An international team has been working out how few genes a bacterium needs to survive, writes Dick Ahlstrom
There are genes you might like to have and genes you can't do without. The bacterium Bacillus subtilis needs 271 of them to stay alive, according to Irish scientists involved in a remarkable study of the number of genes necessary to sustain bacterial life. The joint European-Japanese research was published this month in the US-based Proceedings Of The National Academy Of Sciences.
"We were involved in a similar project to sequence the Bacillus subtilis genome," says Prof Kevin Devine, head of the genetics department at Trinity College in Dublin. The genome reached the public via the journal Nature in 1997. "This is really a follow-on from publishing the genome. People wanted to know how many of the genes were essential."
B subtilis has 4,100 genes, too many for one laboratory to tackle. So 19 European and 11 Japanese labs were involved in the study. "We inactivated each gene, and we looked at a whole variety of characteristics about that gene," says Devine. Each team started with a nutrient-packed broth in which to grow their bacteria. "You grow the bug under really rich conditions, \ everything it could possibly need, then you begin to knock out genes."
Laboratories contributed "knockout" B subtilis forms with specific genes inactivated. These changed forms were then forwarded to participating labs, which put the bacteria through a battery of 50 tests in a "functional analysis" that helped explain what effect the loss of a gene had on the organism. The Trinity group looked at the response of each knockout B subtilis to oxidative stress, the damage caused by the presence of free reactive oxygen. Other teams looked at bacterial growth, change in nutrient supply, heat shock, exposure to metals and many other conditions to understand the function of each gene.
By a process of elimination, the researchers found the core group of 271 genes the bacterium needs to survive. The great majority were associated with just a handful of cell-metabolism processes. Three key functions included genes linked to DNA replication, the business of producing copies of the cell's genetic blueprint; genes involved in RNA metabolism, RNA being the "recipe" derived from DNA that cells use to produce essential proteins; and protein synthesis, the manufacture of the proteins needed for cell activity.
Now researchers can check the genomes of other species to see if these same genes exist or were dropped. There is a high degree of genetic conservation with these core genes, says Devine. "Eighty per cent of these genes are present in all bacteria with a genome greater than three megabases," - 3 million steps in its genetic code - he says. "That is a high percentage, and they are key essential genes. They are highly conserved across bacteria."
The researchers also looked at organisms with some of the smallest of genomes, including the bacterium Mycoplasma genitalium. This parasitic organism, which thrives in the urinary tract, has just 480 genes, shedding all others in an evolutionary drive towards the ultimate in simplicity and a condensed genome. Yet even this stripped-down bug, which has no cell walls and just 0.58 megabases, compared with B subtilis's 4.2, still retains 57 per cent of the core 271 essential genes.
"They don't get lost as the genome gets smaller. One of the things it tells us is that, in biological systems, a particular solution will be found to solve a problem," says Devine. "Once found, nature sticks with it. It is highly conserved across all life."
The international team was able to pinpoint the purpose of almost all of the core genes. "Of the 271, only 11 couldn't be assigned a function."
The study will add to a better understanding of the B subtilis genome and to our knowledge of our own genome. We too will share a certain number of these conserved genes. Of equal interest will be the genetic alternatives devised to replace genes bypassed in the evolutionary process.