Category Archives: Genome

Genome Holiday Card

By: AccurateDesign

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Genome Holiday Card - Video

Common Pathway of Carcinogenesis
Common Pathway of Carcinogenesis Carcinogenic agents are heterogeneous, physical chemical and biological. Yet they all share a common mechanism. For the unified theory of carcinogenesis I...

By: Gershom Zajicek M.D,

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Common Pathway of Carcinogenesis - Video

PUBLIC RELEASE DATE:

29-Sep-2014

Contact: David Gilbert degilbert@lbl.gov DOE/Joint Genome Institute @doe_jgi

The U.S. Department of Energy Joint Genome Institute (DOE JGI), a DOE Office of Science user facility, has announced that 32 new projects have been selected for the 2015 Community Science Program (CSP). From sampling Antarctic lakes to Caribbean waters, and from plant root micro-ecosystems, to the subsurface underneath the water table in forested watersheds, the CSP 2015 projects portfolio highlights diverse environments where DOE mission-relevant science can be extracted.

"These projects catalyze JGI's strategic shift in emphasis from solving an organism's genome sequence to enabling an understanding of what this information enables organisms to do," said Jim Bristow, DOE JGI Science Deputy who oversees the CSP. "To accomplish this, the projects selected combine DNA sequencing with large-scale experimental and computational capabilities, and in some cases include JGI's new capability to write DNA in addition to reading it. These projects will expand research communities, and help to meet the DOE JGI imperative to translate sequence to function and ultimately into solutions for major energy and environmental problems."

The CSP 2015 projects were selected by an external review panel from 76 full proposals received that resulted from 85 letters of intent submitted. The total allocation for the CSP 2015 portfolio is expected to exceed 60 trillion bases (terabases or Tb)or the equivalent of 20,000 human genomes of plant, fungal and microbial genome sequences. The full list of projects may be found at http://jgi.doe.gov/our-projects/csp-plans/fy-2015-csp-plans/. The DOE JGI Community Science Program also accepts proposals for smaller-scale microbial, resequencing and DNA synthesis projects and reviews them twice a year. The CSP advances projects that harness DOE JGI's capability in massive-scale DNA sequencing, analysis and synthesis in support of the DOE missions in alternative energy, global carbon cycling, and biogeochemistry.

Among the CSP 2015 projects selected is one from Regina Lamendella of Juniata College, who will investigate how microbial communities in Marcellus shale, the country's largest shale gas field, respond to hydraulic fracturing and natural gas extraction. For example, as fracking uses chemicals, researchers are interested in how the microbial communities can break down environmental contaminants, and how they respond to the release of methane during oil extraction operations.

Some 1,500 miles south from those gas extraction sites, Monica Medina-Munoz of Penn State University will study the effect of thermal stress on the Caribbean coral Orbicella faveolata and the metabolic contribution of its coral host Symbiodinium. The calcium carbonate in coral reefs acts as carbon sinks, but reef health depends on microbial communities. If the photosynthetic symbionts are removed from the coral host, for example, the corals can die and calcification rates decrease. Understanding how to maintain stability in the coral-microbiome community can provide information on the coral's contribution to the global ocean carbon cycle.

Longtime DOE JGI collaborator Jill Banfield of the University of California (UC), Berkeley is profiling the diversity of microbial communities found in the subsurface from the Rifle aquifer adjacent to the Colorado River. The subsurface is a massive, yet poorly understood, repository of organic carbon as well as greenhouse gases. Another research question, based on having the microbial populations close to both the water table and the river, is how they impact carbon, nitrogen and sulfur cycles. Her project is part of the first coordinated attempt to quantify the metabolic potential of an entire subsurface ecosystem under the aegis of the Lawrence Berkeley National Laboratory's Subsurface Biogeochemistry Scientific Focus Area.

Banfield also successfully competed for a second CSP project to characterize the tree-root microbial interactions that occur below the soil mantle in the unsaturated zone or vadose zone, which extends into unweathered bedrock. The project's goal is to understand how microbial communities this deep underground influence tree-based carbon fixation in forested watersheds by the Eel River in northwestern California.

