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. colibecause 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.
|Contact: David Gilbert|
DOE/Joint Genome Institute