Saturday, 19 December 2015

7th genome of Christmas: Bread, Beer and Wine.

When you first think of domesticated organisms, dogs might come to mind (our earliest domestication), or perhaps wheat, or cattle or rice. But you might easily overlook single-celled yeast: the key active agreement in both bread and alcohol, and a great enabler of the agricultural revolution in Europe. 

Wild yeast lives on fruit and seeds, and is dispersed by the wind. The earliest use of these wild organisms involved capturing them to make alcohol (wine) and to make sourdough bread rise. For the routine production of beer and bread, brewers and bakers kept cultures of 'good' yeast, eventually selecting for specific strains of Saccharomyces cerevisiae: a single-celled fungus that can live both in aerobic (oxygen present) and anaerobic (no oxygen) conditions.

As genetics and molecular biology took shape, researchers fell in love with this miniature fungus. It is a eukaryote, with a nucleus, signalling pathways, cell division and other conserved features. From the laboratory husbandry point of view, it is closer to bacteria: you grow it on media plates, its commonest life cycle stage is haploid (one copy of the genome) rather than the more commonplace diploid. Despite its mainstay 'growth' haploid mode, yeast also has a sex life (becoming diploid), which you can manipulate and use for genetics. 

After E. coli, it probably has the most manipulable DNA, letting you swap in or out any piece of DNA (you can even insert entire chunks of DNA from other species if you want to, making “YAC”, Yeast Artificial Chromosomes).

So many basic molecular discoveries have their origins in yeast that it is impossible to list them all. Everything from understanding the cell cycle (though a separate African brewer’s yeast, S. pombe, took a star turn as well), through mapping intracellular signalling pathways, to laying down the fundamental aspects of transcription (making RNA from DNA) and translation (making proteins from RNA). Each discovery shows in some way that the vast majority of the cellular machinery one can study in yeast is pretty much at work - sometimes gene-for-gene - in each and every one of our own cells. 

So it's not surprising that yeast was an early target for genome sequencing. This life form was sequenced by a consortium of individual labs all over the world, using the early, more manual technologies. There was some automation and factory-like sequencing, but a lot of the work was done Old School: individual postdocs and technicians pouring gels and reading off each piece of DNA in a bespoke fashion. This was much in the tradition of crafting brewers-yeast-based beers, and as such can be considered an artisanal genome sequence. In 1996 it was published: the first eukaryotic genome.

Yeast is one of the most engineered of all species. One can order up any gene knockout, or a collection of all yeast genes knocked out, with barcodes. One can have any protein tagged, and use that tag for cellular imaging or mass spectroscopy. Huge systematic crosses, direct evolution or growing in controlled environments are feasible on a robotic scale with yeast - and the genome sequence provides a pivotal part of the infrastructure for this kind of work.

So raise a glass to yeast! Its genome sequence, coupled with its amazing genome engineering and ease of growth, has placed it firmly in the premier spot as an organism for both basic cellular biology and biotechnology.