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Beyond Darwin: Evolvability and the Generation of Novelty Marc Kirschner
Kirschner M BMC Biology 2013, 11:110 http://www.biomedcentral.com/1741-7007/11/110 INTERVIEW Open Access Beyond Darwin: evolvability and the generation of novelty Marc Kirschner Marc Kirschner graduated in biochemistry from North- western University, moving to Berkeley for his doctoral research and with positions at Berkeley, Oxford Univer- sity and Princeton before he took a professorship at Uni- versity of California San Francisco where with Andrew Murray he did seminal research on the control of the cell cycle in Xenopus egg extracts that led to the discov- ery of how cyclin drives the cell cycle, and with Tim Mitchison on the dynamic instability of microtubules. In 1993 he moved to Harvard where in 2003 he became the founding Chair of the HMS Department of Systems Biology and was named the John Franklin Enders Uni- versity Professor in 2009. The two books he wrote with John Gerhart, Cells, Embryos and Evolution (Blackwell, 1997) and The Plausibility of Life: Resolving Darwin’sDi- lemma (Yale University Press, 2005), reflect his deep and longstanding interest in how biological systems evolve. Here he gives his view of the evolution of evolvability and its profound importance for understanding and ap- plying biology. What is evolvability - how would you define it? Marc Kirschner In some sort of tautological way evolvability is simply the capacity of a system to evolve. But more than that, in a Darwinian sense it speaks to both the amount of effectively what I mean is that if you make random variation that is subject to selection, and the nature of changes in mechanical systems they inevitably either that variation. -
The Drosophila MCPH1-B Isoform Is a Substrate of the APC E3 Ubiquitin Ligase Complex
ß 2014. Published by The Company of Biologists Ltd | Biology Open (2014) 3, 669–676 doi:10.1242/bio.20148318 RESEARCH ARTICLE The Drosophila MCPH1-B isoform is a substrate of the APCCdh1 E3 ubiquitin ligase complex Sarah G. Hainline`, Jamie L. Rickmyre`,*, Leif R. Neitzel, Laura A. Lee§ and Ethan Lee§ ABSTRACT and two primary co-activators, Cdc20 and Cdh1 (Kulkarni et al., 2013). Destruction of APC substrates is required in eukaryotes for The Anaphase-Promoting Complex (APC) is a multi-subunit E3 the initiation of anaphase and exit from mitosis. Cdc20 associates ubiquitin ligase that coordinates progression through the cell cycle by with the APC in early mitosis, leading to the destruction of temporally and spatially promoting the degradation of key proteins. proteins that control the onset of anaphase, whereas Cdh1 Many of these targeted proteins have been shown to play important promotes degradation of APC substrates that control late mitosis roles in regulating orderly progression through the cell cycle. Using and the following G1 phase. These co-activators provide APC a previously described Drosophila in vitro expression cloning substrate specificity by facilitating the recognition of specific approach, we screened for new substrates of the APC in Xenopus destruction motifs (e.g. degrons) such as the D-box (RxxLxxxxN) egg extract and identified Drosophila MCPH1 (dMCPH1), a protein or KEN box (Lys–Glu–Asn) (King et al., 1996; Min and Lindon, encoded by the homolog of a causative gene for autosomal recessive 2012; Pfleger and Kirschner, 2000). Mutations of these motifs primary microcephaly in humans. The dMCPH1-B splice form, but not block the recognition of the protein by the APC, preventing their the dMCPH1-C splice form, undergoes robust degradation in APC-mediated destruction. -
Carnival of Evolution #58: Visions of the Evolutionary Future Bradly Alicea Michigan State University
Carnival of Evolution #58: visions of the evolutionary future Bradly Alicea Michigan State University Originally published at: http://syntheticdaisies.blogspot.com on April 1, 2013 (http://syntheticdaisies.blogspot.com/2013/04/carnival-of-evolution-58-visions-of.html) Welcome to Carnival of Evolution! Now with albedo! Introduction What does the future look like? For some, the future is the place of constant progress and a place where dreams become reality. For others, the future is a scary, dystopian place. When actualized, however, future worlds fall somewhere in between these two visions. Can we make accurate projections about the future? As I pointed out in a Synthetic Daisies post from February [1], futurists and technologists have a pretty dismal track record at projecting future scenarios, and often get things notoriously wrong. UPPER LEFT: Ad from the 1982 opening of EPCOT Center, Florida. UPPER RIGHT: Dystopic future city from the movie "Idiocracy" (Inset is the cover of "Future Shock" by Alvin Toffler). BOTTOM LEFT: Bank of England Economic Forecast (circa 2011). BOTTOM RIGHT: New New York, circa 3000 (from the TV show "Futurama"). With visions of the future in mind, this month's Carnival of Evolution (#58) theme is the future of evolution. While a significant component of evolutionary biology involves reconstructing the past [2], we are actually (with error, of course) also predicting the future. Yet can we do any better than futurists or technologists? It is hard to say, and if you have opinions on this I would be glad to hear them. However, this month's CoE will address five themes that may (or may not) help us understand where the complexity of life is headed. -