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2015 DOE JGI's science portfolio delves deeper into the Earth's data mine

September 29, 2014

Brett Smith for redOrbit.com Your Universe Online

New research from the University of California, Santa Cruz has revealed that two sets of primate genes have been battling it out over the millennia and this conflict has driven the complexity of primate genomes.

Published on Sunday in the journal Nature, the study found that genome jumping retrotransposons are constantly developing new ways to escape repression by another set of genes called repressors.

We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about, said study author Sofie Salama, a research associate at the UC Santa Cruz Genomics Institute who led the study.

Retrotransposons are segments of genetic code that can copy themselves and then insert that copy back into the genome. These events can interrupt genes and trigger disease, based on where a new copy slips into the genome. Frequently the effect is negligible, and occasionally the effect is advantageous, potentially enhancing gene expression.

The high chance of negative outcomes means natural selection favors mechanisms that prevent jumping events in the form of repressor genes and proteins.

The repressors named in the new study are part of the biggest category of gene-regulating proteins in mammals, called KRAB zinc finger proteins. The human genome has more than 400 genes for these repressive DNA-binding proteins, and about 170 of them have developed since primates split from other mammals.

The way this type of repressor works, part of it binds to a specific DNA sequence and part of it binds other proteins to recruit a whole complex of proteins that creates a repressive landscape in the genome, Salama said. This affects other nearby genes, so now you have a potential new layer of regulation available for further evolution.

Previous research on KRAB zinc finger proteins found they repress jumping genes in mouse embryonic stem cells. In the new study, scientists placed primate retrotransposons in mouse embryonic stem cells that had a single human chromosome. The primate jumping genes suddenly sprang to life in the mouse cells. The study team developed a test to see which individual KRAB proteins could turn off a primate jumping gene in the mouse cell system.

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Evolutionary Arms Race Within The Human Genome

15 hours ago Professor Vanessa Hayes in the field. Credit: Chris Bennett photography

What can DNA from the skeleton of a man who lived 2,330 years ago in the southernmost tip of Africa tell us about ourselves as humans? A great deal when his DNA profile is one of the 'earliest diverged' oldest in genetic terms found to-date in a region where modern humans are believed to have originated roughly 200,000 years ago.

The man's maternal DNA, or 'mitochondrial DNA', was sequenced to provide clues to early modern human prehistory and evolution. Mitochondrial DNA provided the first evidence that we all come from Africa, and helps us map a figurative genetic tree, all branches deriving from a common 'Mitochondrial Eve'.

When archaeologist Professor Andrew Smith from the University of Cape Town discovered the skeleton at St. Helena Bay in 2010, very close to the site where 117,000 year old human footprints had been found dubbed "Eve's footprints" he contacted Professor Vanessa Hayes, a world-renowned expert in African genomes.

At the time, Hayes was Professor of Genomic Medicine at the J. Craig Venter Institute in San Diego, California. She now heads the Laboratory for Human Comparative and Prostate Cancer Genomics at Sydney's Garvan Institute of Medical Research.

The complete 1.5 metre tall skeleton was examined by Professor Alan Morris, from the University of Cape Town. A biological anthropologist, Morris showed that the man was a 'marine forager'. A bony growth in his ear canal, known as 'surfer's ear', suggested that he spent some time diving for food in the cold coastal waters, while shells carbon-dated to the same period, and found near his grave, confirmed his seafood diet. Osteoarthritis and tooth wear placed him in his fifties.

Due to the acidity of the soil within the region, acquiring DNA from skeletons has proven problematic. The Hayes team therefore worked with the world's leading laboratory in ancient DNA research, namely that of paleogeneticist Professor Svante Pbo at the Max Planck Institute for Evolutionary Anthropolgy in Leipzig, Germany, who successfully sequenced a Neanderthal.

