[
International Worm Meeting,
2019]
The epistatic gene - gene interactions are quite common and they shape fitness landscape. They create multiple fitness picks and fitness valleys of that landscape but they as well allow for crossing of those valleys. By now it is known that the fitness landscape created by pairwise gene interactions can change depending on environmental conditions. Some experimental and simulation studies on single celled organisms have shown that in harsh environments epistatic interactions between deleterious genes usually are less harmful than expected from single gene effects. But is this a general rule which is true for multicellular organisms as well? In our previous experiment we have shown that it is true for epistatic interactions in Caenorhabditis elegans treated with heat shock. But how about different harsh environments? In this study we analyzed over 1000 pairwise interactions in C. elegans in each of three environments: two harsh environments and standard laboratory condition. In harsh conditions we treated worms with genotoxic agent methyl-methanesulfonate (MMS) or with oxidizing agent hydrogen peroxide (H2O2). We used high-throughput screen in liquid using bacteria consumption as a proxy of worm fitness and calculated epistatic scores (S-scores) using multiplicative model. In one of those harsh conditions (H2O2) the epistatic interactions become more suppressing (positive, mean S-score 0.29) in comparison to control conditions (mean S-score 0.08) but in the other (MMS) they did not (mean S-score 0.04). So, we did not unambiguously confirm that harsh conditions will alleviate the effect of deleterious gene via epistatic interactions. But it might be that the concentration of MMS used in our experiment was not strong enough to elicit such phenomenon. In our next experiment we plan to check the dependence of epistasis on different concentrations of MMS.
[
International Worm Meeting,
2021]
Epistasis is a phenomenon of different loci interacting with each other, ergo having non-independent effect. But even though genetic interactions are widely spread across genomes their importance is still being questioned. Depending on the perspective, epistasis is said to either play an essential role in both applied (animals and plants breeding, forensics, personalized medicine) and evolutionary biology (emergence of sex, speciation, shaping evolutionary landscapes) or to be seen as a noise of linear genes effect. In general, epistasis can be either positive, when double mutant has higher than expected fitness, or negative, when the fitness is lower than expected. Sign and reciprocal sign epistasis are peculiar cases of genetic interactions, where one or both mutations have effect opposite from both mutations combined. We have tested over 1000 pairwise interactions in standard conditions and in three different environmental stressors: heat shock (37°C), oxidative (H2O2) and mutagenic (MMS) stress. We have found that sign epistasis is a prevalent event; 40-78% of all significant interactions are in fact sign epistasis. What is even more interesting, we were able to detect few examples of reciprocal sign epistasis, however only in harsh environments; one in MMS treatment and four in H2O2 treatment. All of them were the examples of positive reciprocal sign epistasis - despite the deleterious effect of both single mutations, double mutant exhibited higher than expected fitness (higher than animals without any mutations). Both sign and reciprocal sign epistasis are a game changer when it comes to predicting fitness landscapes. As much as sign epistasis is able to slow down the process of reaching fitness optimum, reciprocal sign epistasis can actually block it, unless e.g. two mutations occur simultaneously. Our findings are notably important, since they point to the importance of considering environment in studying genetics and evolutionary scenarios.
[
International Worm Meeting,
2019]
Epistasis is a phenomenon of different loci interacting with each other. It is known for having an effect on evolution of sex and recombination, complex traits development, speciation and fitness landscape. What is more, it has been recently acknowledged for its important role in evolution of microbial drug resistance, disease diagnosis and forensic analysis. High-throughput studies on epistasis uncover new genes which might be involved in certain genetic pathways and point to the functions of studied genes. However, most such studies are performed in standard laboratory conditions, and change in the environment can drastically affect the epistatic landscape - in new environment new interactions are uncovered and some of the already known interactions are lost from the sight. Studies on how epistatic interactions are changing under different conditions are still rare, especially in multicellular organisms. Here, using RNA interference method we screened over 2000 gene-gene interactions in Caenorhabditis elegans in both standard and heat-shock conditions and calculated their interaction scores (S-scores). We found that epistasis tend to be more positive in stressful environment (mean S-score 0.032 in standard versus 0.241 in heat shock). In heat shock we discovered 79% more supressing than enhancing interactions, whereas in standard conditions we found the same amount of each. We propose that observed phenomenon might have an effect on the strength of selection, when organism is facing unfavourable environment.