Deptbiochemistry00ruttrich.Pdf
'Berkeley University o'f California Regional Oral History Office UCSF Oral History Program The Bancroft Library Department of the History of Health Sciences University of California, Berkeley University of California, San Francisco The UCSF Oral History Program and The Program in the History of the Biological Sciences and Biotechnology William J. Rutter, Ph.D. THE DEPARTMENT OF BIOCHEMISTRY AND THE MOLECULAR APPROACH TO BIOMEDICINE AT THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO VOLUME I With an Introduction by Lloyd H. Smith, Jr., M.D. Interviews by Sally Smith Hughes, Ph.D. in 1992 Copyright O 1998 by the Regents of the University of California Since 1954 the Regional Oral History Office has been interviewing leading participants in or well-placed witnesses to major events in the development of Northern California, the West, and the Nation. Oral history is a method of collecting historical information through tape-recorded interviews between a narrator with firsthand knowledge of historically significant events and a well- informed interviewer, with the goal of preserving substantive additions to the historical record. The tape recording is transcribed, lightly edited for continuity and clarity, and reviewed by the interviewee. The corrected manuscript is indexed, bound with photographs and illustrative materials, and placed in The Bancroft Library at the University of California, Berkeley, and in other research collections for scholarly use. Because it is primary material, oral history is not intended to present the final, verified, or complete narrative of events. It is a spoken account, offered by the interviewee in response to questioning, and as such it is reflective, partisan, deeply involved, and irreplaceable. -
Darwin's Unfinished Symphony: How Culture Made the Human Mind By
June 2018 NEW BIOLOGICAL BOOKS 151 and permanent exposure of the human penis, the the experimental data, I am compelled to question phenomenon of orgasm, and a social, not solely re- the runaway process—the fundamental premise of productive, function of sex. He suggests that human much of Prum’s book. pairbonding evolved by females’ choice of males that With that significant reservation, I heartily recom- provided more sexual pleasure—the human male’s mend The Evolution of Beauty as an immensely stim- equivalent of a pheasant’s plumes. Finally, Prum sug- ulating treatment of a wide range of issues. As a gests that female sexual autonomy can account for biologist and birder, I was enthralled by the author’s variation in human sexual orientation. He makes descriptions of a range of species and their displays, the important point that same-sex attraction proba- such as the extraordinary club-winged manakin and bly did not substantially lower reproductive success the legendary great argus (which, to my great disap- for most of human evolution: even today, many ho- pointment, I am unlikely ever to see). Biology teach- mosexual men marry and raise families to mitigate ers would do well to read Prum’s story of the sexually stigma and meet social expectations. The author antagonistic evolution of duck genitalia: it will cap- supposes that like most traits, variation in sexual ori- ture the most indifferent student’simagination.The entation may result from variation at many genetic ideas and evidence the author provides about the loci and in many environmental (social) factors. -
Science in School the European Journal for Science Teachers Autumn 2017 | Issue 41 | Issue 2017 Autumn
Subscribe free in Europe: FREE www.scienceinschool.org Science in School The European journal for science teachers Autumn 2017 | Issue 41 2017 Autumn DesignDesign inspirationinspiration TheThe secretssecrets ofof sharkshark skinskin ISSN: 1818-0353 www.scienceinschool.org ISSN: 1818-0353 www.scienceinschool.org INSPIREINSPIRE SupportingSupporting AfricanAfrican science:science: the role of fruit flies Published and funded by EIROforum by funded and Published the role of fruit flies TEACHTEACH AA particleparticle acceleratoraccelerator inin youryour saladsalad bowlbowl Image courtesy of Ariane Böhm / Grunwald Kadow lab Kadow of Ariane Böhm / Grunwald Image courtesy Image courtesy of Andrew Burgess / shutterstock.com Burgess of Andrew Image courtesy SUPPORTING AFRICAN SCIENCE: 35 HOW DO BIRDS FLY? 38 THE ROLE OF FRUIT FLIES A HANDS-ON DEMONSTRATION Not only is the fruit fly a valuable model Dissect a chicken from the supermarket organism, but it is also helping to put Africa to discover the unusual pulley system that on the scientific world map. enables birds to fly. Image courtesy of Stefan Pircher / Shutterstock Pircher of Stefan Image courtesy DESIGN INSPIRATION: THE SECRETS OF SHARK SKIN 19 Shark skin is adapted for energy-efficient swimming in remarkable ways, some of which are now being copied by designers and engineers. UNDERSTAND INSPIRE 4 News from the EIROs: Exotic particles, 35 Supporting African science: fusion-device ashtrays and lunar missions the role of fruit flies 8 Cellulose: from trees to treats TEACH 13 Gravitational -
