Origem molecular da suscetibilidade fraca da velocidade da cinesina a cargas e sua relação ao comportamento coletivo das cinesinas

Molecular origin of the weak susceptibility of kinesin velocity to loads and its relation to the collective behavior of kinesins

Qian Wang a, Michael R. Diehl b,c, Biman Jana d, Margaret S. Cheung a,e, Anatoly B. Kolomeisky a,b,c, and José N. Onuchic a,c,f,g,1 

Author Affiliations

a Center for Theoretical Biological Physics, Rice University, Houston, TX 77005;

b Department of Bioengineering, Rice University, Houston, TX 77030;

c Department of Chemistry, Rice University, Houston, TX 77030;

d Department of Physical Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India;

e Department of Physics, University of Houston, Houston, TX 77204;

f Department of Physics and Astronomy, Rice University, Houston, TX 77005;

g Department of Biosciences, Rice University, Houston, TX 77005

Contributed by José N. Onuchic, September 2, 2017 (sent for review June 7, 2017; reviewed by Ioan Andricioaei and Garegin A. Papoian)

Fig. S3. Illustration of the ATP binding pocket defined in the simulation. The motor head is colored in cyan, and ATP is colored in yellow. The ATP binding pocket is defined as beads within 10 Å around the ATP surface, which are colored in red.

Significance

Successful functioning of biological systems depends on efficient cellular transport supported by several classes of active biological molecules known as motor proteins. Although they have been intensively studied using various experimental methods, their molecular properties remain not fully understood. We developed a theoretical approach by using structure-based molecular dynamics simulations. It allowed us to understand at the molecular level the effect of external forces on kinesin motor proteins. It is shown that a force-regulated coupling between the neck linker and the ATP binding site of a kinesin accounts for experimentally observed weak susceptibility to loads. Our framework helps us to rationalize the low cooperativity among kinesins. The presented method is a powerful tool in clarifying microscopic features of motor proteins.

Abstract

Motor proteins are active enzymatic molecules that support important cellular processes by transforming chemical energy into mechanical work. Although the structures and chemomechanical cycles of motor proteins have been extensively investigated, the sensitivity of a motor’s velocity in response to a force is not well-understood. For kinesin, velocity is weakly influenced by a small to midrange external force (weak susceptibility) but is steeply reduced by a large force. Here, we utilize a structure-based molecular dynamic simulation to study the molecular origin of the weak susceptibility for a single kinesin. We show that the key step in controlling the velocity of a single kinesin under an external force is the ATP release from the microtubule-bound head. Only under large loading forces can the motor head release ATP at a fast rate, which significantly reduces the velocity of kinesin. It underpins the weak susceptibility that the velocity will not change at small to midrange forces. The molecular origin of this velocity reduction is that the neck linker of a kinesin only detaches from the motor head when pulled by a large force. This prompts the ATP binding site to adopt an open state, favoring ATP release and reducing the velocity. Furthermore, we show that two load-bearing kinesins are incapable of equally sharing the load unless they are very close to each other. As a consequence of the weak susceptibility, the trailing kinesin faces the challenge of catching up to the leading one, which accounts for experimentally observed weak cooperativity of kinesins motors.

kinesin molecular mechanism susceptibility collective behavior

Footnotes

1To whom correspondence should be addressed. Email: jonuchic@rice.edu.

Author contributions: Q.W., M.S.C., A.B.K., and J.N.O. designed research; Q.W. performed research; Q.W., M.R.D., B.J., M.S.C., A.B.K., and J.N.O. analyzed data; and Q.W., M.R.D., B.J., M.S.C., A.B.K., and J.N.O. wrote the paper.

Reviewers: I.A., University of California, Irvine; and G.A.P., University of Maryland.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1710328114/-/DCSupplemental.

Copyright © 2017 the Author(s). Published by PNAS.

This is an open access article distributed under the PNAS license.

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O grande suspiro materialista de Darwin sobre a origem da vida: o destino das nucleobases em pequenos lagos quentes

Origin of the RNA world: The fate of nucleobases in warm little ponds

Ben K. D. Pearce a,b,1, Ralph E. Pudritz a,b,c,d, Dmitry A. Semenov c, and Thomas K. Henning c 

Author Affiliations

a Origins Institute, McMaster University, Hamilton, ON L8S 4M1, Canada;

b Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1, Canada;

c Planet and Star Formation Department, Max Planck Institute for Astronomy, 69117 Heidelberg, Germany;

d Institute for Theoretical Astrophysics, Center for Astronomy Heidelberg, 69120 Heidelberg, Germany

Edited by Donald E. Canfield, Institute of Biology and Nordic Center for Earth Evolution, University of Southern Denmark, Odense M., Denmark, and approved August 28, 2017 (received for review June 7, 2017)

Significance

There are currently two competing hypotheses for the site at which an RNA world emerged: hydrothermal vents in the deep ocean and warm little ponds. Because the former lacks wet and dry cycles, which are well known to promote polymerization (in this case, of nucleotides into RNA), we construct a comprehensive model for the origin of RNA in the latter sites. Our model advances the story and timeline of the RNA world by constraining the source of biomolecules, the environmental conditions, the timescales of reaction, and the emergence of first RNA polymers.

