Whole-genome profiling of mutagenesis in Caenorhabditis elegans.
Deep sequencing offers an unprecedented view of an organism's genome. We describe the spectrum of mutations induced by three commonly used mutagens: ethyl methanesulfonate (EMS), N-ethyl-N-nitrosourea (ENU), and ultraviolet trimethylpsoralen (UV/TMP) in the nematode Caenorhabditis elegans. Our analysis confirms the strong GC to AT transition bias of EMS. We found that ENU mainly produces A to T and T to A transversions, but also all possible transitions. We found no bias for any specific transition or transversion in the spectrum of UV/TMP-induced mutations. In 10 mutagenized strains we identified 2723 variants, of which 508 are expected to alter or disrupt gene function, including 21 nonsense mutations and 10 mutations predicted to affect mRNA splicing. This translates to an average of 50 informative mutations per strain. We also present evidence of genetic drift among laboratory wild-type strains derived from the Bristol N2 strain. We make several suggestions for best practice using massively parallel short read sequencing to ensure mutation detection.
Flibotte
Stephane
S
Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Edgley
Mark L
ML
Chaudhry
Iasha
I
Taylor
Jon
J
Neil
Sarah E
SE
Rogula
Aleksandra
A
Zapf
Rick
R
Hirst
Martin
M
Butterfield
Yaron
Y
Jones
Steven J
SJ
Marra
Marco A
MA
Barstead
Robert J
RJ
Moerman
Donald G
DG
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D005020:Ethyl Methanesulfonate; D005038:Ethylnitrosourea; D016678:Genome; D016296:Mutagenesis; D009153:Mutagens; D009154:Mutation; D010641:Phenotype; D014307:Trioxsalen
D009153:Mutagens; D005020:Ethyl Methanesulfonate; D005038:Ethylnitrosourea; D014307:Trioxsalen