Experimental Evolution of Escherichia Coli Harboring an Ancient Translation Protein
J Mol Evol DOI 10.1007/s00239-017-9781-0 ORIGINAL ARTICLE Experimental Evolution of Escherichia coli Harboring an Ancient Translation Protein Betül Kacar1,2 · Xueliang Ge3 · Suparna Sanyal3 · Eric A. Gaucher4,5 Received: 8 October 2016 / Accepted: 30 January 2017 © The Author(s) 2017. This article is published with open access at Springerlink.com Abstract The ability to design synthetic genes and engi- We subsequently evolved replicate hybrid bacterial popula- neer biological systems at the genome scale opens new tions for 2000 generations in the laboratory and examined means by which to characterize phenotypic states and the adaptive response via fitness assays, whole genome the responses of biological systems to perturbations. One sequencing, proteomics, and biochemical assays. Hybrid emerging method involves inserting artificial genes into lineages exhibit a general adaptive strategy in which the bacterial genomes and examining how the genome and its fitness cost of the ancient gene was ameliorated in part by new genes adapt to each other. Here we report the devel- upregulation of protein production. Our results suggest that opment and implementation of a modified approach to an ancient–modern recombinant method may pave the way this method, in which phylogenetically inferred genes are for the synthesis of organisms that exhibit ancient pheno- inserted into a microbial genome, and laboratory evolu- types, and that laboratory evolution of these organisms may tion is then used to examine the adaptive potential of the prove useful in elucidating insights into historical adaptive resulting hybrid genome. Specifically, we engineered an processes. approximately 700-million-year-old inferred ancestral vari- ant of tufB, an essential gene encoding elongation factor Tu, and inserted it in a modern Escherichia coli genome in Background place of the native tufB gene. -
Interpretation: Hemichordates May Have No “Notochord”
iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 3 Part 3. How did the Chordate get its chord (notochord)? Marc Kirschner Dept. of Systems Biology Harvard Medical School Boston Massachusetts The Spemann experiment and the vertebrate specific development What about the notochord? Interpretation: Hemichordates • The crux of Bateson’s argument that hemichordates were essentially chordates. may have no “notochord”. • Virtually every marker of the vertebrate notochord is present in the hemichordate (chordin, noggin, admp, brachyury, hedgehog….) • Small problem, they are not in the hemichordate stromachord. The American Society for Cell Biology 1 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 3 But does it have a Spemann Organizer? Though the organizer gives rise to the notochord in vertebrates, it is in fact also a complex signaling center. The hemichordate expresses genes of the chordate prechordal endo-mesoderm (otx, dmbx, ttf2, hex, gsc…), and at the appropriate A/P map position. ttf2/foxE2 dmbx Interpretation: as a signaling center, the hemichordate has an organizer otx The vertebrate organizer is a tripartite structure of signaling centers The American Society for Cell Biology 2 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 3 But these organizer signaling centers are initially dispersed in hemichordates The vertebrate organizer is a composit of three distinct signaling centers in hemichordates • The vertebrate organizer is complex, since it conflates dorsal/ventral -
The Man Who Bottled Evolution
NEWSFOCUS EAST LANSING, MICHIGAN—When most biologists want to understand how evolu- tion unfolds, they look for clues in the fossil The Man Who record or the natural world. Richard Lenski simply walks across his Michigan State Uni- versity lab to his freezers. There, stored in Bottled Evolution 4000 vials, are bacteria dating back to 1988. That was the year Lenski started a simple but radical experiment. He put samples of Richard Lenski’s 25-year experiment in bacterial evolution Escherichia coli into a sugar solution, stop- shows no signs of running out of surprises about how pered the flasks, and waited to see what mutation and selection shape living things would happen. It was a study with no defi ned endpoint, so risky that he didn’t try very hard to get outside funding for it. After 25 years and 58,000 bacterial generations, Lenski’s bacteria are still growing, mutating, and evolving. They are proving as critical to understanding the workings of evolution as classic paleontology studies such as Stephen Jay Gould’s research on the pace of change in mollusks. Lenski’s humble E. coli have shown, among other things, how multiple small mutations can prepare the ground for a major change; how new species can arise and diverge; and that Gould was mistaken on November 24, 2013 when he claimed that, given a second chance, evolution would likely take a completely different course. Most recently, the colonies have demonstrated that, contrary to what many biologists thought, evolution never comes to a stop, even in an unchanging environment. -