Abstract

Before the origin of simple cellular life, the building blocks of RNA (nucleotides) had to form and polymerize in favorable environments on early Earth. At this time, meteorites and interplanetary dust particles delivered organics such as nucleobases (the characteristic molecules of nucleotides) to warm little ponds whose wet–dry cycles promoted rapid polymerization. We build a comprehensive numerical model for the evolution of nucleobases in warm little ponds leading to the emergence of the first nucleotides and RNA. We couple Earth’s early evolution with complex prebiotic chemistry in these environments. We find that RNA polymers must have emerged very quickly after the deposition of meteorites (less than a few years). Their constituent nucleobases were primarily meteoritic in origin and not from interplanetary dust particles. Ponds appeared as continents rose out of the early global ocean, but this increasing availability of “targets” for meteorites was offset by declining meteorite bombardment rates. Moreover, the rapid losses of nucleobases to pond seepage during wet periods, and to UV photodissociation during dry periods, mean that the synthesis of nucleotides and their polymerization into RNA occurred in just one to a few wet–dry cycles. Under these conditions, RNA polymers likely appeared before 4.17 billion years ago.

life origins astrobiology planetary science meteoritics RNA world

Footnotes

1 To whom correspondence should be addressed. Email: pearcbe@mcmaster.ca.

Author contributions: B.K.D.P., R.E.P., D.A.S., and T.K.H. designed research; B.K.D.P. performed research; B.K.D.P. and R.E.P. analyzed data; and B.K.D.P., R.E.P., D.A.S., and T.K.H. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

See Commentary on page 11264.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1710339114/-/DCSupplemental.

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Flutuações de não equilíbrio de membranas lipídicas pela proteína motora rotativa F1F0-ATP sintase

Nonequilibrium fluctuations of lipid membranes by the rotating motor protein F1F0-ATP synthase

Víctor G. Almendro-Vedia a,b, Paolo Natale a,b, Michael Mell a, Stephanie Bonneau c, Francisco Monroy a,b, Frederic Joubert c, and Iván López-Montero a,b,1 

Author Affiliations

a Departamento Química Física I, Universidad Complutense de Madrid, 28040 Madrid, Spain;

b Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain;

c Laboratoire Jean Perrin, CNRS, Université Pierre et Marie Curie, 75005 Paris, France

Edited by Olaf S. Andersen, Weill Cornell Medical College, New York, NY, and accepted by Editorial Board Member Ramon Latorre September 7, 2017 (received for review January 23, 2017)

Significance

The shape of biological membranes is constantly remodeled and maintained out of equilibrium by active proteins. The functional capacity of membrane deformation is mainly determined by the mechanical interplay between protein activity and bending elasticity. In our experiments, we find that ATP synthase, a rotating membrane protein that synthesizes the biochemical energy in cells through proton-pumping activity across the membrane, promotes localized nonequilibrium membrane fluctuations when reconstituted in giant lipid vesicles. The large membrane deformations emerge from the pumping action of rotating proteins clustered at specific emplacements in the membrane. Our results pave the way to new experimental realizations to explore the collective effects of rotating ATP synthases and their possible biological implications for biomembrane organization and protein functionality.

Abstract

ATP synthase is a rotating membrane protein that synthesizes ATP through proton-pumping activity across the membrane. To unveil the mechanical impact of this molecular active pump on the bending properties of its lipid environment, we have functionally reconstituted the ATP synthase in giant unilamellar vesicles and tracked the membrane fluctuations by means of flickering spectroscopy. We find that ATP synthase rotates at a frequency of about 20 Hz, promoting large nonequilibrium deformations at discrete hot spots in lipid vesicles and thus inducing an overall membrane softening. The enhanced nonequilibrium fluctuations are compatible with an accumulation of active proteins at highly curved membrane sites through a curvature−protein coupling mechanism that supports the emergence of collective effects of rotating ATP synthases in lipid membranes.

giant vesicles active membranes mechanical properties flickering spectroscopy biological nanorotors

Footnotes

1To whom correspondence should be addressed. Email: ivanlopez@quim.ucm.es.

Author contributions: I.L.-M. designed research; V.G.A.-V. and P.N. performed research; M.M. and F.M. contributed new reagents/analytic tools; V.G.A.-V., S.B., F.M., F.J., and I.L.-M. analyzed data; and P.N., S.B., F.M., F.J., and I.L.-M. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. O.S.A. is a guest editor invited by the Editorial Board.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1701207114/-/DCSupplemental.

Copyright © 2017 the Author(s). Published by PNAS.

This is an open access article distributed under the PNAS license.

