Science Literature

Nature 444, 243-244 (16 November 2006) | doi:10.1038/444243b; Published online 15 November 2006

Order for microbes
Abstract

Burgeoning microbial gene data require coherent efforts to make them readily usable.

Microbes don't subscribe to the single life. They are coupled with complex ecosystems of diverse, mutually dependent species. This complexity and the vast numbers of microbes in the ocean, the soil, in our gut and almost everywhere else pose a challenge to those seeking to understand microbial ecology.

In the 1980s, surveying the microbial world by sequencing the collective ribosomal RNA opened up new avenues. For the first time it was possible to get a glimpse of the make-up of complex microbial systems. It's a reasonable assumption that the more similar these sequences are, the more closely related the microbes are, and the more closely related their lifestyles must be - hence the pursuit of insights into what microbes might be doing in their environments.

But this assumption turned out to be fragile, as it emerged that microbes frequently shuffle around their genes both within and between species. A similarity in one gene does not necessarily correlate with the absence or presence of other genes in the genome.

Fortunately, the continuous decrease in sequencing costs allows today's microbiologists to sequence not only a single gene from each of the most abundant species in a microbial ecosystem, but also, at least in theory, all the genes present. These composite genomes, or 'metagenomes', provide a wealth of information that could only be dreamt of even a couple of years ago. With sequencing facilities continuing to increase their capacities by applying new technologies, and funding agencies supplying the necessary resources, sequencing the ocean or the contents of the human gut has become relatively easy. But how to extract meaningful information from a metagenome, and to gain insight into both the individual species' impact on the microbial community and the impact of this community on the ecosystem?

We can hope to unravel the function of every gene when individual species can be cultivated and genetically manipulated in the laboratory, but this is impossible when dealing with a complex community containing hundreds or thousands of species. Functional assignment of genes needs to be performed, even when the only information available is a string of nucleotide bases.

There are numerous databases and websites, public and not-so-public, some adhering to an easily understandable framework of standards and regulation, and some not so transparent. Five years ago it was a big disappointment to compare one's chosen sequence with the GenBank database and not find a 'hit'. Today there is a feeling of sheer inadequacy in the face of vast quantities of sequence and annotation information - and an acute need for a degree in bioinformatics.

Publication in most cases (including the Nature journals) requires the deposition of sequence data into the GenBank or EMBL databases. Much less effort is spent depositing unpublished data or updating information that is already published. In all probability, in the not too distant future, metagenomic studies will be done not only by the big sequencing centres, but by anybody with a reasonable research budget and university support. To make all the data more easily accessible, it would be desirable to have a collaborative effort of genome centres and funding agencies to build a universal microbial-sequence database, with a readily comprehensible framework for sequencing and annotation standards and regulations.

Microbiology has come a long way from investigating the easily cultured individual microbe from a rich microbial community and describing what is out there, and is now starting to get a grip on what they actually do. With the intrinsic difficulties of dealing with complex systems, it is good to see a field galvanized by new technologies and scientific daring. But more infrastructural order is required, to prevent the discipline getting ahead of itself.

The Archean-Paleoproterozoic transition (dated ca. 2500-2000 Ma) is commonly associated with the establishment of an oxygen-rich atmosphere and the emergence of an aerobic biosphere. The paper below considers rocks at the very beginning of this period and finds in oil-bearing fluid inclusions abundant evidence for photosynthesising eukaryotes. Some have claimed evidences back to 3700 Ma, but this represents the minority. However, this paper will make it easier to defend the claim that photosynthesis is found early in the Archaean. The gradualistic evolutionary story does not fit these data.

Biomarkers from Huronian oil-bearing fluid inclusions: An uncontaminated record of life before the Great Oxidation Event.
Adriana Dutkiewicz, Herbert Volk, Simon C. George, John Ridley and Roger Buick
Geology: 2006, Vol. 34, No. 6, pp. 437-440.

ABSTRACT: We report detailed molecular geochemistry of oil-bearing fluid inclusions from a ca. 2.45 Ga fluvial metaconglomerate of the Matinenda Formation at Elliot Lake, Canada. The oil, most likely derived from the conformably overlying McKim Formation, was trapped in quartz and feldspar during diagenesis and early metamorphism of the host rock, probably before ca. 2.2 Ga. The presence of abundant biomarkers for cyanobacteria and eukaryotes derived from and trapped in rocks deposited before the Great Oxidation Event is consistent with an earlier evolution of oxygenic photosynthesis than previously thought and suggests that some aquatic settings had become sufficiently oxygenated for sterol biosynthesis by this time. It also implies that eukaryotes survived several extreme climatic events, including the Paleoproterozoic "snowball Earth" glaciations. The extraction of biomarker molecules from Paleoproterozoic oil-bearing fluid inclusions thus establishes a new method, using low detection limits and system blank levels, to trace evolution of life through Earth's early history that avoids the potential contamination problems affecting shale-hosted hydrocarbons.

