Scientists have shown that E. coli – one of the best known and extensively studied organisms in the world – remains an enigma that may hold the key to human diseases, such as cancer.
The team, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and based at the University of Dundee has examined the genome sequence of this workhorse of the laboratory and spotted three previously unknown genes that, it turns out, are essential for the survival of E. coli and one out of the three could also be implicated in cancer or developmental abnormalities in humans. These mystery genes are also found in numerous other creatures, suggesting a vital role for them across many species. The research will be published in the 1 August edition of the Journal of Bacteriology.
Scientist Live spoke with Prof. Tracy Palmer, one of the principal researchers, about the study.
Considering how ubiquitous and well studied E. coli is, how have three key genes managed to go undetected for this long?
It is most likely because these genes are essential for survival of the organism. A common way that biologists discover genes is to find mutants where the function of the gene is affected. In this case it was not possible because mutants in any of these three genes quickly die.
How did you discover the genes?
Actually the genes were discovered when the genome of E. coli was sequenced and published. One of the big surprises that came out of the E. coli genome sequence was the existence of many genes that had never been detected before. Some of these many novel genes are unique to E. coli, but some are found in many other species. The three genes that we have studied are found in all bacteria, suggesting that they play a universal function in all bacteria.
Where on E. coli's genome are each of the three genes located?
The three genes are scattered across the genome of E. coli at three entirely different locations. But what is very interesting is that in some other bacteria, such as the soil bacterium Bacillus subtilis and the hospital superbug MRSA, the three genes lie next to each other. This actually gave us our first clue that the three genes might be related to each other.
What roles do you believe each of the three genes play? One of them, ygjD is present in the human genome. What is the potential significance of this? Can you speculate on how the commonality occurred?
We don't know as yet what these genes do, so any role would be speculation at the moment. One of the three genes, called ygjD in E. coli, is found in all genomes, including humans. It is therefore likely that it was present in the genome of the earliest form of life, which gave rise to all the organisms on earth. This means that the protein coded by the gene has a basic and essential function in the survival of the cell. We can only guess at this essential function but one idea is that it is a protease, which is a protein that destroys other proteins (for example when they become old or damaged. Damaged proteins are extremely dangerous to cells and are implicated in diseases such as alzheimers and diabetes-linked blindness). The other two genes are found only in bacteria, but they are linked in with the function of YgjD. Our work has shown that these two genes help to regulate the function of YgjD, making sure that it carries out its specific job in the right place at the right time. We think humans have found a different way to regulate the function of YgjD which is why these other two genes are missing.
What is the next step for your research?
The next step is to find out what these genes actually do. We know that they code for proteins, and that the proteins must have an essential role in the bacterial lifecycle. One approach we are going to take is to examine YgjD to see if we can show it is a protease, and, if so, what kind of proteins it will destroy. Our guess is that it specifically recognises damaged proteins, so we want to find out what kind of damage we need to do to proteins so that they will be destroyed by YgjD. We can then look in human cells to see if the human protein behaves in the same way.
(Reporting by Marc Landas)
