Showing papers by "United States Department of Energy published in 2008"

Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

Abstract: Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ancestry groups. To identify genetic variants contributing to differences in hepatic fat content, we carried out a genome-wide association scan of nonsynonymous sequence variations (n = 9,229) in a population comprising Hispanic, African American and European American individuals. An allele in PNPLA3 (rs738409[G], encoding I148M) was strongly associated with increased hepatic fat levels (P = 5.9 x 10(-10)) and with hepatic inflammation (P = 3.7 x 10(-4)). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was more than twofold higher in PNPLA3 rs738409[G] homozygotes than in noncarriers. Resequencing revealed another allele of PNPLA3 (rs6006460[T], encoding S453I) that was associated with lower hepatic fat content in African Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ancestry-related and inter-individual differences in hepatic fat content and susceptibility to NAFLD.

The Physcomitrella Genome Reveals Evolutionary Insights into the Conquest of Land by Plants

Abstract: We report the draft genome sequence of the model moss Physcomitrella patens and compare its features with those of flowering plants, from which it is separated by more than 400 million years, and unicellular aquatic algae. This comparison reveals genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments (e.g., flagellar arms); acquisition of genes for tolerating terrestrial stresses (e.g., variation in temperature and water availability); and the development of the auxin and abscisic acid signaling pathways for coordinating multicellular growth and dehydration response. The Physcomitrella genome provides a resource for phylogenetic inferences about gene function and for experimental analysis of plant processes through this plant's unique facility for reverse genetics.

The minimum information about a genome sequence (MIGS) specification.

Abstract: With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.

The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome.

Abstract: Following birth, the breast-fed infant gastrointestinal tract is rapidly colonized by a microbial consortium often dominated by bifidobacteria. Accordingly, the complete genome sequence of Bifidobacterium longum subsp. infantis ATCC15697 reflects a competitive nutrient-utilization strategy targeting milk-borne molecules which lack a nutritive value to the neonate. Several chromosomal loci reflect potential adaptation to the infant host including a 43 kbp cluster encoding catabolic genes, extracellular solute binding proteins and permeases predicted to be active on milk oligosaccharides. An examination of in vivo metabolism has detected the hallmarks of milk oligosaccharide utilization via the central fermentative pathway using metabolomic and proteomic approaches. Finally, conservation of gene clusters in multiple isolates corroborates the genomic mechanism underlying milk utilization for this infant-associated phylotype.

Designing adsorbents for CO2 capture from flue gas-hyperbranched aminosilicas capable of capturing CO2 reversibly.

Abstract: Carbon dioxide adsorption from a simulated flue gas stream was successfully performed with a hyperbranched aminosilica (HAS) material. The HAS was synthesized by a one-step reaction, spontaneous aziridine ring-opening polymerization off of surface silanols, to form a 32 wt % organic/inorganic hybrid material. The adsorption measurements were performed in a fixed-bed flow reactor using humidified CO2. The advantage of this adsorbent over previously reported adsorbents is the stability of the organic groups covalently bound to the silica support compared to those made by physisorbed methods. Furthermore, a large CO2 capacity (∼3 mmol CO2/g adsorbent) associated with the high loading of amines was observed.

Dicer, Drosha, and outcomes in patients with ovarian cancer

Abstract: BACKGROUND We studied Dicer and Drosha, components of the RNA-interference machinery, in ovarian cancer. METHODS We measured messenger RNA (mRNA) levels of Dicer and Drosha in specimens of invasive epithelial ovarian cancer from 111 patients, using a quantitative reverse-transcriptase-polymerase-chain-reaction assay, and compared the results with clinical outcomes. Validation was performed with the use of published microarray data from cohorts of patients with ovarian, breast, and lung cancer. Mutational analyses of genomic DNA from the Dicer and Drosha genes were performed in a subgroup of ovarian-cancer specimens. Dicer-dependent functional assays were performed by means of in vitro transfection with small interfering RNA (siRNA) and short hairpin RNA (shRNA). RESULTS Levels of Dicer and Drosha mRNA correlated with the levels of expression of the corresponding protein and were decreased in 60% and 51% of ovarian-cancer specimens, respectively. Low Dicer expression was significantly associated with advanced tumor stage (P=0.007), and low Drosha expression with suboptimal surgical cytoreduction (P=0.02). Cancer specimens with both high Dicer expression and high Drosha expression were associated with increased median survival (>11 years, vs. 2.66 years for other subgroups; P<0.001). We found three independent predictors of reduced disease-specific survival in multivariate analyses: low Dicer expression (hazard ratio, 2.10; P=0.02), high-grade histologic features (hazard ratio, 2.46; P=0.03), and poor response to chemotherapy (hazard ratio, 3.95; P<0.001). Poor clinical outcomes among patients with low Dicer expression were validated in additional cohorts of patients. Rare missense mutations were found in the Dicer and Drosha genes, but their presence or absence did not correlate with the level of expression. Functional assays indicated that gene silencing with shRNA, but not siRNA, may be impaired in cells with low Dicer expression. CONCLUSIONS Our findings indicate that levels of Dicer and Drosha mRNA in ovarian-cancer cells have associations with outcomes in patients with ovarian cancer.