C. G. Kurland and colleagues sever the link between eukaryotes and prokaryotes in this recent article in Science. Their title refers to the "Irreducible Nature of Eukaryote Cells". The logic of their argument confirms this: the structures and the genetics of eukaryotes mean that an evolutionary pathway from prokaryotes must be rejected. However, they do not again use the word "irreducible" in their paper. What is clear is that the "simple" pathway that the textbooks have proclaimed for years must now be abandoned.

Genomics and the Irreducible Nature of Eukaryote Cells
C. G. Kurland, L. J. Collins, and D. Penny Science 312, 19 May 2006: 1011-1014.

Abstract: Large-scale comparative genomics in harness with proteomics has substantiated fundamental features of eukaryote cellular evolution. The evolutionary trajectory of modern eukaryotes is distinct from that of prokaryotes. Data from many sources give no direct evidence that eukaryotes evolved by genome fusion between archaea and bacteria. Comparative genomics shows that, under certain ecological settings, sequence loss and cellular simplification are common modes of evolution. Subcellular architecture of eukaryote cells is in part a physical-chemical consequence of molecular crowding; subcellular compartmentation with specialized proteomes is required for the efficient functioning of proteins.

Comparative genomics and proteomics have strengthened the view that modern eukaryote and prokaryote cells have long followed separate evolutionary trajectories. Because their cells appear simpler, prokaryotes have traditionally been considered ancestors of eukaryotes (1*4). Nevertheless, comparative genomics has confirmed a lesson from paleontology: Evolution does not proceed monotonically from the simpler to the more complex (5*9). Here, we review recent data from proteomics and genome sequences suggesting that eukaryotes are a unique primordial lineage.

Mitochondria, mitosomes, and hydrogenosomes are a related family of organelles that distinguish eukaryotes from all prokaryotes (10). Recent analyses also suggest that early eukaryotes had many introns (11, 12), and RNAs and proteins found in modern spliceosomes (13). Indeed, it seems that life-history parameters affect intron numbers (14, 15). In addition, "molecular crowding" is now recognized as an important physical-chemical factor contributing to the compartmentation of even the earliest eukaryote cells (16, 17).

Nuclei, nucleoli, Golgi apparatus, centrioles, and endoplasmic reticulum are examples of cellular signature structures (CSSs) that distinguish eukaryote cells from archaea and bacteria. Comparative genomics, aided by proteomics of CSSs such as the mitochondria (18, 19), nucleoli (20, 21), and spliceosomes (13, 22), reveals hundreds of proteins with no orthologs evident in the genomes of prokaryotes; these are the eukaryotic signature proteins (ESPs) (23, 24). The many ESPs within the subcellular structures of eukaryote cells provide landmarks to track the trajectory of eukaryote genomes from their origins. In contrast, hypotheses that attribute eukaryote origins to genome fusion between archaea and bacteria (25*30) are surprisingly uninformative about the emergence of the cellular and genomic signatures of eukaryotes (CSSs and ESPs). The failure of genome fusion to directly explain any characteristic feature of the eukaryote cell is a critical starting point for studying eukaryote origins.

Jonathan Wells explains how intelligent design theory may lead to new approaches to cancer research in this article from Rivista di Biologia / Biology Forum 98 (2005), pp. 71-96.

Abstract. A microtubule-dependent polar ejection force that pushes chromosomes away from spindle poles during prometaphase is observed in animal cells but not in the cells of higher plants. Elongating microtubules and kinesin-like motor molecules have been proposed as possible causes, but neither accounts for all the data. In the hypothesis proposed here a polar ejection force is generated by centrioles, which are found in animals but not in higher plants. Centrioles consist of nine microtubule triplets arranged like
the blades of a tiny turbine. Instead of viewing centrioles through the spectacles of molecular reductionism and neo-Darwinism, this hypothesis assumes that they are holistically designed to be turbines. Orthogonally oriented centriolar turbines could generate oscillations in spindle microtubules that resemble the motion produced by a laboratory vortexer. The result would be a microtubule-mediated ejection force tending to move chromosomes away from the spindle axis and the poles. A rise in intracellular calcium at the
onset of anaphase could regulate the polar ejection force by shutting down the centriolar turbines, but defective regulation could result in an excessive force that contributes to the chromosomal instability characteristic of most cancer cells.

