Bai Fengyan’s team from the Institute of Microbiology of the Chinese Academy of Sciences reveals the molecular mechanism of hybrid vigor in Saccharomyces cerevisiae
By: Date: 2021-04-03 Categories: foodtechnology Tags: ,
   Hybrid advantage is a common biological phenomenon, and is widely used in the breeding of animals, plants and edible fungi, which contributes to the continuous increase in the production of global agriculture and animal husbandry. huge contribution. Hybrid vigour has always been a major subject of scientific research. Since Darwin first observed this phenomenon, research on the genetics and molecular mechanisms of hybrid vigour has been going on for nearly a century and a half, and various hypotheses have been proposed, including dominant ( Dominance, overdominance, epistasis, etc., each hypothesis has its own experimental evidence to support. In order to unify different hypotheses and viewpoints, some people have proposed the energy utilization efficiency hypothesis, but this hypothesis is limited to theoretical inference and lacks experimental evidence to support it.

   Saccharomyces cerevisiae (Saccharomyces cerevisiae), as the most commonly used model eukaryote, has also been increasingly used in the study of the genetic and molecular mechanisms of hybrid vigor. But different studies have reached different conclusions. Early research by Bai Fengyan’s team at the State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, found that the wild populations of Saccharomyces cerevisiae are all homozygous, while the domesticated populations from the fermentation environment are all heterozygotes. The fermentation and stress resistance of the domesticated population have been significantly improved, indicating that the domesticated population may have originated from heterozygous ancestors formed by the hybridization of wild strains, thus obtaining hybrid vigor. In order to verify whether the hybridization of wild strains can produce hybrid vigor and reveal the molecular mechanism of hybrid vigor, this study obtained more than 640 heterozygotes formed by hybridization of wild strains with different genetic distances. It was found that at 40°C, the vast majority Heterozygotes showed significant hybridization, and only a few showed hybridization disadvantages. Hybrid vigor increases with the increase of parent genetic distance, but after a certain distance, it shows a downward trend, indicating that there is an optimal genetic distance between parents that produces hybrid vigor (Figure 1).
Bai Fengyan’s team from the Institute of Microbiology of the Chinese Academy of Sciences reveals the molecular mechanism of hybrid vigor in Saccharomyces cerevisiaeimage
   Figure 1. Wild Saccharomyces cerevisiae F1 heterozygote 40 The relationship between hybrid vigor (A, B) and genetic distance between parents (C) for growth at °C.

   represents heterozygous and parental transcriptome analysis shows that although the number of non-overlapping genes (NAG) is relatively small compared with the number of overlapping genes (NA), but in the superiority and There are significant differences between disadvantaged heterozygotes. NAG whose expression level is up-regulated in the dominant heterozygote is down-regulated in the inferior heterozygote, and vice versa (Figure 2). The number of down-regulated NAGs in the dominant heterozygotes was significantly higher than the number of up-regulated NAGs, but the opposite was true in the inferior heterozygotes. It shows that these NAGs are related to hybrid vigor.
Bai Fengyan’s team from the Institute of Microbiology of the Chinese Academy of Sciences reveals the molecular mechanism of hybrid vigor in Saccharomyces cerevisiaeimage(1)< br/>
  Figure 2. The wild strain of Saccharomyces cerevisiae is heterozygous at 40 The expression level of non-overlapping genes when growing at °C (A), GO enrichment analysis (B, D) and enrichment pathway network (C, E).

   GO and KEGG analysis found that NAGs that are down-regulated in dominant heterozygotes and up-regulated in disadvantaged heterozygotes are mostly enriched in response to stress and DNA repair In the pathways related to protein quality control, it shows that inferior heterozygotes need to deal more with DNA damage and protein synthesis and folding errors caused by high temperature stress, while high temperature did not cause these damages to dominant heterozygotes. NAGs that are up-regulated in dominant heterozygotes and down-regulated in inferior heterozygotes are mostly enriched in one-carbon metabolism and related pathways (Figure 2). These pathways are related to the production of NADPH and the maintenance of the reduced state, indicating that the hybrid dominant strains can more efficiently deal with the oxidative stress caused by high temperature, while the inferior strains are not.

   ROS level test confirmed that ROS in dominant heterozygous cells was significantly lower than inferior heterozygous and parents. Knockout of the key genes ADE3 or MTD1 in the one-carbon metabolic pathway can lead to a significant increase in the ROS level and NADP+/NADPH ratio of the dominant heterozygote at 40°C and a significant reduction in the growth ability. Adding the ROS scavenger N-acetyl-L-cysteine ​​can restore the growth ability of the knockout strain at 40°C, and can also promote the growth ability of the inferior heterozygous and parent strains, while the dominant heterozygous wild-type There is no effect or even a negative effect (Figure 3). It shows that the difference in the efficiency of coping with oxidative stress is the key factor that causes the difference in the growth ability of the superior and inferior heterozygote and its parent strain under high temperature.
Bai Fengyan’s team from the Institute of Microbiology of the Chinese Academy of Sciences reveals the molecular mechanism of hybrid vigor in Saccharomyces cerevisiaeimage(2)< br/>
  Figure 3. ADE3 knockout pair heterozygotes The influence of growth ability (A, B) and intracellular oxidative pressure (C) at 40°C.

   In short, this study shows that hybridization of wild Saccharomyces cerevisiae strains with suitable genetic distance can produce significant hybridization, and dominant heterozygotes can regulate gene expression more efficiently. Under high temperature stress, the relevant metabolic pathways centered on one-carbon metabolism can be upregulated to effectively maintain cell redox homeostasis, thereby maintaining normal cell growth. Compared with parental and inferior heterozygotes, dominant heterozygotes also show higher energy utilization efficiency because they do not need to up-regulate a large number of genes to deal with DNA and protein damage and other damages caused by oxidative stress. This study reveals the new molecular mechanism of hybrid vigor and high temperature tolerance in Saccharomyces cerevisiae, and also provides new enlightenment and clues for the study of the molecular mechanism of hybrid vigor in animals and plants.

   The topic of this research is”Improvedredox homeostasis owing to the upregulation of one-carbon metabolism and related pathways is crucial for yeast heterosis at high temperature”. It will be officially published on Genome Research on April 1, 2021. The co-first authors of the thesis are PhD students Song Liang and Shi Junyan, and the corresponding authors are researcher Bai Fengyan. This research was funded by the Key Frontier Science Research Project of the Chinese Academy of Sciences and the International Cooperation Project of the Ministry of Science and Technology.

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