Toward an online repository of Standard Operating Procedures (SOPs) for (meta)genomic annotation.

Abstract: The methodologies used to generate genome and metagenome annotations are diverse and vary between groups and laboratories. Descriptions of the annotation process are helpful in interpreting genome annotation data. Some groups have produced Standard Operating Procedures (SOPs) that describe the annotation process, but standards are lacking for structure and content of these descriptions. In addition, there is no central repository to store and disseminate procedures and protocols for genome annotation. We highlight the importance of SOPs for genome annotation and endorse an online repository of SOPs.

The amphioxus genome illuminates vertebrate origins and cephalochordate biology

Abstract: Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates

Environmental genomics reveals a single-species ecosystem deep within Earth.

Abstract: DNA from low-biodiversity fracture water collected at 2.8-kilometer depth in a South African gold mine was sequenced and assembled into a single, complete genome. This bacterium, Candidatus Desulforudis audaxviator, composes >99.9% of the microorganisms inhabiting the fluid phase of this particular fracture. Its genome indicates a motile, sporulating, sulfate-reducing, chemoautotrophic thermophile that can fix its own nitrogen and carbon by using machinery shared with archaea. Candidatus Desulforudis audaxviator is capable of an independent life-style well suited to long-term isolation from the photosphere deep within Earth's crust and offers an example of a natural ecosystem that appears to have its biological component entirely encoded within a single genome.

Filtered two‐fluid models for fluidized gas‐particle suspensions

Abstract: Starting from a kinetic theory based two-fluid model for gas-particle flows, we first construct filtered two-fluid model equations that average over small scale inhomogeneities that we do not wish to resolve in numerical simulations. We then outline a procedure to extract constitutive models for these filtered two-fluid models through highly resolved simulations of the kinetic theory based model equations in periodic domains. Two- and three-dimensional simulations show that the closure relations for the filtered two-fluid models manifest a definite and systematic dependence on the filter size. Linear stability analysis of the filtered two-fluid model equations reveals that filtering does indeed remove small scale structures that are afforded by the microscopic twofluid model. 2008 American Institute of Chemical Engineers AIChE J, 54: 1431–1448, 2008

Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans

Abstract: The relative activity of lipoprotein lipase (LPL) in different tissues controls the partitioning of lipoprotein-derived fatty acids between sites of fat storage (adipose tissue) and oxidation (heart and skeletal muscle). Here we used a reverse genetic strategy to test the hypothesis that 4 angiopoietin-like proteins (ANGPTL3, -4, -5, and -6) play key roles in triglyceride (TG) metabolism in humans. We re-sequenced the coding regions of the genes encoding these proteins and identified multiple rare nonsynonymous (NS) sequence variations that were associated with low plasma TG levels but not with other metabolic phenotypes. Functional studies revealed that all mutant alleles of ANGPTL3 and ANGPTL4 that were associated with low plasma TG levels interfered either with the synthesis or secretion of the protein or with the ability of the ANGPTL protein to inhibit LPL. A total of 1% of the Dallas Heart Study population and 4% of those participants with a plasma TG in the lowest quartile had a rare loss-of-function mutation in ANGPTL3, ANGPTL4, or ANGPTL5. Thus, ANGPTL3, ANGPTL4, and ANGPTL5, but not ANGPTL6, play nonredundant roles in TG metabolism, and multiple alleles at these loci cumulatively contribute to variability in plasma TG levels in humans.

Human-specific gain of function in a developmental enhancer.

Abstract: Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.