The team generated a complete mitochondrial genome, using DNA extracted from a tooth and a rib. The findings provided genomic evidence that this man, from a lineage now presumed extinct, as well as other indigenous coastal dwellers like him, were the most closely related to 'Mitochondrial Eve'.

The study underlines the significance of southern African archaeological remains in defining human origins, and is published in the journal Genome Biology and Evolution, now online.

"We were thrilled that archaeologist Andrew Smith understood the importance of not touching the skeleton when he found it, and so did not contaminate its DNA with modern human DNA," said Professor Hayes.

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Ancient human genome from southern Africa throws light on our origins

17 hours ago Brachypodium distachyon is being studied by bioenergy researchers as a model system for grasses that could serve as sustainable plant biomass sources for biofuels. Credit: Sarah Gregg via Flickr, CC BY-NC-SA 2.0

Researchers used deep sequencing to look at whole-genome sequence variation in seven lines of the model grass Brachypodium distachyon and found previously unannotated genes. They also looked at genome-wide gene expression under drought-stress conditions.

Hundreds of genes not present in the reference genome and many unannotated genes were identified through this process, leading to the development of a public database for visualizing and investigating sequence variants in these lines.

Changes in the global climate, and closer to home, the ongoing drought in California, emphasize the importance of developing crops for fuel and food security that can tolerate low-water conditions. The grass Brachypodium distachyon, Brachy for short, is a model for candidate biomass feedstock crops, particularly those that can be grown on marginal lands. To assist in studying candidate biomass crops, a reference Brachy genome was sequenced and published by the U.S. Department of Energy Joint Genome Institute (DOE JGI), a DOE Office of Science user facility, in collaboration with U.S. Department of Agriculture researchers through the Community Science Program.

A single plant reference genome, however, cannot reflect all of the potential gene variants in a species, and Brachy is found in many climate zones, which would suggest that there are several adaptations for each habitat. In a study reported in the August issue of The Plant Journal, a team including DOE JGI researchers conducted deep sequencing ("the equivalent of 900-fold sequence depth of the 272 Megabase B. distachyon genome," according to the researchers) on several Brachy lines.

To understand the roles of the genome-wide sequence variants they found, the team conducted a series of experiments in which they simulated drought-stress conditions on several Brachy plants. They then looked at the transcripts from the plants to identify genes involved in the plant's response to drought stress. The team found nearly 900 genes "that responded significantly" to water stress.

"Our validated datasets demonstrate the existence of extensive natural variation in B. distachyon," the team concluded, "[and] demonstrates the utility of our resequencing data as a foundation for studies of natural diversity in B. distachyon."

Explore further: A decade of improvements on the reference green alga genome

More information: Gordon SP et al. "Genome diversity in Brachypodium distachyon: deep sequencing of highly diverse inbred lines." Plant J. 2014 Aug;79(3):361-74. DOI: 10.1111/tpj.12569.

The high-quality genome sequence of the tiny single-celled alga Chlamydomonas reinhardtii has proved useful for researchers studying photosynthesis and cell motility.

Excerpt from:
Unannotated genes identified through sequencing multiple lines of brachypodium distachyon

Researchers at the Department of Energy's Oak Ridge National Laboratory are the first team to sequence the entire genome of the Clostridium autoethanogenum bacterium, which is used to sustainably produce fuel and chemicals from a range of raw materials, including gases derived from biomass and industrial wastes.

The ORNL work was funded by LanzaTech, a biotechnology company based in Illinois with an innovative carbon recycling process. LanzaTech's gas fermentation platform uses proprietary microbes for efficiently converting carbon-rich waste gases and residues into useful fuels and chemicals.

Successfully sequencing Clostridium autoethanogenum -- classified as a complex, class III microbe because of its many repeating units of DNA bases -- has been of significant interest to the biotechnology industry. A Biotechnology for Biofuels paper co-authored by ORNL's Steve Brown and Miriam Land, University of Tennessee doctoral student Sagar Utturkar and collaborating LanzaTech researchers generated a top-5-percent rating from Altmetric, an online rating system that measures the volume and value of recognition an article receives from research communities and media outlets.