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Visualizando a atividade nuclear do RNAi em células vivas humanas

Visualizing nuclear RNAi activity in single living human cells

Shira Avivi a,b, Amir Mor a,b, Iris Dotan c, Sivan Tzadok c, Itamar Kanter a,b, Noa Kinor a,b, Dan Canaani c, and Yaron Shav-Tal a,b,1 

Author Affiliations

a The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel;

b Institute of Nanotechnology, Bar-Ilan University, Ramat Gan 5290002, Israel;

c Department of Biochemistry & Molecular Biology, Faculty of Life Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel

Edited by Robert H. Singer, Albert Einstein College of Medicine, Bronx, NY, and approved September 11, 2017 (received for review May 4, 2017)

Significance

RNA interference (RNAi) is a natural process occurring in cells, and is used to silence genes. Typically, RNAi occurs via small RNA molecules generated in the cell nucleus, which are exported to the cytoplasm where they silence messenger RNA (mRNA) molecules. However, RNAi is thought to occur in the nucleus as well. To demonstrate that this process can occur in the nucleus and to determine its dynamics, we generated human cell systems that enabled us to image living cells and to track gene silencing as it transpired in real time. We found that the RNAi machinery can target the mRNA as it is being transcribed, and that silencing is mediated through modifications occurring on histone proteins bound to the DNA.

Abstract

Nuclear RNA interference (RNAi) is mediated by the canonical RNAi machinery and can lead to transcriptional silencing, transcriptional activation, or modulation of alternative splicing patterns. These effects transpire through changes in histone and DNA modifications via RNAi-mediated recruitment of chromatin-modifying enzymes. To prove that nuclear RNAi occurs and modulates transcription in human cells, we used live-cell imaging to detect and track nuclear RNAi transcriptional repression in single living human cells. While employing reporter genes constructed with inducible promoters and cognate-inducible short hairpin RNA (shRNA) targeted against the reporter coding region, we have characterized the dynamics of the nuclear RNAi process in living human cells. We show that the silencing effect is mediated through the nascent mRNA, followed by activity of histone methylating enzymes, but not through DNA methylation.

transcription nuclear RNAi histone methylation live-cell imaging argonautes

Footnotes

1To whom correspondence should be addressed. Email: Yaron.Shav-Tal@biu.ac.il.

Author contributions: S.A., A.M., I.D., D.C., and Y.S.-T. designed research; S.A., A.M., I.D., S.T., and N.K. performed research; S.A., A.M., I.D., and I.K. analyzed data; and Y.S.-T. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1707440114/-/DCSupplemental.

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Predição de novo de estruturas de cromossomos humanos - padrões de marcação epigenéticos codificam a arquitetura do genoma

De novo prediction of human chromosome structures: Epigenetic marking patterns encode genome architecture

Michele Di Pierro a,1,2, Ryan R. Cheng a,1, Erez Lieberman Aiden a,b, Peter G. Wolynes a,c,d, and José N. Onuchic a,d,2 

Author Affiliations

a Center for Theoretical Biological Physics, Rice University, Houston, TX 77005;

b Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030;

c Department of Chemistry, Rice University, Houston, TX 77005;

d Department of Physics & Astronomy, Rice University, Houston, TX 77005

Contributed by José N. Onuchic, October 4, 2017 (sent for review August 24, 2017; reviewed by Jie Liang and Tamar Schlick)

Significance

In the nucleus of eukaryotic cells, the genome is organized in three dimensions in an architecture that depends on cell type. This organization is a key element of transcriptional regulation, and its disruption often leads to disease. We demonstrate that it is possible to predict how a genome will fold based on the epigenetic marks that decorate chromatin. Epigenetic marking patterns are used to predict the corresponding ensemble of 3D structures by leveraging both energy landscape theory and neural network-based machine learning. These predictions are extensively validated by the results of DNA-DNA ligation assays and fluorescence microscopy, which are found to be in exceptionally good agreement with theory.

Abstract

Inside the cell nucleus, genomes fold into organized structures that are characteristic of cell type. Here, we show that this chromatin architecture can be predicted de novo using epigenetic data derived from chromatin immunoprecipitation-sequencing (ChIP-Seq). We exploit the idea that chromosomes encode a 1D sequence of chromatin structural types. Interactions between these chromatin types determine the 3D structural ensemble of chromosomes through a process similar to phase separation. First, a neural network is used to infer the relation between the epigenetic marks present at a locus, as assayed by ChIP-Seq, and the genomic compartment in which those loci reside, as measured by DNA-DNA proximity ligation (Hi-C). Next, types inferred from this neural network are used as an input to an energy landscape model for chromatin organization [Minimal Chromatin Model (MiChroM)] to generate an ensemble of 3D chromosome conformations at a resolution of 50 kilobases (kb). After training the model, dubbed Maximum Entropy Genomic Annotation from Biomarkers Associated to Structural Ensembles (MEGABASE), on odd-numbered chromosomes, we predict the sequences of chromatin types and the subsequent 3D conformational ensembles for the even chromosomes. We validate these structural ensembles by using ChIP-Seq tracks alone to predict Hi-C maps, as well as distances measured using 3D fluorescence in situ hybridization (FISH) experiments. Both sets of experiments support the hypothesis of phase separation being the driving process behind compartmentalization. These findings strongly suggest that epigenetic marking patterns encode sufficient information to determine the global architecture of chromosomes and that de novo structure prediction for whole genomes may be increasingly possible.

epigenetics machine learning energy landscape theory genomic architecture Hi-C

Footnotes

1M.D.P. and R.R.C. contributed equally to this work.

