Category Archives: Genome

Washington, June 13 (ANI): A team of Spanish researchers, coordinated by the Spanish National Research Council (CSIC), has begun sequencing the genome of the global deep ocean.

They are using more than 2,000 samples of microorganisms collected in the Atlantic, Indian and Pacific Oceans during the Malaspina Expedition. This collection of marine microbial genomic, the first in the world on a global scale, will provide new clues about a reservoir of biodiversity yet to explore, considering that it could imply the discovery of tens of millions of new genes in the coming years.

The works of sequencing (framed in the Malaspinomics project) focus on the viruses, bacteria and protists that inhabit the ocean to 4,000 meters deep.

Most of the biomass of marine organisms is composed of microorganism. Of these, a 72 percent inhabit the dark ocean, from 200 meters deep. However, so far, the DNA or RNA sequencing had been almost exclusively limited to the ocean surface waters.

Malaspinomics preliminary results reveal a wealth of unknown species of microorganisms in the deep ocean, characterized by an intense biological activity. Specifically, 60 percent of the bacterial species of the deep ocean detected by massive sequencing techniques are unknown.

Carlos Duarte, CSIC researcher and coordinator of Malaspina Expedition, asserted: "Malaspinomics means a leap forward because, for the first time, we are analyzing samples from the deep ocean, covering the great oceans. The new protocols of sequencing and analysis allow us to extract quite more information than in previous studies, which were limited to specific regions or surface waters, to an unprecedented level of resolution".

Researchers have already detected some bacteria, which are capable of degrading highly toxic compounds that have gradually gathered in the seabed.

Analysis are being conducted by a team that includes researchers from the Institute of Marine Sciences (CSIC), the Mediterranean Institute for Advanced Studies -joint centre of CSIC and the University of the Balearic Islands (UIB)- and the National Genome Analysis Centre of Barcelona (CNAG).

They also count on the collaboration of MareNostrum -National Supercomputing Centre (BSC) in Barcelona-, the Joint Genome Institute (USA) and the European Molecular Biology Laboratory (Germany). (ANI)

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Genome of global deep ocean being sequenced

June 13, 2013

Image Caption: Emiliania huxleyi's shapes are as varied as the ocean environments it lives in. Credit: Nature

redOrbit Staff & Wire Reports Your Universe Online

An international team of researchers has sequenced the genome of Emiliania huxleyi, a species of single-celled photosynthetic marine algae that they say is responsible for removing carbon dioxide from the air, supplying the oxygen we breath, and even forming the basis of marine food chains.

The results of their work has just been published in the journal Nature and helps explain the tremendous adaptive potential and global distribution of this algae, which is smaller than a speck of dust and contains a shield of thin calcified platelets resembling the outside of a soccer ball.

A team of 75 researchers from a dozen different countries spent seven years mapping the genome, and found a set of core genes that have mixed with a separate set of variable genes. The authors reported that genetic diversity allows E. huxleyi (Ehux for short) to adapt to different environments, as part of its gene pool is dependent upon its geographic location and living conditions. It is the first algae in which scientists have detected this unique characteristic.

The Ehux genome is incredibly variable, said study co-author Dr. Uwe John and biologist with the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI). For example, if the genetic information of two humans is compared, an agreement of about 99 per cent is found. However, if, for example, we take two Ehux strains from different ocean regions, we find a degree of similarity of only 70 or 80 per cent. The rest of the genome differs.

This means that all of the algae possess a certain basic set of genes, the core genome, which is supplemented by different genes, i.e. is interchangeable to a certain extent, depending on the habitat of the algae, he continued. In the scientific world, we call this phenomenon pan-genome, which was only known from bacteria until we conducted our study. We have now demonstrated the pan-genome in a calcified alga for the first time.

Dr. John and colleagues from the Department of Energy Joint Genome Institute (DOE JGI) sequenced the Ehux genome and compared it with the genetic information from other algal isolates, reporting their results in the June 12 edition of Nature. The strain sequenced by the researchers was isolated from the South Pacific and is the first reference genome for coccolithophores.

The project wound up taking the scientists longer to complete than originally predicted because of the complexity and size of the Ehux genome. They originally believed that it was an estimated 30 million bases, but the genome wound up being more than four times that size approximately 141 million bases. Sequencing efforts of Ehux, which is part of the third most abundant group of phytoplankton, was first proposed by researchers back in 2002.

