertsonian fusions among rock-wallaby (Petrogale) species

Sally Potter, Craig Moritz, Mark D. B. Eldridge

Published 7 October 2015.DOI: 10.1098/rsbl.2015.0731

Source/Fonte: PhysOrg


Complex Robertsonian rearrangements, with shared arms in different fusions, are expected to prevent gene flow between hybrids through missegregation during meiosis. Here, we estimate gene flow between recently diverged and chromosomally diverse rock-wallabies (Petrogale) to test for this form of chromosomal speciation. Contrary to expectations, we observe relatively high admixture among species with complex fusions. Our results reinforce the need to consider alternative roles of chromosome change, together with genic divergence, in driving speciation.

FREE PDF GRATIS: Biology Letters

Mais um "relógio" encontrado em cianobactérias: mero acaso, fortuita necessidade ou design inteligente???

The cyanobacterial circadian clock is based on the intrinsic ATPase activity of KaiC

C. Robertson McClung *

Author Affiliations

Department of Biological Sciences, Dartmouth College, Hanover, NH 03755

The earth rotates on its axis with a period of 24 h, imposing a dramatic diurnal oscillation on the biosphere. Endogenous biological clocks with circadian periods of ≈24 h are nearly ubiquitous, from bacteria to humans, and serve to coordinate organisms with these daily environmental changes. These clocks make important contributions to fitness, and, in competitive environments, disruption of the circadian clock has dire consequences in cyanobacteria, plants, and mammals (1). Enormous progress has been made in elucidating the mechanism of circadian timekeeping in the cyanobacterium Synechococcus elongatus PCC 7942. The kaiABC locus is essential for rhythmicity (2), and recently a self-sustaining and temperature-compensated circadian rhythm in the phosphorylation of KaiC has been reconstituted in vitro in a minimal system containing the three Kai (Japanese for “cycle”) proteins plus ATP (3, 4). In a recent issue of PNAS, Terauchi et al. (5) established that the ATPase activity of KaiC is the fundamental reaction underlying the cyanobacterial circadian oscillation (Fig. 1).


Encontrado um "relógio" bioquímico celular: mero acaso, fortuita necessidade ou design inteligente???

Structure Volume 13, Issue 5, May 2005, Pages 735–741

Recent Cyanobacterial Kai Protein Structures Suggest a Rotary Clock

Jimin Wang

Under an Elsevier user license

Source/Fonte: Rolex

The cyanobacterial circadian oscillator, which controls internal daily periodicity, consists of three Kai proteins, KaiA, KaiB, and KaiC, in its oscillation feedback loop (Ishiura et al., 1998). KaiC is a negative element of the loop, repressing the expression of its own KaiBCand other global genes; KaiA is a positive element, releasing the repression. The discovery of a bacterial clock unexpectedly breaks the paradigm of biological clocks, because rapid cell division and chromosome duplication in bacteria occur within one circadian period ( Kondo et al., 1994 and Kondo et al., 1997). In fact, these cyanobacterial oscillators in individual cells have a strong temporal stability with a correlation time of several months (Mihalcescu et al., 2004). The cyanobacterial circadian system is the simplest of all clock forms and possesses the same three levels of organizations as do all other biological clocks: the generation of oscillation in its feedback loop, amplification of oscillating signals for gene expression, and coordination with daily environmental events (Harmer et al., 2001). Upon reviewing recent biochemical and structural studies, I shall provide insights into the inner working of this bacterial clock and provide evidence for a striking similarity between the Kai clock and the F1-ATPase system.

Analisando as profundidades da diversidade biológica durante o segundo século da publicação científica Genética

Probing the Depths of Biological Diversity During the Second Century of GENETICS

Linnea Sandell, Sarah P. Otto

GENETICS October 1, 2016 vol. 204 no. 2 395-400; 

After a century of GENETICS, we understand better than ever the diversity of life and its immense evolutionary history. Nevertheless, we are still gazing at the tip of the iceberg of biological complexity. For virtually every biological rule, an exception lies in some organism on some branch of the tree of life. Meiosis is fair. Mating is random. Chromosomes govern inheritance. The genetic code is universal. All have exceptions (meiotic drive: Buckler et al. 1999 and Didion et al. 2016; mating: Jiang et al. 2013; inheritance: Fang et al. 2012 and Houri-Ze’evi et al. 2016; genetic code: Saccone et al.2000). In contemplating what is in store for the journal GENETICS in its second century, we argue that our vision of genetics will move increasingly away from trying to understand the general pattern of biology toward grappling with its variability and, in so doing, better reveal the depths of biological complexity.
Biological complexity is often discussed as the product of an evolutionary history spanning the ∼4.1 billion years since the origin of life (Bell et al. 2015), but even this number is misleadingly small. Evolution is not linear: it branches into species, which explore, in parallel, different ways of surviving and reproducing. This exploration spans more than 1014 years of evolutionary discovery (Figure 1), a staggering number. By comparison, there are an estimated 1014 letters in total in all of the published books across human history (Urban 2014). It is no wonder that life is so variable.
Contemplating this breadth of evolutionary history is essential if one is to understand the richness of biology. Historically, we have done the reverse. We have stripped out the complexities, alternative contexts, and species interactions. This is a natural and necessary thing to do when first seeking out the impact of what a gene does or how a population evolves, but a full understanding of biology requires that we expand our viewpoint and consider alternative contexts and understudied organisms from across the tree of life. Why do genes not always perform in the same way? Why do populations not always evolve in the same direction? Although biologists, both theoreticians and empiricists, have been moving in this direction for decades, we argue that in the next century, our focus will shift from a search for general rules to a greater appreciation of biological variability. We describe ways in which we expect this shift to impact genetics and evolution.