Ultraconservation identifies a small subset of extremely constrained developmental enhancers

Abstract: Extended perfect human-rodent sequence identity of at least 200 base pairs (ultraconservation) is potentially indicative of evolutionary or functional uniqueness. We used a transgenic mouse assay to compare the embryonic enhancer activity of 231 noncoding ultraconserved human genome regions with that of 206 extremely conserved regions lacking ultraconservation. Developmental enhancers were equally prevalent in both populations, suggesting instead that ultraconservation identifies a small, functionally indistinct subset of similarly constrained cis-regulatory elements.

A photoactive carotenoid protein acting as light intensity sensor

Abstract: Intense sunlight is dangerous for photosynthetic organisms. Cyanobacteria, like plants, protect themselves from light-induced stress by dissipating excess absorbed energy as heat. Recently, it was discovered that a soluble orange carotenoid protein, the OCP, is essential for this photoprotective mechanism. Here we show that the OCP is also a member of the family of photoactive proteins; it is a unique example of a photoactive protein containing a carotenoid as the photoresponsive chromophore. Upon illumination with blue-green light, the OCP undergoes a reversible transformation from its dark stable orange form to a red “active” form. The red form is essential for the induction of the photoprotective mechanism. The illumination induces structural changes affecting both the carotenoid and the protein. Thus, the OCP is a photoactive protein that senses light intensity and triggers photoprotection.

Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers

Abstract: We have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the number of genes altered by major copy number changes, deletion of all copies or amplification to at least 12 copies per cell, averaged 17 per tumor. We have integrated these data with previous mutation analyses of the Reference Sequence genes in these same tumor types and have identified genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations included those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that could prove useful for cancer diagnosis and therapy.

Rapid whole-genome mutational profiling using next-generation sequencing technologies

Abstract: Forward genetic mutational studies, adaptive evolution, and phenotypic screening are powerful tools for creating new variant organisms with desirable traits. However, mutations generated in the process cannot be easily identified with traditional genetic tools. We show that new high-throughput, massively parallel sequencing technologies can completely and accurately characterize a mutant genome relative to a previously sequenced parental (reference) strain. We studied a mutant strain of Pichia stipitis, a yeast capable of converting xylose to ethanol. This unusually efficient mutant strain was developed through repeated rounds of chemical mutagenesis, strain selection, transformation, and genetic manipulation over a period of seven years. We resequenced this strain on three different sequencing platforms. Surprisingly, we found fewer than a dozen mutations in open reading frames. All three sequencing technologies were able to identify each single nucleotide mutation given at least 10–15-fold nominal sequence coverage. Our results show that detecting mutations in evolved and engineered organisms is rapid and cost-effective at the whole-genome level using new sequencing technologies. Identification of specific mutations in strains with altered phenotypes will add insight into specific gene functions and guide further metabolic engineering efforts.

Genesis and Expansion of Metazoan Transcription Factor Gene Classes

Abstract: We know little about the genomic events that led to the advent of a multicellular grade of organization in animals, one of the most dramatic transitions in evolution. Metazoan multicellularity is correlated with the evolution of embryogenesis, which presumably was underpinned by a gene regulatory network reliant on the differential activation of signaling pathways and transcription factors. Many transcription factor genes that play critical roles in bilaterian development largely appear to have evolved before the divergence of cnidarian and bilaterian lineages. In contrast, sponges seem to have a more limited suite of transcription factors, suggesting that the developmental regulatory gene repertoire changed markedly during early metazoan evolution. Using whole-genome information from the sponge Amphimedon queenslandica, a range of eumetazoans, and the choanoflagellate Monosiga brevicollis, we investigate the genesis and expansion of homeobox, Sox, T-box, and Fox transcription factor genes. Comparative analyses reveal that novel transcription factor domains (such as Paired, POU, and T-box) arose very early in metazoan evolution, prior to the separation of extant metazoan phyla but after the divergence of choanoflagellate and metazoan lineages. Phylogenetic analyses indicate that transcription factor classes then gradually expanded at the base of Metazoa before the bilaterian radiation, with each class following a different evolutionary trajectory. Based on the limited number of transcription factors in the Amphimedon genome, we infer that the genome of the metazoan last common ancestor included fewer gene members in each class than are present in extant eumetazoans. Transcription factor orthologues present in sponge, cnidarian, and bilaterian genomes may represent part of the core metazoan regulatory network underlying the origin of animal development and multicellularity.