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Bizarre Ehux Algae Adapts To Environment With Variable Genome

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Fundamental uncertainties exist regarding the physiology and ecology of E. huxleyi, and the relationships between different morphotypes (Fig. 1a). To investigate its gene repertoire and physiological capacity, we sequenced the diploid genome of CCMP1516 using the Sanger shotgun approach. The haploid genome is estimated to be 141.7megabases (Mb) and 97% complete on the basis of conserved eukaryotic single-copy genes5, 6 (Supplementary Table 1, Supplementary Data 7 and Supplementary Information 1.11.4). It is dominated by repetitive elements, constituting >64% of the sequence, much greater than seen for sequenced diatoms (Fig. 2 and Supplementary Information 2.10). Of the 30,569 protein-coding genes predicted93% of which have transcriptomic support (expressed sequence tag or RNA-seq) (Supplementary Information 1.51.7, 2.12.2 and Supplementary Data 13)we identified expansions in gene families specific to iron/macromolecular transport, post-translational modification, cytoskeletal development and signal transduction relative to other sequenced eukaryotic algae (Supplementary Information 2.3).

a, E. huxleyi has five well-characterized calcification morphotypes and an overcalcified state1. b, Cladogram showing the distinct branch occupied by the haptophyte lineage on the basis of RAxML analysis of concatenated, nuclear-encoded proteins after addition of homologues from CCMP1516 and a pico-prymnesiophyte-targeted metagenome8. Lineages with algal taxa are indicated (symbol). Filled circles represent nodes with70% bootstrap support. The tree is rooted for display purposes only.

Structural composition of genomes from CCMP1516 and the diatom P. tricornutum. Grey-shaded regions of each class depict proportions of tandem repeats and low-complexity regions. The grey vertical box contains only tandem repeats and low-complexity sequence. Pie charts indicate the proportion of non-repeated (white) and repeated or low-complexity (black) sequences in each haploid genome.

The E. huxleyi genome provides a crucial reference point for evolutionary, cellular and physiological studies because haptophytes represent a distinct branch on the eukaryotic tree of life (Fig. 1b). Consistent with other published analyses7, conserved marker genes demonstrate the haptophytes branch as a sister clade to heterokonts, alveolates and rhizarians. However, as a lineage possessing secondary plastids, the evolutionary history of haptophyte genomes may be more complex8 than that suggested by a single concatenated analysis. Thus, individual gene phylogenies were constructed using clusters of orthologous proteins (1,563) identified by comparative analysis of E. huxleyi and at least 9 of 48 taxa sampled from across eukaryotes (Supplementary Information 2.4). E. huxleyi was monophyletic, with heterokonts in 2833% of the resolved trees and the green lineage (green algae and plants) in 1114%. Less frequent relationships were also observed, presumably reflecting a mosaic genome8 with contributions from the host lineage, the eukaryotic endosymbiont, and possibly horizontal gene transfer (Supplementary Fig. 1 and Supplementary Data 4).

Coccolithophores produce the anti-stress osmolyte dimethylsulphoniopropionate (DMSP), which can be demethylated to produce methylmercaptopropionate and/or cleaved by some organisms, such as E. huxleyi, to produce the predominant natural source of atmospheric sulphur, dimethylsulphide. Although the gene encoding the DmdA protein, which catalyses the initial demethylation of DMSP, was not detected in the genome, genes that produce sulphur and carbon intermediates and function in later stages of DMSP degradation were identified9. Also present is an intron-containing, but otherwise bacterial dddD-like, gene encoding an acetyl-coenzyme A (acetyl-CoA) transferase proposed to add CoA to DMSP before cleavage9 (Supplementary Table 2). These data will facilitate molecular approaches for probing DMSP biogeochemistry and the environmental importance of sulphur production and biotransformations.

E. huxleyi synthesizes unusual lipids that are used as nutritional/feedstock supplements, polymer precursors and petrochemical replacements. Two functionally redundant pathways for the synthesis of omega-3 polyunsaturated eicosapentaenoic and docosahexaenoic fatty acids were partially characterized10 (Supplementary Table 3). Pathway analysis indicates that E. huxleyi sphingolipids are primarily glucosylceramides, often with an unusual C9 methyl branch (Supplementary Table 3) found only in fungi and some animals11. Genes for two zinc-containing quinone reductases, involved in reduction of alkenone ,-double bonds used in paleotemperature reconstructions and proposed biofuels, were also identified12, 13.