The Invention of Courts the Unstable Biomedical Research Ecosystem
american academy of arts & sciences spring 2015 www.amacad.org vol. lxviii, no. 3 american academy of arts & sciences bulletin spring 2015 Bulletin Academy Report Explores the State of the Humanities in Higher Education The Invention of Courts Jamal Greene, Carol S. Steiker, Susan S. Silbey, Linda Greenhouse, Jonathan Lippman, and Judith Resnik The Unstable Biomedical Research Ecosystem: How Can It Be Made More Robust? Mark C. Fishman, Nancy C. Andrews, Sally Kornbluth, Susan R. Wente, Richard H. Brodhead, Harold Varmus, and Tania Baker ALSO: Replenishing the Innovation Pipeline: The Role of University Research Mr g–The Story of Creation as Told by God Policy Perspective on the Police Use of Lethal Force On the Professions In Memoriam: David Frohnmayer Upcoming Events JUNE NOVEMBER 15th 17th Washington, DC Cambridge, MA The Ritz-Carlton Georgetown House of the Academy Reception for Washington, DC, Chamber Series Area Fellows and Guests in collaboration with the Welcome Newly Elected Fellows Cantata Singers Made in America: Songs by Barber, OCTOBER Copland, and Fine 9th–11th Cambridge, MA Induction Weekend 9th A Celebration of the Arts and Humanities 10th Induction Ceremony 11th Academic Symposium For updates and additions to the calendar, visit www.amacad.org. Special Thanks e recently completed another successful fund-raising year with more than W$6.7 million raised. The Annual Fund surpassed $1.7 million, a record-break- ing total. Gifts from all other sources–including grants for projects–totaled more than $5 million. We are grateful for the generosity of an increasing number of contributors–including members, staff, and friends; foundations, corporations, and associations; and Univer- sity Affiliates–who made these results possible. -
Ibioseminars: Marc Kirschner, March 2008 the Origin of Vertebrates, Part 2 the American Society for Cell Biology 1
iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 2 Part 2. Telling the back from the front or what the chordates invented Marc Kirschner Dept. of Systems Biology Harvard Medical School Boston Massachusetts The position of the CNS has been used to define the body plan of organisms But what does that say for an organism that has a clear D/V axis but no centralized nervous system? The American Society for Cell Biology 1 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 2 Using the standard convention call the mouth, ventral Dorsal Mouth Ventral BMP, a form of TGF-β, is involved in D/V patterning BMP and anti-BMP (chordin, sog) are conserved in neural specification in flies and frogs What role do they have in hemichordates which have no CNS? The American Society for Cell Biology 2 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 2 The genes that are patterned by BMP in the vertebrate neural tube are not conserved in Saccoglossus Shh responsive bmp responsive Yet, every detail of the BMP gradient seems fundamental to D/V patterning What is the BMP pathway being used for? The American Society for Cell Biology 3 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 2 siRNA is a powerful tool in for answering such questions So radialized the dorsal structure that holds the proboscis to the collar doesn’t form Knockdown of BMP causes ventral radialized embryos and the proboscis falls off. Increased BMP dorsalizes The American Society for Cell Biology 4 iBioSeminars: -
Aesthetic Evolution by Mate Choice: Darwin's Really Dangerous Idea
Phil. Trans. R. Soc. B (2012) 367, 2253–2265 doi:10.1098/rstb.2011.0285 Review Aesthetic evolution by mate choice: Darwin’s really dangerous idea Richard O. Prum* Department of Ecology and Evolutionary Biology, and Peabody Museum of Natural History, Yale University, New Haven, CT 06520, USA Darwin proposed an explicitly aesthetic theory of sexual selection in which he described mate pre- ferences as a ‘taste for the beautiful’, an ‘aesthetic capacity’, etc. These statements were not merely colourful Victorian mannerisms, but explicit expressions of Darwin’s hypothesis that mate prefer- ences can evolve for arbitrarily attractive traits that do not provide any additional benefits to mate choice. In his critique of Darwin, A. R. Wallace proposed an entirely modern mechanism of mate preference evolution through the correlation of display traits with male vigour or viability, but he called this mechanism natural selection. Wallace’s honest advertisement proposal was stri- dently anti-Darwinian and anti-aesthetic. Most modern sexual selection research relies on essentially the same Neo-Wallacean theory renamed as sexual selection. I define the process of aes- thetic evolution as the evolution of a communication signal through sensory/cognitive evaluation, which is most elaborated through coevolution of the signal and its evaluation. Sensory evaluation includes the possibility that display traits do not encode information that is being assessed, but are merely preferred. A genuinely Darwinian, aesthetic theory of sexual selection requires the incor- poration of the Lande–Kirkpatrick null model into sexual selection research, but also encompasses the possibility of sensory bias, good genes and direct benefits mechanisms.