Thursday, March 31, 2016

A new leader in minimalistic genomes is born

Thanks to the work of scientists at the J. Craig Venter Institute in San Diego, CA, a new minimalistic microbe has been brought into the world. Through genome engineering, they have created a synthetic bacterium called Syn 3.0 that requires only 531,000 bases in its genome to grow with a doubling time of 3 hours in the laboratory. The next smallest free-living organism, Mycoplasma genitalium, has a genome of 600,000 bases, but grows with a doubling time of about 2 weeks. For comparison, consider the more well-known bacterium, Escherichia coli, which has a genome of 4,639,221 bases and a replication time of about 30 minutes in the laboratory. But what makes this new organism, which is approximately one-ninth the size of E. coli’s genome, able to survive and grow so readily? This question is especially puzzling in light of the fact that approximately one-third of Syn 3.0's genome codes for genes of unknown function.

Ever since the invention of genome sequencing, scientists have been identifying genes of unknown function. Even in the most well-studied of organisms, like the mouse, almost 96% of the genome remains of unknown function. Many of these segments are considered important for higher organization of the genome, allowing tight regulation of expression of the genes that code for specific RNAs and proteins. Bacteria tend to have the most completely annotated genomes of the model organisms due to their simplicity. In E. coli, 66% of the genes are of known function, and as much as 76% of the genome can be assigned a function by biochemical analysis software. Since approximately 3 million of E. coli’s 4 million bases of genetic material have known functions, it is rather shocking to find another bacterium that contains so many segments with unknown functions. Since Syn 3.0 has the smallest genome the researchers at the Venter Institute could engineer that could successfully sustain life, this suggests that we still do not know the functions of many essential genes.

In order to identify the function of genes of unknown function, many approaches can and have traditionally been used by researchers. The oldest method is to use random mutagenesis. Through this technique, you are able to use chemical mutagens or electromagnetic radiation to induce changes in different bases throughout the genome. After mutagenesis, you can identify what processes the organism can no longer perform. Sequencing can allow you to identify where the mutations you introduced occurred, thus helping link those genes with a molecular process. If you are only interested in one molecular process, you can design a screen to specifically pick out mutants that are deficient in this process for analysis.

More recent advances in genetic engineering have allowed for more sophisticated analyses. You can now delete a specific gene of interest and observe the phenotype. Alternatively, you can tag a gene with a marker, so that the specific protein produced is linked to a fluorophore or tag. This allows you to identify where and when the protein is expressed. The advent of new genetic engineering technologies, which made production of Syn 3.0 possible, will also enable us to discover the functions of those unknown genes.

The invention of this novel minimalistic microbe shines new light on our true lack of understanding of genetic material in organisms. By improving our knowledge of this unique bacterium, we can hope to improve our understanding of our own genome, and that of our many pathogens. Discoveries made from Syn 3.0 may be the key to great steps forward in understanding the genetic basis of disease and finding cures for the future.