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Hybrid vigor is a common biological phenomenon, and is widely used in the breeding of animals, plants and edible fungi, and has made a great contribution to the continuous increase of global agriculture and animal husbandry.
Hybrid vigor has always been a major subject of scientific research.
Since Darwin first observed this phenomenon, research on the genetics and molecular mechanisms of hybrid vigor has been going on for nearly a century and a half, and various hypotheses have been proposed, including dominant ( Dominance, overdominance and 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, 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 vigour 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 to produce hybrid vigour (Figure 1).
Figure 1.
The hybrid vigour (A, B) and the relationship between hybrid vigour and parental genetic distance (C) of heterozygous F1 generation of wild Saccharomyces cerevisiae grown at 40°C.
Transcriptome analysis on behalf of heterozygotes and parents showed that although the number of non-overlapping genes (NAG) is very small compared to the number of overlapping genes (NA), there are significant differences between dominant and inferior heterozygotes, and the expression level in dominant heterozygotes is The up-regulated NAG is down-regulated in inferior heterozygotes, 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.
Figure 2.
Non-overlapping gene expression levels (A), GO enrichment analysis (B, D) and enrichment pathway network (C, E) of heterozygotes of wild Saccharomyces cerevisiae strains grown at 40°C.
GO and KEGG analysis found that NAGs that are down-regulated in dominant heterozygotes and up-regulated in inferior heterozygotes are mostly enriched in pathways related to stress response, DNA repair and protein quality control, indicating that inferior heterozygotes need more Deal with DNA damage and protein synthesis and folding errors caused by high temperature stress, but high temperature did not cause these damages to the dominant heterozygote.
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 cellular ROS level and NADP+/NADPH ratio and a significant decrease in growth ability of dominant heterozygotes at 40°C.
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 heterozygotes and their parent strains under high temperature.
Figure 3.
The effect of ADE3 gene knockout on the growth ability (A, B) and intracellular oxidative stress (C) of heterozygotes at 40°C.
In conclusion, this study shows that hybridization of wild Saccharomyces cerevisiae strains with appropriate genetic distance can produce significant hybridization advantage, dominant heterozygotes can regulate gene expression more efficiently, and can upregulate related metabolic pathways centered on one-carbon metabolism under high temperature stress.
, Effectively maintain the cell redox homeostasis, so as to maintain the normal growth of cells.
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 other damages caused by DNA and protein damage and 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 research is titled "Improvedredox homeostasis owing to the upregulation of one-carbon metabolism and related pathways is crucial for yeast heterosis at high temperature" and was officially published in 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.
Original link: https://genome.
cshlp.
org/content/31/4/622.
full.
pdf+html
Hybrid vigor has always been a major subject of scientific research.
Since Darwin first observed this phenomenon, research on the genetics and molecular mechanisms of hybrid vigor has been going on for nearly a century and a half, and various hypotheses have been proposed, including dominant ( Dominance, overdominance and 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, 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 vigour 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 to produce hybrid vigour (Figure 1).
Figure 1.
The hybrid vigour (A, B) and the relationship between hybrid vigour and parental genetic distance (C) of heterozygous F1 generation of wild Saccharomyces cerevisiae grown at 40°C.
Transcriptome analysis on behalf of heterozygotes and parents showed that although the number of non-overlapping genes (NAG) is very small compared to the number of overlapping genes (NA), there are significant differences between dominant and inferior heterozygotes, and the expression level in dominant heterozygotes is The up-regulated NAG is down-regulated in inferior heterozygotes, 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.
Figure 2.
Non-overlapping gene expression levels (A), GO enrichment analysis (B, D) and enrichment pathway network (C, E) of heterozygotes of wild Saccharomyces cerevisiae strains grown at 40°C.
GO and KEGG analysis found that NAGs that are down-regulated in dominant heterozygotes and up-regulated in inferior heterozygotes are mostly enriched in pathways related to stress response, DNA repair and protein quality control, indicating that inferior heterozygotes need more Deal with DNA damage and protein synthesis and folding errors caused by high temperature stress, but high temperature did not cause these damages to the dominant heterozygote.
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 cellular ROS level and NADP+/NADPH ratio and a significant decrease in growth ability of dominant heterozygotes at 40°C.
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 heterozygotes and their parent strains under high temperature.
Figure 3.
The effect of ADE3 gene knockout on the growth ability (A, B) and intracellular oxidative stress (C) of heterozygotes at 40°C.
In conclusion, this study shows that hybridization of wild Saccharomyces cerevisiae strains with appropriate genetic distance can produce significant hybridization advantage, dominant heterozygotes can regulate gene expression more efficiently, and can upregulate related metabolic pathways centered on one-carbon metabolism under high temperature stress.
, Effectively maintain the cell redox homeostasis, so as to maintain the normal growth of cells.
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 other damages caused by DNA and protein damage and 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 research is titled "Improvedredox homeostasis owing to the upregulation of one-carbon metabolism and related pathways is crucial for yeast heterosis at high temperature" and was officially published in 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.
Original link: https://genome.
cshlp.
org/content/31/4/622.
full.
pdf+html
