superpopov/iStockphoto/Getty ,

14 www.nature.com/nrg

as (2016) Nat. Rev. Genet. Rev. Nat. Darren J. Burgess J. Darren YJR141W . A global genetic . d et al . Integrative approaches for approaches . Integrative e v r e et al s e r

s t h Costanzo, M. Mitra, K. Mitra, g i r

l l A

. e r u t a http://dx.doi.org/10.1126/science.aaf1420 RESEARCH HIGHLIGHTS RESEARCH

N ) based on its genetic interaction similarity to ) based on its genetic interaction

r e The team studied the implications of positive were functional relationships By contrast, on a single phenotypic Despite the reliance Reflecting important and non-redundant Reflecting important and non-redundant g n ORIGINAL ARTICLE of cellular function. network maps a wiring diagram interaction Science READING FURTHER in biological networks. finding modular structure 719–732 (2013) i IPA1 r readout of growth rate, this study identifies rich rate, of growth readout functional information and should serve as a for further mining. valuable resource scaffold of the overall global genetic network. global genetic scaffold of the overall hub genes in the global genetic generally, More with expressed also typically highly network were and high connectivity also in protein–protein chemical-genetic networks. A prevailing versus negative genetic interactions. genetic of gene pairs with negative characteristic in a operate was that their products interactions complex. In or protein biological process shared may these cases, the negative genetic interaction that or process complex arise because the overall these genes contribute to suffers only mild impairment following loss of function of single impairment is synergistic components, but there and substantial fitness consequences in the double mutant. distant between genes displaying positive more which is consistent genetic interactions, or compensatory regulatory with broader example, diverse detrimental For relationships. mutations could be compensated by mutations in subunits (to buffer proteotoxic chaperone protein effects) or in cell cycle machinery (which mask time for the defects and/or provide the growth cellular defect to be repaired). uncharacterized essential gene uncharacterized and polyadenylation 1important for cleavage ( other mRNA cleavage and polyadenylation factors. functions, essential genes had approximately than genetic interactions fivefold more non-essential genes and formed the major p S

f o

t

r

a p

,

d

e

t i m i L

s r e h s i l b u P

n a l l i m 10.1038/nrg.2016.136 c a Saccharomyces cerevisiae Saccharomyces M

6 1 0 . used 2 layered map of cellular function. ­layered

© et al genes) were combined into a library combined into a library genes) were The catalogue of genetic interactions enabled The catalogue of genetic interactions and broad This information on both fine-grained Using growth rate as a measure of fitness, as a measure rate Using growth Costanzo GENETIC SCREENS aspects of gene function can be leveraged to infer aspects of gene function can be leveraged genes. For functions of poorly characterized the previously example, the authors renamed the construction of a functional map of the cell. to Assembling genes into clusters according profiles of similarity of interaction the degree functions. Genes were hierarchical revealed with those for which the most closely clustered focused pathways or share encoded proteins complexes. Zooming out, macromolecular together into broader the clusters grouped or such as vesicle trafficking ‘bioprocesses’ into further grouped cytokinesis, and these were cellular compartments in which these the overall occur. processes S. cerevisiae To of >23 million double-mutant strains. mutants, lethality for essential-gene circumvent allele strains they used temperature-sensitive at semi-permissive temperatures. grown the authors identified genetic interactions on the basis of whether the fitness of the double from what is expected mutant deviated from multiplicative effects of the single mutants. genetic they identified ~550,000 negative Overall, (fitness lower than expected) and interactions (fitness ~350,000 positive genetic interactions than expected). greater gene roles and interdependencies, but interdependencies, and gene roles a major undertaking studies are comprehensive owing to the combinatorial complexity of pairwise double mutants for each generating study tested. A new large-scale interaction to analyses >23 million double-mutant yeast strains a multi generate in which technology, synthetic genetic array a to generate crossed of single mutants are libraries have been Such approaches double-mutant library. the smaller scale, but here on a reported previously investigation investigators sought a comprehensive 5,416 genes (>90% of Overall, of interactions. A global map of genetic interactions A global map between genes can reveal interactions Functional Published online 14 Oct 2016; doi: online 14 Published |

GENETICS

| NATURE REVIEWS NATURE Nature Reviews Genetics Nature