Next Tuesday’s #microtwjc paper will be “Total synthesis of a functional designer eukaryotic chromosome“, published last week or so in Science (you may have also seen the accompanying media attention). Apologies for it not being open access but the importance of this paper overshadowed that need. I think. If anyone has any problems accessing it just let me know via this or on twitter.
This paper documents the design, building and biological characterisation of a synthetic yeast chromosome, specifically chromosome III. For a primer on yeast genetics have a look at this. This is the first chromosome to be generated in what has been called the ‘yeast 2.0′ project - an international effort to generate a yeast with a completely synthetic genome (and actually carried out mainly by undergraduates). The paper is important for a number of reasons: 1) yeast is a model organism in its own right, engineering of a complete chromosome (or genome) will aid our understanding of not just yeast biology but of biology in general. 2) yeast are useful in their own right (see this: and this) - S. cerevisiae is my 4th favourite organism, I think. Synthesising the yeast genome will aid our exploitation of this organism, and 3) This is a stepping stone to synthetic ‘higher eukaryotic’ genomes (like us or our domestic animals) – the generation of synthetic higher animals may aid the development of new medical treatments and economic benefits. Remember where we were only a couple of years ago with mycoplasma. Whatever you want to call it.
The paper is pretty straightforward but has a lot of supplementary data (no surprise there for a Science paper), which actually covers the bulk of this work (biological characterisation) – worth a read to see if there are any downsides to synthetic genomes(!). So have fun reading. Here are a couple of discussion points for you to think about (the usually ‘is this paper written well’ also applies).
1) what do you make of the authors design principles? They screwed around a great deal with this chromosome.
2) what do you think of the biological effect of the synthetic chromosome? how much change should be tolerated?
3) what would you do with this system? They mentioned ‘scrambling’ the genome to uncover hidden biology of yeast but what else could you do?
4) how hard would a human chromosome be to generate?