Fazendo exceção com a eugenia humana - Mengele redivivus???

terça-feira, outubro 11, 2016

Taking Exception to Human Eugenics

Frederick P. Roth, John Wakeley

GENETICS October 1, 2016 vol. 204 no. 2 821-823; 


We are concerned that the Perspectives article “Mutation and Human Exceptionalism: Our Future Genetic Load” by Michael Lynch (2016) opens the dark chapter of eugenics without clearly reading it as a cautionary tale.
Given the history of eugenics, especially high standards for scholarship, sensitivity, and attention to historical context are needed when discussing the complex issues surrounding human genetic improvement. Statements similar to those Lynch makes in his article—which in the 1920s and 1930s were being made by leading population geneticists such as R. A. Fisher, J. B. S. Haldane, and H. J. Muller—led directly to eugenic policies and were later readily attached to the genocidal programs of Nazism (Kevles 1995). Failing to engage these issues, or offering vague recommendations, invites misappropriation by those who wish to see the return of an aggressive eugenics.
Lynch focuses on the rate and long-term consequences of deleterious mutations in humans. Despite concluding that humans are unexceptional in both germline and somatic mutation rates, he worries that deleterious mutations might accumulate in the future because of “exceptional” human behaviors that “thwart selection.” Specifically, by treating disease and reducing variation in the number of children per person, we reduce the impact of genetics on survival and procreation, and in turn threaten the “future of the human gene pool.”
Lynch contrasts deleterious mutations of large effect, which can be detected in parents or early-stage embryos (then “culled”), with mutations that are “impervious to detection” but have selective effects that can be ameliorated by medical intervention. We will refer to these as type 1 and type 2 mutations, respectively.
For type 1 mutations, Lynch quantifies the effectiveness of culling “in which a fraction fof the population is accurately screened for the mutation, with carrier chromosomes being culled upon detection.” He does not restrict this statement to prenatal screening, referring also to “direct screening in parents.” To be clear, Lynch did not advocate culling. However, he does ask us to entertain the idea, without specifically discussing the ethical minefield and horrifying history surrounding medical procedures without a net benefit to the recipient. For type 2 mutations, Lynch suggests that the extent to which we thwart selection is the extent to which “bad genes” will become prevalent and eventually exact their cost.
Some points in the article are argued poorly. On page 871, Lynch promises to back up the worrisome claim that our mutation rate is destined to increase, saying “...the possibility that the baseline human mutation rate will elevate over time (for reasons discussed below) motivates a strong argument...” yet he never delivers. Presumably “below” refers to the paragraph spanning the two columns of page 872, in which is it claimed that “hundreds of genetic loci influence the mutation rate either directly or indirectly,” without any citation. The paragraph ends with the statement: “It is therefore plausible that the human mutation rate is destined to slowly increase toward exceptional levels.” Despite Lynch’s additional promise early in the article (page 869) that “many of the issues addressed below were raised by Crow prior to the genomics revolution and can now be evaluated in a more quantitative way” (see Crow 19972000), there is no calculation here, only an undocumented claim of plausibility.

O que é interpretar uma teoria?

domingo, outubro 09, 2016

What is it to interpret a theory?

Dewar, Neil (2016) What is it to interpret a theory? [Preprint]


This paper seeks to give an account of what could be involved in interpreting a theory. The aim is to try and provide a robust conception of theory-interpretation which operates in terms internal to the representational architecture of the theory, rather than importing meaning by stipulative correspondence to external terms.


Uma visão CRISPR da função do genoma durante o desenvolvimento.

A CRISPR view of development

Melissa M. Harrison 1, Brian V. Jenkins 2, Kate M. O’Connor-Giles 3,4 and Jill Wildonger 2

- Author Affiliations

1 Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA;

2 Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA;

3 Laboratory of Genetics,

4 Laboratory of Cell and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA

Corresponding author: wildonger@wisc.edu


The CRISPR (clustered regularly interspaced short palindromic repeat)–Cas9 (CRISPR-associated nuclease 9) system is poised to transform developmental biology by providing a simple, efficient method to precisely manipulate the genome of virtually any developing organism. This RNA-guided nuclease (RGN)-based approach already has been effectively used to induce targeted mutations in multiple genes simultaneously, create conditional alleles, and generate endogenously tagged proteins. Illustrating the adaptability of RGNs, the genomes of >20 different plant and animal species as well as multiple cell lines and primary cells have been successfully modified. Here we review the current and potential uses of RGNs to investigate genome function during development.

Keywords CRISPR Cas9 development genome editing genome engineering RNA-guided nuclease


Freely available online through the Genes & Development Open Access option.

© 2014 Harrison et al.; Published by Cold Spring Harbor Laboratory Press

This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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