"With the complete genomic sequence, we will have a better understanding of the microbe's metabolism and mutations that will enable LanzaTech to make modifications to the wild-type, or naturally occurring, strain for optimizing the conversion of waste into fuel," Brown said. "Our ORNL lab has a lot of experience sequencing genomes, and we have the analytic capability to tackle this project."

The research team sequenced the more than 4.3 million base pairs of DNA that make up the organism's genome using RS-II long-read sequencing technology developed by Pacific Biosciences (PacBio).

Although long-read sequencing technologies still struggle with high error rates, they promise to advance the biotechnology industry by making it possible to sequence microorganisms with many repeating sequences, such as Clostridium autoethanogenum, within a reasonable amount of time at reasonable cost. The ORNL team performed a greater number of reads and used data algorithms to correct for errors associated with the long-read technology. The team also compared the RS-II long-read results to two short-read technologies, concluding the short-read technologies were unable to sequence the entire genome because of the bacterium's repetitive sequences, as expected.

"In our paper we compared three generations of sequencing technologies and explained why the long-read technology was able to finish the genome," Brown said. "Now, ORNL is independently looking at six different organisms using PacBio to compare and contrast experiences using this technology."

The project also revealed information about the genetic history of Clostridium autoethanogenum through short DNA sequences known as CRISPR systems, which retain genetic mutations such as those created during a viral infection that are subsequently passed on to future generations of a microbe. CRISPR systems are important indicators of strengths and vulnerabilities that biotechnology companies like LanzaTech look for when genetically modifying a microbe.

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The above story is based on materials provided by Oak Ridge National Laboratory. Note: Materials may be edited for content and length.

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Bacterial genome important to fuel and chemical production sequenced

The human body is pretty great, but it could use a few tweaks from time to time.

Thats the philosophy of a group of scientists developing a way to edit genomes, a cutting-edge field that could be the answer to many significant diseases and help researchers better understand the human body.

Thanks to these discoveries, scientists can now replace specific parts of the DNA of cells, making a disease weaker or a person less susceptible to the disease, for example. In the case of HIV, which is unable to infect people without a specific protein, genome editing can modify the specific part of the genome so the person no longer produces the protein and the person can no longer be infected with HIV.

We take out cells, correct it ... and put the cell back into the person, said Feng Zhang, a researcher at the Broad Institute in Cambridge. Its a biotechnology that allows us to go into the genome, the DNA of a cell, and make very exact changes within the DNA.

It is process that can take weeks, requiring the removal of in the case of HIV all of the blood cells so the change can be made to the cells.

Zhang said sickle cell anemia is another disease that could be tackled by genome editing, but any virus including Ebola that has a mutation that can be exploited at the genetic level could be addressed by the process.

He is credited with developing CRISPR, a new method of genome editing that his colleagues say made the practice dramatically more widespread.

Any lab with any biological expertise can do it, said Charles Gersbach of Duke University, who is studying genome editing for genetic diseases.

By breaking the DNA in a specific place, the cells self-repair mechanism is triggered, but instead of reforming the same DNA sequence, CRISPR provides a new template.

When you make a cut in the region you want to fix, you can fool the cell into putting in the right information, Zhang said.

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Fighting diseases via genome editing

15 hours ago

New findings by scientists at the University of California, Santa Cruz, suggest that an evolutionary arms race between rival elements within the genomes of primates drove the evolution of complex regulatory networks that orchestrate the activity of genes in every cell of our bodies.

The arms race is between mobile DNA sequences known as "retrotransposons" (a.k.a. "jumping genes") and the genes that have evolved to control them. The UC Santa Cruz researchers have, for the first time, identified genes in humans that make repressor proteins to shut down specific jumping genes. The researchers also traced the rapid evolution of the repressor genes in the primate lineage.