Structurally Ordered Mesoporous Carbon Nanoparticles as Transmembrane Delivery Vehicle in Human Cancer Cells

Abstract: A structurally ordered, CMK-1 type mesoporous carbon nanoparticle (MCN) material was successfully synthesized by using a MCM-48 type mesoporous silica nanoparticle as template. The structure of MCN was analyzed by a series of different techniques, including the scanning and transmission electron microscopy, powder X-ray diffraction, and N2 sorption analysis. To the best of our knowledge, no study has been reported prior to our investigation on the utilization of these structurally ordered mesoporous carbon nanoparticles for the delivery of membrane impermeable chemical agents inside of eukaryotic cells. The cellular uptake efficiency and biocompatibility of MCN with human cervical cancer cells (HeLa) were investigated. Our results show that the inhibitory concentration (IC50) value of MCN is very high (>50 microg/mL per million cells) indicating that MCN is fairly biocompatible in vitro. Also, a membrane impermeable fluorescence dye, Fura-2, was loaded to the mesoporous matrix of MCN. We demonstrated that the MCN material could indeed serve as a transmembrane carrier for delivering Fura-2 through the cell membrane to release these molecules inside of live HeLa cells. We envision that further developments of this MCN material will lead to a new generation of nanodevices for transmembrane delivery and intracellular release applications.

A constant-time kinetic Monte Carlo algorithm for simulation of large biochemical reaction networks

Abstract: The time evolution of species concentrations in biochemical reaction networks is often modeled using the stochastic simulation algorithm SSAGillespie, J. Phys. Chem. 81, 2340 1977. The computational cost of the original SSA scaled linearly with the number of reactions in the network. Gibson and Bruck developed a logarithmic scaling version of the SSA which uses a priority queue or binary tree for more efficient reaction selection Gibson and Bruck, J. Phys. Chem. A 104, 1876 2000. More generally, this problem is one of dynamic discrete random variate generation which finds many uses in kinetic Monte Carlo and discrete event simulation. We present here a constant-time algorithm, whose cost is independent of the number of reactions, enabled by a slightly more complex underlying data structure. While applicable to kinetic Monte Carlo simulations in general, we describe the algorithm in the context of biochemical simulations and demonstrate its competitive performance on small- and medium-size networks, as well as its superior constant-time performance on very large networks, which are becoming necessary to represent the increasing complexity of biochemical data for pathways that mediate cell function. © 2008 American Institute of Physics. DOI: 10.1063/1.2919546

Rate of CO2 attack on hydrated Class H well cement under geologic sequestration conditions.

Abstract: Experiments were conducted to study the degradation of hardened cement paste due to exposure to CO2 and brine under geologic sequestration conditions (T = 50 °C and 30.3 MPa). The goal was to determine the rate of reaction of hydrated cement exposed to supercritical CO2 and to CO2-saturated brine to assess the potential impact of degradation in existing wells on CO2 storage integrity. Two different forms of chemical alteration were observed. The supercritical CO2 alteration of cement was similar in process to cement in contact with atmospheric CO2 (ordinary carbonation), while alteration of cement exposed to CO2-saturated brine was typical of acid attack on cement. Extrapolation of the hydrated cement alteration rate measured for 1 year indicates a penetration depth range of 1.00 ± 0.07 mm for the CO2-saturated brine and 1.68 ± 0.24 mm for the supercritical CO2 after 30 years. These penetration depths are consistent with observations of field samples from an enhanced oil recovery site after 30 years of ex...

Modelling and control of variable-speed multi-pole permanent magnet synchronous generator wind turbine

Abstract: Emphasis of this article is on variable-speed pitch-controlled wind turbines with multi-pole permanent magnet synchronous generator (PMSG) and on their extremely soft drive-train shafts. A model and a control strategy for a full back-to-back converter wind turbine with multi-pole PMSG are described. The model comprises submodels of the aerodynamic rotor, the drive-train by a two-mass model, the permanent magnet generator and the full-scale converter system. The control strategy, which embraces both the wind turbine control itself and the control of the full-scale converter, has tasks to control independently the active and reactive powers, to assist the power system and to ensure a stable normal operation of the wind turbine itself. A multi-pole PMSG connected to the grid through a full-scale converter has no inherent damping, and therefore, such configuration can become practically unstable, if no damping by means of external measures is applied. In this work, the frequency converter is designed to damp actively the drive-train oscillations, thus ensuring stable operation. The dynamic performance of the presented model and control strategy is assessed and emphasized in normal operation conditions by means of simulations in the power system simulation tool DIgSILENT. Copyright © 2008 John Wiley & Sons, Ltd.