Coccoliths have precise nanoscale architecture and unique light-scattering properties of interest to material and optoelectronic scientists. Carbonic anhydrase is associated with biomineralization in other organisms14 and accelerates bicarbonate formation. The 15 E. huxleyi carbonic anhydrase isozymes and genes involved in calcium and carbon transport, H+ efflux, cytoskeleton organization and polysaccharide modulation (Supplementary Table 4) represent targets for resolving molecular mechanisms governing coccolith formation, and will aid in predicting response patterns to anthropogenic CO2 increases and ocean acidification.

The global distribution of E. huxleyi (for example, Fig. 3a, c) and its capacity for bloom formation under different physiochemical parameters are puzzling. To investigate the potential influence of genome variation in this ecological dynamic, three E. huxleyi isolates (92A, EH2 and Van556) from different oceanic regions were deeply sequenced (265352-fold coverage) (Fig. 3a, c, Supplementary Tables 57 and Supplementary Information 2.6). Two approaches were used to compare genomes. First, sequence reads were assembled and contigs aligned to the CCMP1516 reference genome using Standard Nucleotide BLAST (BLASTn; Supplementary Information 2.6.1). Although these isolates show >98% 18S ribosomal RNA (rRNA) identity, only 5477% of their contigs showed similarity to CCMP1516. 71Mb of the remaining contigs were shared between at least two deeply sequenced strains. 840Mb appeared to be isolate specific, as did 27Mb of CCMP1516. Flow cytometric genome-size estimates also showed heterogeneity across isolates, with haploid genome sizes ranging from 99 to 133Mb (Supplementary Information 2.5, 2.6.1 and Supplementary Table 5). These findings indicated considerable intraspecific variation.

a, Isolation locations shown over the averaged Reynolds monthly sea-surface temperature (SST) climatology (19852007). b, tBLASTn homology search results using predicted CCMP1516 proteins against assemblies from other strains. Bars are coloured according to the number of gene products and nucleotide per cent identity. c, Best Bayesian topology, where node values indicate posterior probability/maximum-likelihood bootstrap support. Haploid genome sizes (in Mb) are provided in brackets (with ND indicating not determined), and shaded boxes denote robust clades of geographically dispersed strains. The variable distribution of nitrite reductase (NirS) and plastocyanin (PetE) is shown.

To examine potential variations in gene content further, sequence reads were directly mapped to the CCMP1516 genome. Of the 30,569 predicted genes in CCMP1516, between 1,373 and 2,012 different genes were not found in 92A, Van556 and EH2 (cumulatively 5,218, or 17% of CCMP1516 genes), and 364 appeared to be missing from all three. These findings cannot be explained by poor coverage or sequencing bias alone. Of 458 highly conserved eukaryotic genes from the CEGMA set5, 9597% were identified in the isolates, indicating nearly complete genome sequences (Supplementary Data 7). Together, de novo assemblies and direct mapping to CCMP1516 indicate that the pan genome of E. huxleyi represents a rapidly changing repository of genetic information with genomic fluidity estimated to be10%15 (on the basis of CCMP1516 gene content).

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Pan genome of the phytoplankton Emiliania underpins its global distribution

Issue of Trust - Are Vaccines Changing the Human Genome - 5-26-13
The most profound question regarding vaccines: are they changing the human genome? There is evidence that they can and do affect DNA, and as always, the precautionary principle should rule.

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By Jack Torry

The Columbus Dispatch Wednesday June 12, 2013 6:12 AM

WASHINGTON A new Battelle study shows that the federal governments efforts to finance research for the Human Genome Project have had nearly a $1 trillion impact on the U.S. economy during the past 25 years.

The report, scheduled to be released today by United for Medical Research at a briefing on Capitol Hill, delivers a powerful argument for federal research dollars. It claims that $14.5 billion in federal research dollars from 1988 through 2012 helped create more than 53,000 jobs in the genome field, boosted personal income by $293 billion and helped expand the nations output by $965 billion.