2To whom correspondence may be addressed. Email: michele.dipierro@rice.edu or jonuchic@rice.edu.

Author contributions: M.D.P., R.R.C., E.L.A., P.G.W., and J.N.O. designed research; M.D.P. and R.R.C. performed research; M.D.P. and R.R.C. contributed new reagents/analytic tools; M.D.P., R.R.C., E.L.A., P.G.W., and J.N.O. analyzed data; and M.D.P., R.R.C., E.L.A., P.G.W., and J.N.O. wrote the paper.

Reviewers: J.L., University of Illinois at Chicago; and T.S., New York University.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1714980114/-/DCSupplemental.

Copyright © 2017 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

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Do Australopithecus ao Homo: a transição que não houve!

From Australopithecus to Homo: the transition that wasn't

William H. Kimbel, Brian Villmoare

Published 13 June 2016. DOI: 10.1098/rstb.2015.0248

Source/Fonte: Natural History Museum - London

Abstract

Although the transition from Australopithecus to Homo is usually thought of as a momentous transformation, the fossil record bearing on the origin and earliest evolution of Homo is virtually undocumented. As a result, the poles of the transition are frequently attached to taxa (e.g. A. afarensis, at ca 3.0 Ma versus H. habilis or H. erectus, at ca 2.0–1.7 Ma) in which substantial adaptive differences have accumulated over significant spans of independent evolution. Such comparisons, in which temporally remote and adaptively divergent species are used to identify a ‘transition’, lend credence to the idea that genera should be conceived at once as monophyletic clades and adaptively unified grades. However, when the problem is recast in terms of lineages, rather than taxa per se, the adaptive criterion becomes a problem of subjectively privileging ‘key’ characteristics from what is typically a stepwise pattern of acquisition of novel characters beginning in the basal representatives of a clade. This is the pattern inferred for species usually included in early Homo, including H. erectus, which has often been cast in the role as earliest humanlike hominin. A fresh look at brain size, hand morphology and earliest technology suggests that a number of key Homo attributes may already be present in generalized species of Australopithecus, and that adaptive distinctions in Homo are simply amplifications or extensions of ancient hominin trends.

This article is part of the themed issue ‘Major transitions in human evolution’.

Whether primeval man, when he possessed very few arts of the rudest kind, and when his power of language was extremely imperfect, would have deserved to be called man, must depend on the definition which we employ. In a series of forms graduating insensibly from some ape-like creature to man as he now exists it would be impossible to fix on any definite point when the term ‘man’ ought to be used.

—Charles Darwin [2, p. 235]

The descent of man, and selection in relation to sex.

It seems to me more likely that H[omo] habilis and H. erectus, as well as some of the australopithecines, were all evolving along their own distinct lines by Lower Pleistocene times. This would mean that their shared common ancestor must be sought in the more remote past and that when such examples of the parent stock are found they will not much resemble any one of the three subsequent branches.

—Louis Leakey [3, p. 1280]

‘Homo habilis, Homo erectus and the australopithecines’.

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O ponto de vista diferencial das relações genótipo-fenótipo

HYPOTHESIS AND THEORY ARTICLE

Front. Genet., 19 May 2015 | https://doi.org/10.3389/fgene.2015.00179

The differential view of genotype–phenotype relationships

Virginie Orgogozo1*, Baptiste Morizot2 and Arnaud Martin3

1 CNRS, UMR 7592, Institut Jacques Monod, Université Paris Diderot, Paris, France

2 Aix Marseille Université, CNRS, CEPERC UMR 7304, Aix en Provence, France

3 Department of Molecular Cell Biology, University of California, Berkeley, CA, USA

FIGURE 2. Three current graphical representations of GP maps. (A) The early version of the GP map proposed by Lewontin (1974a). (B) A GP map where each point represents a single individual (Houle et al., 2010; Gjuvsland et al., 2013; Salazar-Ciudad and Marín-Riera, 2013). (C) The relationships between traits and genes, as depicted by Wagner (1996). See text for details.

We sometimes seem to have forgotten that the original question in genetics was not what makes a protein but rather ‘what makes a dog a dog, a man a man.’