Keywords. Centriole; Centrosome; Polar ejection force; Chromosomal instability;
Cancer.

Reviewed by Dennis Wagner

You would be violating the law to require students to read Vij Sodera?s One Small Speck to Man in the Dover County Schools, PA. Not because it is religious (Sodera never mentions God or the Bible), and not because it promotes creation-science or intelligent design (you won?t find those words anywhere in the book), but because this surgeon from the UK, with a special interest in animal biology, provides a detailed and devastating critique of evolution theory. And in Dover, PA the Federal judge ruled that the school district cannot require students to read anything that denigrates the theory of evolution.

In this encyclopedic book, Dr. Sodera explores the living world from coelacanths to embryology; from dinosaurs to muscle contraction; from whales to human fossils; and shows conclusively that the ?one small speck to man? theory of evolution is more imagination than reality. With 464 pages and over 800 color images, this truly outstanding work deals purely with the scientific evidence and provides a highly detailed reference.

Some readers may already be familiar with many of the critiques of Darwin?s theory presented in this book. However, to have them nicely organized in one volume, with outstanding photos and graphics to illustrate the points, makes this a wonderful high school or college level text, as well as a prized coffee table book that is fun to browse. Like most full-color coffee-table books, this volume will cost you a chunk of change. But we think you will find it a worthwhile investment, especially if you are a homeschool teacher looking for a life-sciences textbook that does not assume that Darwinian evolution is the only way to look at the evidence. The topics covered in individual chapters include animal fossils, time, mass extinctions, variation, DNA and proteins, molecular machines, whales, birds, the eye, human fossils, bipedalism, chromosomes, and intelligence.

The chapter on Human Fossils was particularly interesting as Dr. Sodera pictorially and analytically compares human-like fossils with modern man. His conclusion: ?So the human-like fossil evidence actually paints a completely different picture from that which is commonly portrayed. Instead of man evolving from apes via crude-looking ancestors, the evidence points to populations of ancient human beings having passed through some morphological changes (whether from inbreeding and/or disease) before these groups gained the modern human form.?

This is the third major book critiquing evolution to come out of the UK in recent years joining Dawkin?s God: Genes, Memes and the Meaning of Life by Alister McGrath, and Evolution Under the Microscope: A Scientific Critique of the Theory of Evolution by David Swift. Perhaps there is a movement brewing in the UK similar to the ID movement in the US.

Order your copy of One Small Speck to Man: the evolution myth.

Nature 438, 504-507 (24 November 2005)

Design principles of a bacterial signalling network

Markus Kollmann, Linda Lovdok, Kilian Bartholome, Jens Timmer1, and Victor Sourjik

Abstract: Cellular biochemical networks have to function in a noisy environment using imperfect components. In particular, networks involved in gene regulation or signal transduction allow only for small output tolerances, and the underlying network structures can be expected to have undergone evolution for inherent robustness against perturbations. Here we combine theoretical and experimental analyses to investigate an optimal design for the signalling network of bacterial chemotaxis, one of the most thoroughly studied signalling networks in biology. We experimentally determine the extent of intercellular variations in the expression levels of chemotaxis proteins and use computer simulations to quantify the robustness of several hypothetical chemotaxis pathway topologies to such gene expression noise. We demonstrate that among these topologies the experimentally established chemotaxis network of Escherichia coli has the smallest sufficiently robust network structure, allowing accurate chemotactic response for almost all individuals within a population.

Revealing the mystery of the bacterial flagellum:
A self-assembling nanomachine with fine switching capability
JAPAN NANONET BULLETIN - 11th Issue - February 5, 2004

Keiichi NAMBA
Professor, Graduate School of Frontier Biosciences, Osaka University
(Issued in Japanese: March 25, 2003)

(the online article contains links to many fasinating animations of the bacterial flagellum)

Nature created a rotary motor with a diameter of 30 nm. Motility of bacteria, such as Salmonella and E. coli with a body size of 1 to 2 micron, is driven by rapid rotation of a helical propeller by such a tiny little motor at its base. This organelle is called the flagellum, made of a rotary motor and a thin helical filament that grows up to about 15 micron. It rotates at around 20,000 rpm, at energy consumption of only around 10 to 16 W and with energy conversion efficiency close to 100 percent. Prof. Nambas research group is going to reveal the mechanism of this highly efficient flagellar motor that is far beyond the capabilities of artificial motors.