Linking an economic model for European agriculture with a mechanistic model to estimate nitrogen and carbon losses from arable soils in Europe

Abstract: . A comprehensive assessment of policy impact on greenhouse gas (GHG) emissions from agricultural soils requires careful consideration of both socio-economic aspects and the environmental heterogeneity of the landscape. We developed a modelling framework that links the large-scale economic model for agriculture CAPRI (Common Agricultural Policy Regional Impact assessment) with the biogeochemistry model DNDC (DeNitrification DeComposition) to simulate GHG fluxes, carbon stock changes and the nitrogen budget of agricultural soils in Europe. The framework allows the ex-ante simulation of agricultural or agri-environmental policy impacts on a wide range of environmental problems such as climate change (GHG emissions), air pollution and groundwater pollution. Those environmental impacts can be analyzed in the context of economic and social indicators as calculated by the economic model. The methodology consists of four steps: (i) definition of appropriate calculation units that can be considered as homogeneous in terms of economic behaviour and environmental response; (ii) downscaling of regional agricultural statistics and farm management information from a CAPRI simulation run into the spatial calculation units; (iii) designing environmental model scenarios and model runs; and finally (iv) aggregating results for interpretation. We show the first results of the nitrogen budget in croplands in fourteen countries of the European Union and discuss possibilities to improve the detailed assessment of nitrogen and carbon fluxes from European arable soils.

Social contact networks for the spread of pandemic influenza in children and teenagers.

Abstract: Influenza is a viral infection that primarily spreads via fluid droplets from an infected person's coughs and sneezes to others nearby. Social contact networks and the way people interact within them are thus important to its spread. We developed a method to characterize the social contact network for the potential transmission of influenza and then applied the method to school aged children and teenagers. Surveys were administered to students in an elementary, middle and high-school in the United States. The social contact network of a person was conceptualized as a set of groups to which they belong (e.g., households, classes, clubs) each composed of a sub-network of primary links representing the individuals within each group that they contact. The size of the group, number of primary links, time spent in the group, and level of contact along each primary link (near, talking, touching, or kissing) were characterized. Public activities done by groups venturing into the community where random contacts occur (e.g., friends viewing a movie) also were characterized. Students, groups and public activities were highly heterogeneous. Groups with high potential for the transmission of influenza were households, school classes, friends, and sports; households decreased and friends and sports increased in importance with grade level. Individual public activity events (such as dances) were also important but lost their importance when averaged over time. Random contacts, primarily in school passing periods, were numerous but had much lower transmission potential compared to those with primary links within groups. Students are highly assortative, interacting mainly within age class. A small number of individual students are identified as likely "super-spreaders". High-school students may form the local transmission backbone of the next pandemic. Closing schools and keeping students at home during a pandemic would remove the transmission potential within these ages and could be effective at thwarting its spread within a community. Social contact networks characterized as groups and public activities with the time, level of contact and primary links within each, yields a comprehensive view, which if extended to all ages, would allow design of effective community containment for pandemic influenza.

Assembly of viral metagenomes from yellowstone hot springs.

Abstract: Thermophilic viruses were reported decades ago; however, knowledge of their diversity, biology, and ecological impact is limited. Previous research on thermophilic viruses focused on cultivated strains. This study examined metagenomic profiles of viruses directly isolated from two mildly alkaline hot springs, Bear Paw (74°C) and Octopus (93°C). Using a new method for constructing libraries from picograms of DNA, nearly 30 Mb of viral DNA sequence was determined. In contrast to previous studies, sequences were assembled at 50% and 95% identity, creating composite contigs up to 35 kb and facilitating analysis of the inherent heterogeneity in the populations. Lowering the assembly identity reduced the estimated number of viral types from 1,440 and 1,310 to 548 and 283, respectively. Surprisingly, the diversity of viral species in these springs approaches that in moderate-temperature environments. While most known thermophilic viruses have a chronic, nonlytic infection lifestyle, analysis of coding sequences suggests lytic viruses are more common in geothermal environments than previously thought. The 50% assembly included one contig with high similarity and perfect synteny to nine genes from Pyrobaculum spherical virus (PSV). In fact, nearly all the genes of the 28-kb genome of PSV have apparent homologs in the metagenomes. Similarities to thermoacidophilic viruses isolated on other continents were limited to specific open reading frames but were equally strong. Nearly 25% of the reads showed significant similarity between the hot springs, suggesting a common subterranean source. To our knowledge, this is the first application of metagenomics to viruses of geothermal origin.