Role of genetic polymorphisms in transgenerational inheritance in budding yeast

We studied the effect of single nucleotide polymorphisms (SNPs) on transgenerational inheritance of yeast segregants that were derived from a cross between a laboratory strain and a wild strain of Saccharomyces cerevisiae. We compared segregants with high minor allele content (MAC) relative to those with less and found a more dramatic shortening of the lag phase length for the high MAC group in response to 14 days of ethanol training. Also, the short lag phase as acquired and epigenetically memorized by ethanol training was more dramatically lost after 7 days of recovery in ethanol free medium for the high MAC group. We also found MAC linkage to mRNA expression of hundreds of genes and a preferential effect of MAC on traits with high number of known additive quantitative trait loci (QTLs). The study may help explain human variations in disease susceptibility and the missing heritability problem in complex traits/diseases. LMAC: low minor allele content QTL： quantitative trait loci 3 Different cell types of an individual organism carry the same DNA but manifest different traits or functions due to different epigenetic programing. A cell or organism may also acquire new traits by way of epigenetic reprograming through interaction with the environment. It is well established that both inherent traits and acquired traits can be transmitted through multiple generations with some traits more stable than others 1,2. But the relationship between the stability of such transgenerational inheritance and the degree of genetic variations in an individual or cell has yet to be explored. Also unknown is the relationship between genetic variations and sensitivity to environmental factors. Better understanding of such relationships may help explain the well-known variations in disease susceptibility in human individuals when exposed to the same environmental pathogenic factors. We here asked whether excess genetic variations can affect the transgenrational epigenetic inheritance of a trait in responses to environmental factors. We used a panel of 124 yeast segregants derived from a cross between a laboratory strain BY4716 and a vineyard isolate RM11-1a of Saccharomyces cerevisiae. Each segregant is homozygous in nearly all SNPs and the study here used a panel of 2956 SNPs previously genotyped for these segregants 3,4. For a given panel of segregants, we called minor alleles (MAs) as those parental alleles that were carried by less than half of the strains in the panel. The strains would differ in the contents of MAs that each carries, and …