Denis Noble, 2006

Abstract

An integrative view of diversity and singularity in the living world requires a better understanding of the intricate link between genotypes and phenotypes. Here we re-emphasize the old standpoint that the genotype–phenotype (GP) relationship is best viewed as a connection between two differences, one at the genetic level and one at the phenotypic level. As of today, predominant thinking in biology research is that multiple genes interact with multiple environmental variables (such as abiotic factors, culture, or symbionts) to produce the phenotype. Often, the problem of linking genotypes and phenotypes is framed in terms of genotype and phenotype maps, and such graphical representations implicitly bring us away from the differential view of GP relationships. Here we show that the differential view of GP relationships is a useful explanatory framework in the context of pervasive pleiotropy, epistasis, and environmental effects. In such cases, it is relevant to view GP relationships as differences embedded into differences. Thinking in terms of differences clarifies the comparison between environmental and genetic effects on phenotypes and helps to further understand the connection between genotypes and phenotypes.

FREE PDF GRATIS: Frontiers in Genetics

A cinesina gira de forma unidirecional e gera torque ao caminhar sobre microtúbulos: mero acaso, fortuita necessidade ou design inteligente?

Kinesin rotates unidirectionally and generates torque while walking on microtubules

Avin Ramaiya a,1, Basudev Roy a,1,2, Michael Bugiel a, and Erik Schäffer a,3 

Author Affiliations

a Cellular Nanoscience, Center for Plant Molecular Biology, University of Tübingen, 72076 Tübingen, Germany

Edited by J. Richard McIntosh, University of Colorado, Boulder, CO, and approved August 22, 2017 (received for review April 26, 2017)

Source/Fonte: MakeAGIF

Significance

Given the importance of cytoskeletal motor proteins, we asked whether translational motors rotate while walking along their tracks. Using an optical tweezers-based approach, we simultaneously measured translation, force, rotation, and torque of a kinesin motor with molecular resolution. We found that the gait followed a rotary stepping mechanism that generates torque and spins cargo. Thus, during walking, the motor “tail (and organelle) will tend to wind up like the rubber band of a toy airplane,” as Joe Howard hypothesized in 1996. To determine the overall motor efficiency, our measurements also point to the importance of accounting for rotational work. Apart from other cytoskeletal motors, the technique may be applied to molecular machines such as DNA motors and rotary engines like the ATP synthase.

Abstract

Cytoskeletal motors drive many essential cellular processes. For example, kinesin-1 transports cargo in a step-wise manner along microtubules. To resolve rotations during stepping, we used optical tweezers combined with an optical microprotractor and torsion balance using highly birefringent microspheres to directly and simultaneously measure the translocation, rotation, force, and torque generated by individual kinesin-1 motors. While, at low adenosine 5′-triphosphate (ATP) concentrations, motors did not generate torque, we found that motors translocating along microtubules at saturating ATP concentrations rotated unidirectionally, producing significant torque on the probes. Accounting for the rotational work makes kinesin a highly efficient machine. These results imply that the motor’s gait follows a rotary hand-over-hand mechanism. Our method is generally applicable to study rotational and linear motion of molecular machines, and our findings have implications for kinesin-driven cellular processes.

kinesin optical tweezers polarization microscopy birefringence rotation

Footnotes

1A.R. and B.R. contributed equally to this work.

2Present address: Department of Physics, Indian Institute of Technology, Madras 600036, India.

3To whom correspondence should be addressed. Email: Erik.Schaeffer@uni-tuebingen.de.

Author contributions: E.S. designed research; A.R., B.R., and M.B. performed research; A.R., B.R., M.B., and E.S. analyzed data; and A.R., B.R., and E.S. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1706985114/-/DCSupplemental.

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Testando a hipótese neutra da evolução fenotípica

Testing the neutral hypothesis of phenotypic evolution

Wei-Chin Hoa, Yoshikazu Ohyab, and Jianzhi Zhanga,1 

Author Affiliations

a Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109;

b Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba Prefecture 277-8562, Japan

Edited by Wen-Hsiung Li, Academia Sinica, Taipei, Taiwan, and approved October 6, 2017 (received for review June 29, 2017)

Source/Fonte: Amazon Books

Significance

Despite the universal recognition that adaptation by Darwinian selection can shape phenotypic variations within and between species, it remains unknown whether most phenotypic variations observed have adaptive values, in part because addressing this question requires examining a large, random set of traits while past studies were biased toward traits that are likely adaptive. Here, we study 210 yeast morphological traits chosen purely on the basis of experimental feasibility and expression levels of all yeast genes with reliable measurements. We find that morphological variations, but not expression variations, are largely adaptive, suggesting that different classes of phenotypic traits are subject to adaptive evolution to varying extents.

