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The secrets of gene interactions: How to uncover the mysterious connection between genes and phenotypes?
In the biological world, genes, as the basic units of genetic information, play a vital role in the phenotype (such as appearance, behavior and physiological characteristics) of organisms. However, as our research progresses, we find that most genes do not determine a specific phenotype alone. Instead, the formation of phenotypes often depends on the interactions between multiple genes, which form an intricate network of gene interactions.
Gene interaction networks represent the functional interactions between gene pairs in an organism and are crucial for understanding the relationship between genotype and phenotype.
Studies have shown that human individuals carry approximately 4 million genetic variants and polymorphisms, most of which cannot be clearly pinpointed as a single cause of a specific phenotype. Instead, the effects of these genetic variants may be additive or even synergistic, and the contribution of each variant to a quantified trait or disease risk may depend on the genotypes of dozens of other variants. Interactions between genetic variants and environmental conditions may play an important role in determining the phenotype produced by a given genotype.
Overview of Gene Interactions
Gene interactions occur when the interaction between two or more genes results in a phenotype that differs from the phenotype expected from the independent genes. A genetic interaction is defined as “the difference between the experimentally measured double mutant phenotype and the expected double mutant phenotype based on the effects of the single mutations assuming that the mutations act independently.”
In this context, the phenotype often studied is fitness, which measures the relative reproductive rate of mutants.
Strong mutants have lower fitness levels, while weak mutants have fitness levels close to those of non-mutant strains. When the phenotype of a double mutant is stronger than expected, it is called a negative genetic interaction. Synthetic lethal interactions are a special case in which the removal of a single gene does not cause significant harm to the organism, but the removal of two genes renders the organism nonviable. On the contrary, if the phenotype of the double mutant is weaker than expected, it is called a positive genetic interaction. The special case is gene suppression, which is equivalent to the phenotype of the double mutant being weaker than the weakest single mutant.
Characteristics of gene interaction networks
Gene interaction networks have been extensively studied in a variety of organisms, including yeast, Saccharomyces cerevisiae, Escherichia coli, nematodes, and fruit flies. These studies provide insights into understanding the properties of gene interaction networks, such as their topological structure, how they provide information about gene function, and which gene interaction network features are conserved during evolution.
The key hubs of gene interaction networks are often essential proteins.
When two genes interact with similar neighbors, this can not only provide information about the relationship between the functions of the two genes, but also help understand the biological processes in which these genes are jointly involved. Gene interaction profile networks provide a powerful tool to predict the functions of uncharacterized genes. Some studies have also explored the conservation of gene networks over evolutionary distances. Although it is unclear whether interactions between individual genes are conserved, general properties of gene interaction networks appear to be conserved, such as hubs in the network and the ability of gene interaction profiles to predict biological function.
Biological significance
Gene interactions are important in linking genotypes to phenotypes. For example, they have been proposed as an explanation for genetic deletions. Missing heritability means that the genetic sources of many heritable phenotypes have not yet been discovered. Although many hypothetical explanations have been proposed, genetic interactions may significantly reduce the number of missing genetic mechanisms by increasing the explanatory power of known genetic sources. These gene interactions may go beyond the pairwise interactions considered in the gene interaction network.
As research deepens, the complexity of gene interactions gradually reveals its hidden importance. Understanding how these interactions will affect our understanding of diseases and phenotypes may change the direction of our treatment and prevention strategies. Have we reached the point where we are revealing the true potential of genetic interaction networks?