Their findings, published September 28 in Nature, show that over evolutionary time, primate genomes have undergone repeated episodes in which mutations in jumping genes allowed them to escape repression, which drove the evolution of new repressor genes, and so on. Furthermore, their findings suggest that repressor genes that originally evolved to shut down jumping genes have since come to play other regulatory roles in the genome.

"We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about," said Sofie Salama, a research associate at the UC Santa Cruz Genomics Institute who led the study.

Retrotransposons are thought to be remnants of ancient viruses that infected early animals and inserted their genes into the genome long before humans evolved. Now they can only replicate themselves within the genome. Depending on where a new copy gets inserted into the genome, a jumping event can disrupt normal genes and cause disease. Often the effect is neutral, simply adding to the overall size of the genome. Very rarely the effect might be advantageous, because the added DNA can itself be a source of new regulatory elements that enhance gene expression. But the high probability of deleterious effects means natural selection favors the evolution of mechanisms to prevent jumping events.

Scientists estimate that jumping genes or "transposable elements" account for at least 50 percent of the human genome, and retrotransposons are by far the most common type.

"There have been successive waves of retrotransposon activity in primate evolution, when a transposable element changed to become expressed and replicated itself throughout the genome until something turned it off," Salama said. "We've discovered a major mechanism by which the genome is able to shut down these mobile DNA elements."

The repressors identified in the new study belong to a large family of proteins known as "KRAB zinc finger proteins." These are DNA-binding proteins that repress gene activity, and they constitute the largest family of gene-regulating proteins in mammals. The human genome has over 400 genes for KRAB zinc finger proteins, and about 170 of them have emerged since primates diverged from other mammals.

According to Salama, her team's findings support the idea that expansion of this family of repressor genes occurred in response to waves of retrotransposon activity. Because repression of a jumping gene also affects genes located near it on the chromosome, the researchers suspect that these repressors have been co-opted for other gene-regulatory functions, and that those other functions have persisted and evolved long after the jumping genes the repressors originally turned off have degraded due to the accumulation of random mutations.

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Human genome was shaped by an evolutionary arms race with itself

Scientists said they believe they are on the cusp of developing new strains of livestock using DNA technology that may improve meat and milk production while alleviating consumer fears, according to an MIT Technology Review article published in September.

A June poll by ABC News found that barely more than a third of the public believes that genetically modified foods are safe to eat, yet a consensus among scientists and industry professionals alike said the exact opposite.

While there is controversy surrounding genetically modified organisms, most concerns center around genetically modified plants, developed by splicing specific DNA from one plant species into another. Scientists are developing a new technology called genome editing they believe will revitalize the concept of genetically modified livestock since the process involves genes in animals that are currently in the food supply.

Jennifer Bormann, associate professor of animal breeding and genetics, said using this technology can improve cattle quality without changing the quality of meat or milk consumers get from the animal.

When changing one specific gene, all other genes are unaffected, Bormann said. It would be possible to change a gene that affects meat or milk. If, for example, you wanted to make the meat more tender, you might change a gene that has been proven to make meat tender.

She also said the genome editing technology doesnt create any food safety concerns because, we have been doing it for a long time in plants, and the same product could be created without the use of this technology.

We could do the same thing with traditional breeding by crossing and backcrossing repeatedly to introgress the gene of interest, Bormann said. It would just take many generations of crossing and many years.

Karen Batra, director of food and agriculture communications for the Biotechnology Industry Organization, said genetic engineering is the deliberate modification of the animals genome using techniques of modern biotechnology.

Many might be surprised to know that genetically engineered animals are just like normal cows, pigs, goats and fish only better, Batra said. They all contain a specific gene that makes them better than their conventional counterparts.

Batra also said that by incorporating genes from other organisms in a process called transgenesis, genetically engineered animals are being developed to address five broad goals. The goals are to advance human health, enhance food production and quality, mitigate environmental impact, optimize animal welfare and improve industrial products.

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Genome editing opens possibilities for genetically modified livestock