The flagellum is made by self-assembly of about 25 different proteins. The rotor ring made of protein FliF is the first to assemble in the cytoplasmic membrane. Then, other protein molecules attach to the ring one after another from the base to the tip to construct the motor structure. After the motor has been formed, the flagellar filament, which functions as a helical propeller, is assembled. Precise recognition of the template structure by component proteins allows this highly ordered self-assembly process to proceed without error. The flagellar filament is made of 20,000 to 30,000 copies of flagellin polymerized into a helical tube structure. Flagellin molecules are transported through a long narrow central channel of the flagellum from the cell interior to the distal end of the flagellum, where they self-assemble in a helical manner by the help of a cap complex. The cap is pentameric complex made of HAP2 and has a pentagonal plate and five leg domains, whose flexible stepping movements accompanied by rotation of the whole cap is the key mechanism to promote the efficient self-assembly of flagellin molecules by preparing just one binding site of flagellin at a time and guiding the binding.

This article recently published in Accounts of Chemical Research discusses some key considerations for understanding how proteins bind in cellular machines, and offers a new approach to predicting binding. It provides some of the quantitative basis needed for putting irreducible complexity on a quantitative basis. Notably the authors seek to document the effect of mutations on reduced specificity of binding: "We have found that introducing mutations can significantly reduce specificity by introducing an additional binding mode." which reduction in specificity would be the first stage in the failure of a reducibly complex machine.

Worth reading both by those looking at the biochemistry and biology of protein machines and those pursuing the probability arguments of Intelligent Design.

Acc. Chem. Res., ASAP Article 10.1021 ar040204a S0001 4842(04)00204 3
Web Release Date: October 15, 2005
Copyright 2005 American Chemical Society
Mechanisms of Protein Assembly: Lessons from Minimalist Models
Yaakov Levy and Jose N. Onuchic
Center for Theoretical Biological Physics, Department of Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093

Received May 26, 2005

Abstract:
Many cellular functions rely on interactions among proteins and between proteins and nucleic acids. The limited success of binding predictions may suggest that the physical and chemical principles of protein binding have to be revisited to correctly capture the essence of protein recognition. In this Account, we discuss the power of reduced models to study the physics of protein assembly. Since energetic frustration is sufficiently small, native topology-based models, which correspond to perfectly unfrustrated energy landscapes, have shown that binding mechanisms are robust and governed primarily by the protein's native topology. These models impressively capture many of the binding characteristics found in experiments and highlight the fundamental role of flexibility in binding. The essential role of solvent molecules and electrostatic interactions in binding is also discussed. Despite the success of the minimally frustrated models to describe the dynamics and mechanisms of binding, the actual degree of frustration has to be explored to quantify the capacity of a protein to bind specifically to other proteins. We have found that introducing mutations can significantly reduce specificity by introducing an additional binding mode. Deciphering and quantifying the key ingredients for biological self-assembly is invaluable to reading out genomic sequences and understanding cellular interaction networks.

Introduction
The life of cells is orchestrated by a network of chemical reactions involving numerous proteins and nucleic acids and the transport of those molecules between cellular compartments. The remarkable efficiency of organizing these processes to yield a cellular function presents a major theoretical puzzle given the large number of molecular species and the crowded environment they inhabit. In the recent years, we have come to understand the assembly of the individual actors in this drama thanks to many cooperative efforts between experiments and theory. We now understand the main principles of folding kinetics[1,2] can often predict monomeric protein structure[3] and can even design novel protein structures.[4] However, knowing everything about isolated monomeric proteins does not give a complete understanding of function. Function requires change of structure and specific recognition to form large assemblies. These processes must be governed by the information stored in their sequences and structures. Furthermore, biomacromolecules are flexible with a rich repertoire of movements on various length and time scales. These motions are essential to determine the ability of a protein to bind different ligands at the same or different binding sites.[5,6] Deciphering the molecular and structural origins of high specificity as well as the catalytic promiscuity and multitasking of proteins is prerequisite for a quantitative understanding of the complexity and multidimensionality in genomes. This cooperation of many proteins and nucleic acids, which is largely "wireless", is quite intricate. Understanding the principles of biomolecular assembly in quantitative detail constitutes the basis for the molecular theory of biological networks.