Abstract

Although evolution by natural selection is widely regarded as the most important principle of biology, it is unknown whether phenotypic variations within and between species are mostly adaptive or neutral due to the lack of relevant studies of large, unbiased samples of phenotypic traits. Here, we examine 210 yeast morphological traits chosen because of experimental feasibility irrespective of their potential adaptive values. Our analysis is based on the premise that, under neutrality, the rate of phenotypic evolution measured in the unit of mutational size declines as the trait becomes more important to fitness, analogous to the neutral paradigm that functional genes evolve more slowly than functionless pseudogenes. However, we find faster evolution of more important morphological traits within and between species, rejecting the neutral hypothesis. By contrast, an analysis of 3,466 gene expression traits fails to refute neutrality. Thus, at least in yeast, morphological evolution appears largely adaptive, but the same may not apply to other classes of phenotypes. Our neutrality test is applicable to other species, especially genetic model organisms, for which estimations of mutational size and trait importance are relatively straightforward.

adaptation gene expression morphology neutrality yeast

Footnotes

1To whom correspondence should be addressed. Email: jianzhi@umich.edu.

Author contributions: W.-C.H. and J.Z. designed research; W.-C.H. and Y.O. performed research; Y.O. contributed new reagents/analytic tools; W.-C.H. analyzed data; and W.-C.H. and J.Z. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1710351114/-/DCSupplemental.

Published under the PNAS license.

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Sobre a origem da construção biológica com um foco na multicelularidade: mero acaso, fortuita necessidade ou design inteligente?

On the origin of biological construction, with a focus on multicellularity

Jordi van Gestel a,b,c,d and Corina E. Tarnita e,1 

Author Affiliations

a Department of Evolutionary Biology and Environmental Studies, University of Zürich, 8057 Zürich, Switzerland;

b Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;

c Department of Environmental Systems Science, ETH Zürich, 8092 Zürich, Switzerland;

d Department of Environmental Microbiology, Swiss Federal Institute of Aquatic Science and Technology (EAWAG), 8600 Dübendorf, Switzerland;

e Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544

Edited by Gene E. Robinson, University of Illinois at Urbana–Champaign, Urbana, IL, and approved September 1, 2017 (received for review April 9, 2017)

Abstract

Biology is marked by a hierarchical organization: all life consists of cells; in some cases, these cells assemble into groups, such as endosymbionts or multicellular organisms; in turn, multicellular organisms sometimes assemble into yet other groups, such as primate societies or ant colonies. The construction of new organizational layers results from hierarchical evolutionary transitions, in which biological units (e.g., cells) form groups that evolve into new units of biological organization (e.g., multicellular organisms). Despite considerable advances, there is no bottom-up, dynamical account of how, starting from the solitary ancestor, the first groups originate and subsequently evolve the organizing principles that qualify them as new units. Guided by six central questions, we propose an integrative bottom-up approach for studying the dynamics underlying hierarchical evolutionary transitions, which builds on and synthesizes existing knowledge. This approach highlights the crucial role of the ecology and development of the solitary ancestor in the emergence and subsequent evolution of groups, and it stresses the paramount importance of the life cycle: only by evaluating groups in the context of their life cycle can we unravel the evolutionary trajectory of hierarchical transitions. These insights also provide a starting point for understanding the types of subsequent organizational complexity. The central research questions outlined here naturally link existing research programs on biological construction (e.g., on cooperation, multilevel selection, self-organization, and development) and thereby help integrate knowledge stemming from diverse fields of biology.

major evolutionary transitions hierarchical evolutionary transitions bottom-up approach life cycle animal sociality

Footnotes

1To whom correspondence should be addressed. Email: ctarnita@princeton.edu.

Author contributions: J.v.G. and C.E.T. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1704631114/-/DCSupplemental.

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Captura de imagens a laser e profundo sequenciamento revelam os programas transcriptômicos regulando o início à diferenciação do pâncreas e fígado em embriões humanos

Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos

Rachel E. Jennings, Andrew A. Berry, David T. Gerrard, Stephen J. Wearne, James Strutt, Sarah Withey, Mariya Chhatriwala, Karen Piper Hanley, Ludovic Vallier, Nicoletta Bobola, Neil A. Hanley'Correspondence information about the author Neil A. HanleyEmail the author Neil A. Hanley

Published Online: October 19, 2017

Open Access

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DOI: http://dx.doi.org/10.1016/j.stemcr.2017.09.018 | 

Open access funded by Wellcome Trust

Article Info

Publication History

Published: October 19, 2017 Accepted: September 25, 2017

Received in revised form: September 22, 2017 Received: April 25, 2017

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Highlights

• Transcriptomic signatures at the inception of human liver and pancreas development

• Limited conservation of pancreas-enriched gene expression between human and mouse

• Human PSC protocols imply a dorsal rather than a ventral pancreatic program

• New pancreatic transcription factors imputed by differential analysis

Summary

To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation.

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Dawkins disse que o design na natureza é ilusão, mas a engenharia inspirada nela é, de facto, a ciência do Design Inteligente!!!

