Zhu, Z., Lu, Q., Yuan, D., Li, Y., Man, X., Zhu, Y., and Huang, S. (2013) Role of genetic polymorphisms in transgenerational inheritance of inherent as well as acquired traits in budding yeast. arXiv:1302.7276 [q-bio.GN]， submitted. pdf
Role of genetic polymorphisms in transgenerational inheritance of inherent as well as acquired traits in budding yeast
Zuobin Zhu, Qing Lu，Dejian Yuan，Yanke Li，Xian Man，Yueran Zhu， and Shi Huang*
State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, P.R. China
Both inherent and acquired traits can be transmitted through multiple generations with some traits more stable than others. But the relationship between the stability of such transgenerational inheritance and the genetic variations in an individual or cell has yet to be explored. We studied the effect of common genetic polymorphisms on transgenerational inheritance of yeast segregants that were derived from a cross between a laboratory strain and a wild strain of Saccharomyces cerevisiae. For each of 2835 common SNPs analyzed, the parental allele present in less than half of the 124 segregants panel was called the minor allele (MA). We found a nonrandom distribution of MAs in the segregants, indicating natural selection, as segregants with high MA content or amount (MAC) were not enriched with MAs from the parental strain that contributed significantly more to the whole set of MAs. We compared segregants with high 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. Sodium chloride treatment produced similar observations. Using public datasets, we found MAC linkage to mRNA expression of hundreds of genes. Finally, by analyzing a recently published datasets of 1009 yeast segregants that identified numerous additive QTLs for 46 traits, we found by multivariate regression analysis preferential effect of MAC on traits with high number of known additive QTLs (average 16 QTLs for the 5 MAC-linked traits vs 12 for the whole set of 46 traits), consistent with an additive effect of a large number of SNPs or MAs whose individual effect would be too minor to be detectable by existing methods. These results provide evidence for the slightly deleterious nature of most MAs and a lower capacity to maintain inheritance of traits in individuals or cells with greater MAC, which have implications for disease prevention and treatment. Individuals with high MAC may be more susceptible to environmental pathogens, but they may also be more treatable if treatment was administered relatively early before the disease has progressed past the threshold of no return, because the acquired disease trait may be less stably maintained in these individuals. The concept and method of MAC are broadly applicable, and may have solved a large part of the “missing heritability” problem in complex traits by simply relying on a priori truth/intuition that no mutation can be truly neutral or devoid of an entropy generating effect.