Theoretical and computational studies of protein binding have concentrated on analyzing the structural and chemical properties of interfaces[7,8] as well as predicting the structure of the formed complexes and their binding affinity.[9,10] Understanding the organization of proteins into large complexes is required to understand their function and irreversible aggregation. The challenge of predicting the complex formed between pairs of proteins has been addressed for several years by docking two proteins using various models, which range from reduced models11[12] to atomistic ones[9] and include different flavors. Approaches to predict the structures of higher complexes, which are often defined as cellular machines, have been recently developed too. These approaches include, for example, combinatorial docking schemes[13] or fitting to cryo density maps at low resolution.[14] Some progress has been made in recent years in the performance of docking algorithms, yet their successes in predicting the structure of the protein complex are limited mainly to docking of the bound conformations of the complex subunits.

The inferiority of binding prediction to folding prediction is surprising because the conformational search required in binding processes of two folded proteins is smaller than that involved in protein folding. This shortcoming suggests that the physical and chemical principles of protein binding have to be revisited. The poor predictions of docking when using the conformations of the free subunits obviously indicates that protein flexibility is an important component in binding. Several docking approaches have introduced side-chain flexibility by using a rotamers library; however, it seems that backbone flexibility cannot be ignored.[15] It is likely, thus, that flexibility effects are still grossly underestimated as suggested from our recent association studies.[16-18] Solvent is also a critical component in protein association. While the protein cores are usually dry and contain a few water molecules, the interfaces in protein complexes are often very wet[19] (see Figure 1). Recently, it was found that a funneled potential for binding between proteins was obtained only upon solvation of assembly interfaces.[20] These observations provide a strong indication that water can be indispensable in protein assembly and undoubtedly in protein binding to DNA due to its highly charged surface.

This is from a Letter to Nature in the October 6, 2005 issue.

Nature 437, 862-865 (6 October 2005)

Microscopic artificial swimmers

Remi Dreyfus, Jean Baudry, Marcus L. Roper, Marc Fermigier, Howard A. Stone and Jerome Bibette

Abstract: Microorganisms such as bacteria and many eukaryotic cells propel themselves with hair-like structures known as flagella, which can exhibit a variety of structures and movement patterns. For example, bacterial flagella are helically shaped and driven at their bases by a reversible rotary engine, which rotates the attached flagellum to give a motion similar to that of a corkscrew. In contrast, eukaryotic cells use flagella that resemble elastic rods and exhibit a beating motion: internally generated stresses give rise to a series of bends that propagate towards the tip. In contrast to this variety of swimming strategies encountered in nature, a controlled swimming motion of artificial micrometre-sized structures has not yet been realized. Here we show that a linear chain of colloidal magnetic particles linked by DNA and attached to a red blood cell can act as a flexible artificial flagellum. The filament aligns with an external uniform magnetic field and is readily actuated by oscillating a transverse field. We find that the actuation induces a beating pattern that propels the structure, and that the external fields can be adjusted to control the velocity and the direction of motion.

Cell Biology International
Volume 28, Issue 11 , November 2004, Pages 729-739

Copyright © 2004 International Federation for Cell Biology Published by Elsevier Ltd.
Chance and necessity do not explain the origin of life

J.T. Trevors(a) and D.L. Abel(b)

(a)Laboratory of Microbial Technology, Department of Environmental Biology, Room 3220, Bovey Building, University of Guelph, Guelph, Ontario, Canada, N1G 2W1
(b)The Gene Emergence Project, The Origin-of-Life Foundation Inc., 113 Hedgewood Dr., Greenbelt, MD 20770-1610, USA

Received 8 April 2004; revised 19 May 2004; accepted 24 June 2004. Available online 17 November 2004.

Abstract
Where and how did the complex genetic instruction set programmed into DNA come into existence? The genetic set may have arisen elsewhere and was transported to the Earth. If not, it arose on the Earth, and became the genetic code in a previous lifeless, physical–chemical world. Even if RNA or DNA were inserted into a lifeless world, they would not contain any genetic instructions unless each nucleotide selection in the sequence was programmed for function. Even then, a predetermined communication system would have had to be in place for any message to be understood at the destination. Transcription and translation would not necessarily have been needed in an RNA world. Ribozymes could have accomplished some of the simpler functions of current protein enzymes. Templating of single RNA strands followed by retemplating back to a sense strand could have occurred. But this process does not explain the derivation of “sense” in any strand. “Sense” means algorithmic function achieved through sequences of certain decision-node switch-settings. These particular primary structures determine secondary and tertiary structures. Each sequence determines minimum-free-energy folding propensities, binding site specificity, and function. Minimal metabolism would be needed for cells to be capable of growth and division. All known metabolism is cybernetic – that is, it is programmatically and algorithmically organized and controlled.

Keywords: Cellular communication; Chance; Necessity; Genetic control; DNA; RNA; Evolution; Information theory; Life origin; Astrobiology; Panspermia