Ultra-antireflective synthetic brochosomes

Shikuan Yang, Nan Sun, Birgitt Boschitsch Stogin, Jing Wang, Yu Huang & Tak-Sing Wong

Nature Communications 8, Article number: 1285 (2017)

doi:10.1038/s41467-017-01404-8

Download Citation

Bioinspired materials Colloids Optical materials and structures

Received: 05 March 2017 Accepted: 14 September 2017

Published online: 03 November 2017

Abstract

Since the early discovery of the antireflection properties of insect compound eyes, new examples of natural antireflective coatings have been rare. Here, we report the fabrication and optical characterization of a biologically inspired antireflective surface that emulates the intricate surface architectures of leafhopper-produced brochosomes—soccer ball-like microscale granules with nanoscale indentations. Our method utilizes double-layer colloidal crystal templates in conjunction with site-specific electrochemical growth to create these structures, and is compatible with various materials including metals, metal oxides, and conductive polymers. These brochosome coatings (BCs) can be designed to exhibit strong omnidirectional antireflective performance of wavelengths from 250 to 2000 nm, comparable to the state-of-the-art antireflective coatings. Our results provide evidence for the use of brochosomes as a camouflage coating against predators of leafhoppers or their eggs. The discovery of the antireflective function of BCs may find applications in solar energy harvesting, imaging, and sensing devices.

Acknowledgements

We thank Josh Stapleton from Materials Characterization Laboratory and Leland Shawn Burghard at The Pennsylvania State University for the help with the optical measurements and the greenhouse management, respectively. We acknowledge funding support by the Defense Advanced Research Projects Agency Award# D14AP00042 (materials and optical characterizations), the National Science Foundation CAREER Award# 1351462 (materials fabrication), Start-Up Fund from The Pennsylvania State University, and Wormley Family Early Career Professorship. Stogin acknowledges support from the NSF Graduate Research Fellowship (Grant No.: DGE1255832). Publication of this article was funded in part by The Pennsylvania State University Libraries Open Access Publishing Fund. Part of the work was conducted at the Penn State node of the NSF-funded National Nanotechnology of Infrastructure Network.

Author information

Affiliations

Department of Mechanical and Nuclear Engineering, The Pennsylvania State University, University Park, PA, 16802, USA

Shikuan Yang, Nan Sun, Birgitt Boschitsch Stogin, Jing Wang, Yu Huang & Tak-Sing Wong

Materials Research Institute, The Pennsylvania State University, University Park, PA, 16802, USA

Shikuan Yang, Nan Sun, Birgitt Boschitsch Stogin, Jing Wang, Yu Huang & Tak-Sing Wong

Institute for Composites Science Innovation, School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027, China

Shikuan Yang

Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA

Tak-Sing Wong

Contributions

S.Y. and T.-S.W. designed the experiments. S.Y. carried out the materials fabrication, wetting, and optical characterizations. S.Y., N.S., B.B.S., J.W., and Y.H. conducted the data analysis. N.S. and J.W. performed vision simulations of various organisms and experimental verifications. S.Y., B.B.S., and T.-S.W. wrote the paper. All authors contributed to paper revision.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Shikuan Yang or Tak-Sing Wong.

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Estrutura tridimensional do flagelo/cília eucariótico por tomografia crio-eletrônica: mero acaso, fortuita necessidade ou design inteligente?

BIOPHYSICS

Vol. 9 (2013) p. 141-148

DOI: http://doi.org/10.2142/biophysics.9.141

Review Article

3D structure of eukaryotic flagella/cilia by cryo-electron tomography

Takashi Ishikawa1)

1) Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen PSI

Released on J-STAGE 2013/10/17 

Received 2013/07/09 Accepted 2013/09/25

Keywords: dynein, microtubule, cryo-EM, axoneme, motor protein

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Ajuste fino de cílios e flagelos móveis: a evolução das proteínas do motor de dineína de plantas aos seres humanos em alta resolução: mero acaso, fortuita necessidade ou design inteligente?

Fine-Tuning Motile Cilia and Flagella: Evolution of the Dynein Motor Proteins from Plants to Humans at High Resolution 

Martin Kollmar

Molecular Biology and Evolution, Volume 33, Issue 12, 1 December 2016, Pages 3249–3267, https://doi.org/10.1093/molbev/msw213

