'More genes' needed to make life

By Paul Rincon
BBC News science reporter

The researchers used E. coli as the basis for their analysis

Scientists trying to make artificial life forms in the lab may have more work ahead of them than they thought.

The simplest life forms could require twice as many genes to survive than was previously believed, a research team claims in the journal Nature.

The "minimal genome" is the least number of genes an organism needs to survive in its environment.

The traditional way of identifying essential genes may label some as expendable when they are not.

The surprise was the metabolism got to be really rather larger than people had suggested the smallest metabolism could be Laurence Hurst, University of Bath

A US research team created the world's first synthetic virus in 2002, but scientists are divided about whether viruses are, strictly speaking, alive.

A team at Rockefeller University, US, has created small synthetic vesicles capable of expressing genes that resemble a crude kind of biological cell.

And Dr Craig Venter - the man behind the privately funded human genome sequence - has announced his intention to create a man-made microbe with the minimum number of genes needed to sustain life.

The work in Nature suggests they may have further to go than anyone had predicted.

Scientists identify minimal genomes by removing, or "knocking out", individual genes from a microbe's genome to see what effect this has on its ability to survive.

They can then infer which genes are essential to the organism, and which are not, arriving at a minimum number.

The authors of the Nature report say this "single gene knockout" method ignores the fact that bacterial cells have back-up mechanisms for synthesising the chemicals they need to survive.

Drop the genes

Researchers from the UK, Hungary and Germany, focused on two evolutionary offshoots of the bacterium Escherichia coli, or E. coli. These offshoots - Buchnera aphidicola and Wigglesworthia glossinidia - have evolved to live inside the aphid and the tstetse fly respectively.

US researchers have created vesicles that can express genes

Knowing the metabolic pathways used by E.coli and the lifestyles of Buchnera and Wigglesworthia, the researchers developed a mathematical test to predict which genes these microbes would need to survive in their environments.

"We predicted which genes Buchnera and Wigglesworthia might have by just knowing their ecology and what they have evolved from," co-author Professor Laurence Hurst, of the University of Bath, UK, told the BBC News website.

"Then we played with another model where we said: 'now we've got loads of nutrients, how small can the metabolism go?'"

"The surprise was the metabolism got to be really rather larger than people had suggested the smallest metabolism could be."

No alternative

The problem with the single gene knockout method, says Professor Hurst, is that it considers one chemical process at a time, ignoring what would happen if alternative ways of making the same chemical are knocked out simultaneously.

As soon as one "metabolic pathway" is removed, the alternative pathway becomes essential. Professor Hurst and colleagues suggest single gene knockout studies could underestimate minimal genomes by about 50%.

Dusko Ehrlich, of the Institut National de la Recherche Agronomique in France, who has published a minimum number of genes for the bacterium Bacillus subtilis, said the Nature paper dealt only with a sub-set of the total genes in Buchnera and Wigglesworthia.

"The paper deals only with biochemical reactions, not DNA synthesis, protein synthesis, or replication," he explained.

"They deal with precursors but don't deal with many macromolecules. Many essential genes are required for synthesis of macromolecules. But within what they look at, I don't have a quarrel with. It looks reasonable."

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