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Genome-wide comparison of artificially induced mutations and natural variations in Brachypodium distachyon


Authors:
Li Lei 1; Joel Martin 1; Mingqin Shao Shao 1; Jie Guo 1; Amy Cartwright 1; Jeremy Philips 1; Lesly Fang 1,2; Jacob Espinosa 1,2; Corey Carter 4; Skylar Wyant 4; Chaochih Liu 4; Peter Morrell 4; David Goodstein 1; Richard Sibout 5; Debbie Laudencia-Chingcuanco5 3; John Vogel 1,6

Affiliations:
1) DOE Joint Genome Institute; 2) The University of California, Merced, CA; 3) USDA-ARS Western Regional Research Center, Albany, CA, USA; 4) Department of Agronomy and Plant Genetics, University of Minnesota, St. Paul, MN USA 55108; 5) Institut Jean-Pierre Bourgin, INRAE, AgroParisTech, Université Paris-Saclay, 78000, Versailles, France; 6) UC Berkeley Department of Plant and Microbial Biology, Berkeley, CA, USA

Keywords:
Molecular Evolution

Natural variation has been extensively used during the domestication and improvement of plants and animals. However, the spectrum of polymorphisms present in natural variation is limited due to the low spontaneous mutation rate (5.9 - 7 x 10-9 per base pair per generation) and natural selection against variants that may be beneficial in an agricultural setting but deleterious in a natural environment. To overcome these limitations, artificially induced mutations have been to accelerate the development of improved cultivars. However, the nature of specific mutations induced the molecular and physiological basis for the improved characteristics in the varieties has been poorly understood.[vv1] In this study, we created a powerful reverse and forward genetic tool by sequencing a collection of 2,000 chemical and radiation mutants in the model grass B. distachyon. In total, we identified ~2 million mutations and predicted which mutations, including nonsynonymous mutations, may alter protein function. We also compared the induced mutations with the natural variation from 116 diverse B. distachyon lines. The[vv2] chemical mutagens ethyl methanesulfonate and sodium azide tend to induce more transition mutations, particularly C->T or G ->A transitions than radiation and natural variation. Furthermore, induced mutations are predicted to alter protein function (with a higher proportion of deleterious mutations) than natural polymorphisms. We used a pan-genomic approach to determine that induced mutations induce deleterious mutations evenly in all genes whereas potentially deleterious natural variants are less likely to occur in conserved (core) genes than in variable genes. By predicting the potential deleterious effects of nonsynonymous mutations we increased the utility of the mutation collection to study all aspects of grass biology.