As the largest single undertaking in the history of life sciences, the Human Genome Project has paid back extraordinary dividends on the U.S. governments investment, Carrie Wolinetz, president of United for Medical Research, said in a statement. This report illustrates the vital role that key federal research funding plays in growing the U.S. economy, creating new industries and innovative technologies and producing the diagnostics and treatments that can save lives.

United for Medical Research is a coalition of research institutions across the country. Francis Collins, director of the National Institutes of Health, will be among the speakers at todays briefing.

Federal research dollars for the genome project date to 1987 when the Reagan administration first proposed the idea in its budget. There are roughly 20,000 genes in human beings, and scientists believe that studying these genes will demonstrate what causes disease.

jtorry@dispatch.com

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Genome project has been worth $1 trillion, Battelle says

Public release date: 12-Jun-2013 [ | E-mail | Share ]

Contact: David Gilbert degilbert@lbl.gov 925-296-5643 DOE/Joint Genome Institute

To World War II soldiers, "The White Cliffs of Dover" was a morale-boosting song that lifted spirits in dark times. To geographers, the white cliffs mark the point at which England is closest to continental Europe. To scientists, the white cliffs are towering structures made of the chalky, white shells that envelop the single-celled photosynthetic alga known as Emiliania huxleyi. "Ehux" is a coccolithophore, with an exoskeleton made of calcium carbonate. Even though the process by which the alga's "armor" forms releases carbon dioxide, Ehux can trap as much as 20 percent of organic carbon, derived from CO2, in some marine ecosystems.

Ehux and its brethren are the basis of most ocean food chains. Phytoplankton biomass exceeds that of all marine animals combined. Activities of Ehux and some other phytoplankton such as diatoms influence climate processes, such as lowering ocean temperatures by reflecting sunlight and through carbon metabolism. Its versatility in either contributing to primary production of organic compounds from carbon dioxide or adding to CO2 emissions makes Ehux a critical player in the marine carbon cycle. Sequenced by the Department of Energy Joint Genome Institute (DOE JGI), the Ehux genome was compared with sequences from other algal isolates and the results reported in the June 12 edition of Nature.

"Carbon dioxide is fixed during photosynthesis and calcification," said Betsy Read, a professor of biological sciences at California State University, San Marcos who led the large international consortium of 75 researchers from a dozen nations exploring Ehux and the first author of this paper. "It is also released during the process of calcification, but we do not know how this release balances with the amount of CO2 that is buried when Ehux sinks to the bottom of the ocean. This is an important yet unresolved question."

Part of the third most abundant group of phytoplankton, behind the diatoms and dinoflagellates, the Ehux strain sequenced by the DOE JGI was isolated from the South Pacific and is the first reference genome for coccolithophores. The project took longer than expected to complete due to the complexities and size of the Ehux genome. Originally estimated to be about 30 million bases, closer to a diatom, but the genome ended up being closer to 141 million bases. Starting with an individual investigator working with the DOE JGI for over ten years, the team forged a strong community of users to bring the project to completion.

"Because of the size and inherent complexities, the genome become known as 'The Beast' and without the epic persistence and unwavering commitment from the DOE JGI, the project would not have been completed," said Read, who proposed the sequencing of Ehux back in 2002.

With the advent of next generation sequencing technologies the team was able to conduct a comparison of 13 Ehux strains revealing the first ever algal 'pan-genome." Ehux doesn't exist as a clearly defined "species" with a uniform genome, but as a more diffuse community of genomesa "pan-genome"with different individuals possessing a shared "core" of genes, but supplemented by different gene sets thought to be useful in dealing with the particular challenges of its local environment.

"Ehux thrives in a broad range of physiochemical conditions in the ocean," said Igor Grigoriev, the paper's senior author, whose team from the DOE JGI led the genome annotation and analysis. "It's a complex genome, with lots of genes and repeats, the first reference for haptophytes and fills another gap in the Eukaryotic Tree of Life. It is amazing that while you need a microscope in order to see this elegantly sculptured microbe, you can see from outer space the light reflected from large areas of ocean during Ehux blooms."

The team found variability in the Ehux genome that helps explain the alga's ability to thrive in oceans from the equator to the subarctic and cause algal blooms in the spring and summer that can cover several hundred thousand square kilometers.

