Massive reanalysis of genome data solves case of the lethal genes

Oct 18, 2007

It is better to be looked over than overlooked, Mae West supposedly said. These are words of wisdom for genome data-miners of today. Data that goes unnoticed, despite its widespread availability, can reveal extraordinary insights to the discerning eye. Such is the case of a systematic analysis by the U.S. Department of Energy Joint Genome Institute (DOE JGI) of the massive backlog of microbial genome sequences from the public databases.

The survey identified genes that kill the bacteria employed in the sequencing process and throw a microbial wrench in the works. It also offers a possible strategy for the discovery of new antibiotics. These findings are published in the Oct. 19 edition of the journal Science.

In nature, promiscuous microbes share genetic information so readily that using genes to infer their species position on the evolutionary tree of life was thought to be futile. Now, researchers at DOE JGI have characterized barriers to this gene transfer by identifying genes that kill the recipient bacterium upon transfer, regardless of the type of bacterial donor. These lethal genes also provide better reference points for building phylogenic trees—the means to verify evolutionary relationships between organisms.

“At DOE JGI, we are responsible for producing and making publicly available genomes from hundreds of different microbes, most of which are relevant to advancing the frontiers of bioenergy, carbon cycling, and bioremediation,” said Eddy Rubin, DOE JGI Director. “We realized that sequencing a genome is like conducting a massive experiment in gene transfer. By checking which genes could not be sequenced, we discovered barriers to transfer.”

The industrial-scale “shotgun” DNA sequencing strategy typically involves sheering the organism’s DNA into manageable fragments, and then inserting these fragments into a disarmed strain of E. coli, which is used as an enrichment culture—to grow up vast amounts of the target DNA. The team led by Rubin showed that this sequencing process mimics the transmission of DNA from one organism to another, a mechanism called horizontal gene transfer. This phenomenon occurs in nature, allowing one organism to acquire and use genes from other organisms. While this is an extremely rare event in animals, it does occur frequently in microorganisms and is one of the main sources for the rapid spread of antibiotic resistance among bacteria.

“When you sequence a genome, you never get the whole genome reconstructed in one pass,” said Rubin. “You always get gaps in the assembly. This is annoying, expensive, and compels us to close the gaps and finish the puzzle so that we could tell the story behind the sequence. Our breakthrough was in understanding that gaps occur because some genes cannot be transferred to E. coli—because they are lethal.”

So Rubin and his colleagues sifted through more than nine billion nucleotides to assess gaps in 80 different genomes. They found that the same genes, over and over again, caused these gaps, meaning that they could not be transferred into the E. coli.

“We use the bits that people usually throw away, the gaps of information keeping us from finishing an assembly,” Rubin said. “We identified a set of genes that, if you add another copy or you tweak its expression, the host dies.

“The genes we categorized, while providing us a lesson in the evolutionary history of the organism, now suggest a short-cut for finishing genomes,” Rubin said. “In addition, it offers a new strategy for screening molecules that may represent the next generation of broad-spectrum antibiotics. We expect that many organisms, not just E. coli, are susceptible to being killed if they take up certain genes that are over-expressed. We have strong evidence that most microbes behave like that.”

Source: DOE/Joint Genome Institute

Explore further: Researchers create DNA repair map of the entire human genome

Related Stories

Understanding genetic diversity of bacteriophages

Apr 29, 2015

Over the last seven years, thousands of undergraduate students have joined the effort to sequence and analyze the genomes of bacteria-infecting viruses as part of the Howard Hughes Medical Institute's Science ...

Longer DNA fragments reveal rare species diversity

Apr 01, 2015

A challenge in metagenomics is that the more commonly used sequencing machines generate data in short lengths, while short-read assemblers may not be able to distinguish among multiple occurrences of the ...

The origins of polarized nervous systems

Mar 03, 2015

(Phys.org)—There is no mistaking the first action potential you ever fired. It was the one that blocked all the other sperm from stealing your egg. After that, your spikes only got more interesting. Waves ...

Recommended for you

Most people eager to know the secrets of their genetics

Apr 29, 2015

A survey of nearly 7000 people has revealed that 98 per cent want to be informed if researchers using their genetic data stumble upon indicators of a serious preventable or treatable disease. The study, which ...

The map of the body's proteins

Apr 28, 2015

Finished after 12 years' work: A pictorial atlas of the body's building blocks; proteins. A total of 13 million images have been collected into a searchable database in a collaboration which has involved ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Keter
1 / 5 (1) Oct 19, 2007
What has the Dept. of ENERGY got to do with GENOME research? That is a partnership that make no sense and sounds rather soylent greenish. Huh?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.