The Genetic Basis of Mutation Rate Variation in Yeast

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Joshua S. Bloom^2²  Liangke Gou^1³  Leonid Kruglyak^3⁵ 

[1] Department of Biological Chemistry, University of California, Los Angeles, California 90095^3;Department of Human Genetics, University of California, Los Angeles, California 90095;Department of Human Genetics, University of California, Los Angeles, California 90095^1;Howard Hughes Medical Institute, University of California, Los Angeles, California 90095;Howard Hughes Medical Institute, University of California, Los Angeles, California 90095^2

关键词: Spontaneous mutation rate;    QTL mapping;    genetic basis;    natural variants;    yeast;    complex traits;   

DOI  :  10.1534/genetics.118.301609

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

Mutations are the root source of genetic variation and underlie the process of evolution. Although the rates at which mutations occur vary considerably between species, little is known about differences within species, or the genetic and molecular basis of these differences. Here, we leveraged the power of the yeast Saccharomyces cerevisiae as a model system to uncover natural genetic variants that underlie variation in mutation rate. We developed a high-throughput fluctuation assay and used it to quantify mutation rates in seven natural yeast isolates and in 1040 segregant progeny from a cross between BY, a laboratory strain, and RM, a wine strain. We observed that mutation rate varies among yeast strains and is heritable ( H ² = 0.49). We performed linkage mapping in the segregants and identified four quantitative trait loci underlying mutation rate variation in the cross. We fine-mapped two quantitative trait loci to the underlying causal genes, RAD5 and MKT1 , that contribute to mutation rate variation. These genes also underlie sensitivity to the DNA-damaging agents 4NQO and MMS, suggesting a connection between spontaneous mutation rate and mutagen sensitivity.

【 授权许可】

CC BY