M. Costanzo et al., “The genetic landscape of a cell,” Science, 327:425–31, 2010. http://bit.ly/genlandscape
Knocking out a single gene in yeast often has little effect; yeast can survive with only about 20% of their 6,000 genes intact and researchers often need to knock out a second gene at random to determine function. Now, a network map of over 5 million such double mutants makes it possible to predict the function of 75% of the yeast genome.
To measure the effects of double mutants, the researchers, coordinated by Charles Boone at the University of Toronto, looked at the size of yeast colonies. Very small colonies indicated that the genes were closely related or essential to the same pathway, while slightly larger colonies signified...
The work is “a veritable tour de force that gives the most comprehensive insight to date” into functional genetic interactions, writes Faculty Member Jurg Bahler. The network “map” shows which genes are functionally related, and allowed the authors to predict the function of several previously uncharacterized genes— that they later confirmed by biological studies.
The next step
“The ultimate goal is to test all pair-wise combinations” to create a global “wiring diagram” of the yeast cell, Boone says. To reveal the function of the missing interactions, he also wants to test yeast under different growth conditions, and is keen to see a similar map in other animals, and eventually humans.
F1000 evaluators: E. de Nadal and F. Posas (Univ. Pompeu Fabra) • J. Bahler (Univ. College London) • N. P. Tatonetti and R. Altman (Stanford Univ.) • J. Snider and I. Stagljar (Univ. of Toronto)