A minimal genome

Craig Venter unveils "synthetic life"          Craig Venter’s Brave New World    

 Mycoplasma laboratorium     Genome       Artificial life links

The field of molecular biology is currently engaged in the most extensive project of reverse engineering ever conceived: the elucidation of the molecular components and events that constitute living systems. One central question is simply stated: What is the minimal number of genes necessary to maintain the viability of a living system?

Apart from viruses, the smallest replicating biological systems known are the mycoplasmas (mollicutes). There are over 150 species of this class of cell-wall-free bacteria, some of which are human pathogens. Mycoplasmas apparently evolved from other bacteria by reduction of genome size: the smallest genome of the mycoplasmas is little more than twice the genome size of certain large viruses. Mycoplasmas are the smallest organisms that can be free-living in nature and self-replicating on laboratory media (viruses replicate only in bacteria and other cells). Mycoplasmas range from 125 to 250 nanometers in size. They change shape readily (pleomorphism) because they lack a cell wall, being bounded by a triple-layered lipoprotein membrane that contains a sterol.

The genome of Mycoplasma genitalium (an organism that causes one form of the urinary tract infection urethritis), which has been completely sequenced, consists of 580 kilobases comprising 517 genes (480 protein-coding genes; 37 genes for RNAs), and this is the smallest gene complement for any independently replicating cell so far identified.

... ... C.A. Hutchinson III et al (8 authors at 2 installations, US) now report the use of molecular genetic methods (global transposon mutagenesis) to identify nonessential genes in M. genitalium under laboratory growth conditions. The authors report their analysis suggests that 265 to 350 of the 480 protein-coding genes of M. genitalium are essential under laboratory growth conditions, including approximately 100 genes of unknown function. The authors conclude: "The presence of so many genes of unknown function among the essential genes of the simplest known cell suggests that all the basic molecular mechanisms underlying cellular life may not yet have been described. The essential gene set is not the same as the minimal genome. It is clear that genes that are individually dispensable may not be simultaneously dispensable. The data presented here suggest some specific experiments that could be carried out as a first step in the engineering of a cell with a minimal genome in the laboratory environment."

C.A. Hutchinson III et al: Global transposon mutagenesis and a minimal Mycoplasma genome. Science 10 Dec 99 286:2165. QY: J. Craig Venter, Celera Genomics, 45 West Gude Drive,
Rockville, MD 20850 US.


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Craig Venter’s Brave New World     

By RICHARD DAWKINS - RICHARDDAWKINS.NET
Updated: Monday, 24 May 2010 at 12:28 PM - An RDFRS Original

Craig Venter’s artificial bacterium debuted almost simultaneously with Svante Pääbo’s publication of the greater part of the Neanderthal genome. Put the two together and ask whether we could – or should – recreate a living, breathing Neanderthal. Of the technologies that would be required, the Venter team has proofed an important component. Dolly was cloned from an entire diploid genome of an adult sheep’s udder cell, dropped into an enucleated ovum. The Venter equivalent of Ian Wilmut’s achievement would be to go to the library (or in this case the Internet), take down the book labelled ‘Sheep Genome Project’ (or rather download the data files), and synthesize a complete set of sheep chromosomes from four bottles of chemicals labelled A, T, C and G. The synthetic genome would then be dropped into an enucleated sheep cell, as per Dolly.

While they were about it, the team might improve on the genome of any one donor sheep by substituting, say, wool-growing genes from The Champion Merino Genome Project and hardiness genes from The Soay Genome Project. Maybe some code from the Goat Genome Project to broaden the creature’s preferred diet, or from the Chamois Genome Project to give it a better head for heights? Perhaps even a Cut and Paste job from the Otter Genome Project, to give the über-sheep a taste for water sports.

We’d need to do something similar to re-grow a Neanderthal from Svante Pääbo’s data. Or, later, a computed intermediate between the chimpanzee and human genomes to re-create the 6-million-year-old common ancestor. And then, might a born-again Lucy split the difference again?

The technical difficulties would be formidable, but present progress suggests that they will be overcome. I leave the speciesist ethical difficulties on one side, except to note that ethical thinking, too, has a way of progressing as the decades go by. There is the harder problem that Pääbo’s Neanderthal sequence is only 60 percent complete, and 100 percent may be unattainable. Presumably the residue would be coloured in from the H. sapiens genome, and that could create technical problems as well as compromise the authenticity of the clone as a ‘true’ Neanderthal.

But Neanderthal bones are tens of thousands of years old. Should we disinter Charles Darwin’s bones from Westminster Abbey with the same insouciance as the Roman Catholic Church is now displaying toward the remains of his contemporary, Cardinal Newman? Might a new identical twin brother of the great naturalist ride shotgun to Craig Venter’s future twin, on a round-the-world DNA-harvesting voyage? Could Darwin Junior be mathematically enhanced by a few judicious splicings from the Albert Einstein Genome Project? Or get a head-start in molecular genetics by strategic borrowing from the Francis Crick Genome Project? The Jeremy Bentham Genome Project might suffer utilitarian doubts over whether the taxidermic curiosity in the Entrance Hall of University College, London still contains any of his authentic remains.

Of course no steps were taken to preserve the DNA of any of these great men. Today’s equivalents don’t need to be cryogenically preserved for the Craig Venters of the future. Nothing so messy or expensive. Give or take some epigenetic mark-ups, a simple computer disk is all it takes: just miles and miles of A, T, C, G.

And the J Craig Venter Genome Project is already on line...