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Chalking up a marine blooming alga: Genome fills a gap in the tree of life

In his state of the union address this year, President Obama cited a study that estimated that taxpayers got a whopping $796 billion return from the $3.8 billion investment in sequencing the human genome. That larger than life number was laid out as an important reason to invest in basic science.

Now, an update to the report has been issued, finding the economic benefits of the governments investment in the field over a longer time frame, between 1988 and 2012, were even more vasta $1 trillion return.

The initial analysis raised some criticism and skepticism from economists due to issues with the methodology, and the new report seems destined to do the same.

How can they do this with a straight face? Julia Lane, an economist for the American Institutes for Research, said. If it was indeed a trillion dollar impact, then why are they doing anything except investing in the human genome project?

Lane said some of the calculations done in the new analysis are standard and reasonable. But what the report has also done, she said, is attribute every economic activity that has any association with the genome to the initial investment by the NIH.

The report was funded by United for Medical Research, an organization that represents research institutions, health advocates, and industry, and a contribution from Life Technologies Corp. Life Technologies is a company that makes genome sequencing technologies, and many of the groups represented by United for Medical Research have benefitted from the governments investment in the genome.

This report illustrates the vital role that key federal research funding plays in growing the U.S. economy, creating new industries and innovative technologies and producing diagnostics and treatments that can save lives, Carrie Wolinetz, president of United for Medical Research, said in a press release.

Dr. Jerome P. Kassirer, a former editor of the New England Journal of Medicine who has been vocal about conflicts of interest in medicine, said in an interview that although he does not doubt that the human genome project has had major economic repercussions, he does not know what to make of the reports findings.

I would never be satisfied with something as sketchy as this; the point is this is not sufficient hard evidence on which to base any conclusion for me, Kassirer said.

In particular, he noted that one thing the report examined were the employment effects of the genome projectan area in which he noticed a kind of circular logic going on in counting up the economic benefits.

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Did the human genome project really have a trillion dollar impact?

The $14.5 billion investment by the U.S. in the Human Genome Project, completed a decade ago, has paid off more than 60-fold in new jobs, drugs and a rapidly expanding genetics industry, an analysis has found.

The endeavor to map human DNA in its entirety created $966 billion in economic impact and $59 billion in federal tax revenue, according to the study released today by United for Medical Research and Battelle, two research advocacy groups.

Dozens of companies have started with the knowledge gained from the project, leading to new diagnostic tests and development of medicines that can be matched with gene variants linked to disease. The project triggered a new era in the life sciences, with new oncology drugs and screenings among the early developments in the field, said Greg Lucier, chief executive officer of Life Technologies Corp. (LIFE)

Up until that time, the pharmaceutical industry was able to have major impact on human health through blockbuster drugs that in retrospect were relatively simple, he said in a telephone interview. The ushering in of the genomic era was the beginning of truly reducing science to engineering, in terms of the understanding of life, he said.

Life Technologies also provided funding for the study. The Carlsbad, California-based maker of gene-sequencing machines agreed to be bought by Thermo Fisher Scientific Inc. (TMO) for $13.6 billion last April. Other companies that provide sequencing services or equipment include Illumina Inc. (ILMN) and Oxford Nanopore Technologies Ltd. The Human Genome Project also spurred consumer-focused genetics companies such as 23andMe Inc. that let people find out what diseases they might be at risk for or where their ancestry lies.

While it took almost $15 billion and more than a decade for the government-funded DNA effort to fully sequence a human genome for the first time, companies can now sequence a whole genome for about $1,000 and do it in a day.

The Human Genome Project was the starting point of that magnificent, incredible effort, Lucier said.

The market for gene tests may expand to $25 billion from $5 billion within a decade as more doctors use a patients genetic makeup to tailor treatments, according to a report last year from UnitedHealth Group Inc. (UNH), the largest U.S. health insurer.

This report illustrates the vital role that key federal research funding plays in growing the U.S. economy, creating new industries and innovative technologies and producing the diagnostics and treatments that can save lives, Carrie Wolinetz, president of United for Medical Research, said in a statement. She called the now-complete project the biggest undertaking in the history of the life sciences.

Some of biggest innovations have been in the field of oncology. The actress Angelina Jolie recently became the new face of breast cancer, after announcing that shed had a double-mastectomy upon discovering that she carried a gene that predicts about a 60 percent chance of developing the disease.

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Human Genome Project Spurred $966 Billion Sciences Boom