Published: 07 October 2016

Abstract

The flagellum is a key innovation linked to eukaryogenesis. It provides motility by regulated cycles of bending and bend propagation, which are thought to be controlled by a complex arrangement of seven distinct dyneins in repeated patterns of outer- (OAD) and inner-arm dynein (IAD) complexes. Electron tomography showed high similarity of this axonemal repeat pattern across ciliates, algae, and animals, but the diversity of dynein sequences across the eukaryotes has not yet comprehensively been resolved and correlated with structural data. To shed light on the evolution of the axoneme I performed an exhaustive analysis of dyneins using the available sequenced genome data. Evidence from motor domain phylogeny allowed expanding the current set of nine dynein subtypes by eight additional isoforms with, however, restricted taxonomic distributions. I confirmed the presence of the nine dyneins in all eukaryotic super-groups indicating their origin predating the last eukaryotic common ancestor. The comparison of the N-terminal tail domains revealed a most likely axonemal dynein origin of the new classes, a group of chimeric dyneins in plants/algae and Stramenopiles, and the unique domain architecture and origin of the outermost OADs present in green algae and ciliates but not animals. The correlation of sequence and structural data suggests the single-headed class-8 and class-9 dyneins to localize to the distal end of the axonemal repeat and the class-7 dyneins filling the region up to the proximal heterodimeric IAD. Tracing dynein gene duplications across the eukaryotes indicated ongoing diversification and fine-tuning of flagellar functions in extant taxa and species.

axoneme, cilium, flagellum, dynein, last eukaryotic common ancestor.

Issue Section: Discoveries

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A tomografia crio-eletrônica revela características conservadas de microtúbulos duplos em flagelos: mero acaso, fortuita necessidade ou design inteligente?

Cryo-electron tomography reveals conserved features of doublet microtubules in flagella

Daniela Nicastro a,1, Xiaofeng Fu a,b, Thomas Heuser a, Alan Tso a, Mary E. Porter c, and Richard W. Linck c 

Author Affiliations

Edited by J. Richard McIntosh, University of Colorado, Boulder, CO, and approved August 24, 2011 (received for review May 3, 2011)

Fig. 1. Cryo-ET provides an overview of the 3D structure of DMTs. Tomographic slices (A and B) and isosurface renderings (D–F) of averaged axonemal repeats from Chlamydomonas pseudo-WT (pWT; Table 1) show cross-sectional (A and D), longitudinal (B), and oblique (E and F) views of the DMT. The red lines in A indicate the cutting plane of the slice shown in B. In the surface renderings, only the DMT core is shown, whereas all peripheral structures [e.g., inner or outer dynein arm (IDA or ODA, respectively)] were removed but their positions are indicated in A (surface rendering overview with associated structures is shown in Fig. S1). PF numbers [according to Linck and Stephens (16)] are colored pink in the A-tubule (At) and dark blue in the B-tubule (Bt). In B, prominent left-handed helical lines with an 8-nm axial periodicity are apparent, probably corresponding to the helical lattice of tubulin subunits (28, 49). The IJ and trimeric outer junction (OJ) have distinct structures. Colored arrowheads point to MIP1 (light blue), MIP2 (red), MIP3 (yellow), and MIP4 (orange). DMT cross-sections are viewed from a proximal orientation (flagellar base) toward a distal (flagellar tip) orientation, and in the longitudinal view, the left side is proximal. The DMT orientations, labels, and colors shown here are used consistently in all subsequent figures unless otherwise noted and are valid for all panels. (C) Resolution of the DMT averages used in this study ranged from 3.3 to 3.9 nm (0.5 criterion of the Fourier shell correlation method). More details are provided in Table 1. (Scale bar: 10 nm.)

Abstract

The axoneme forms the essential and conserved core of cilia and flagella. We have used cryo-electron tomography of Chlamydomonas and sea urchin flagella to answer long-standing questions and to provide information about the structure of axonemal doublet microtubules (DMTs). Solving an ongoing controversy, we show that B-tubules of DMTs contain exactly 10 protofilaments (PFs) and that the inner junction (IJ) and outer junction between the A- and B-tubules are fundamentally different. The outer junction, crucial for the initiation of doublet formation, appears to be formed by close interactions between the tubulin subunits of three PFs with unusual tubulin interfaces; other investigators have reported that this junction is weakened by mutations affecting posttranslational modifications of tubulin. The IJ consists of an axially periodic ladder-like structure connecting tubulin PFs of the A- and B-tubules. The recently discovered microtubule inner proteins (MIPs) on the inside of the A- and B-tubules are more complex than previously thought. They are composed of alternating small and large subunits with periodicities of 16 and/or 48 nm. MIP3 forms arches connecting B-tubule PFs, contrary to an earlier report that MIP3 forms the IJ. Finally, the “beak” structures within the B-tubules of Chlamydomonas DMT1, DMT5, and DMT6 are clearly composed of a longitudinal band of proteins repeating with a periodicity of 16 nm. These findings, discussed in relation to genetic and biochemical data, provide a critical foundation for future work on the molecular assembly and stability of the axoneme, as well as its function in motility and sensory transduction.

microtubule stability cilia axoneme ciliopathies cytoskeleton

Footnotes

1To whom correspondence should be addressed. E-mail: nicastro@brandeis.edu.

Author contributions: D.N. designed research; D.N., X.F., T.H., and A.T. performed research; M.E.P. contributed new reagents/analytic tools; D.N., X.F., T.H., and R.W.L. analyzed data; and D.N. and R.W.L. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

See Author Summary on page 17249.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1106178108/-/DCSupplemental.

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