Inferring multilayer interactome networks shaping phenotypic plasticity and evolution

Abstract

Phenotypic plasticity represents a capacity by which the organism changes its phenotypes in response to environmental stimuli. Despite its pivotal role in adaptive evolution, how phenotypic plasticity is genetically controlled remains elusive. Here, we develop a unified framework for coalescing all single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) into a quantitative graph. This framework integrates functional genetic mapping, evolutionary game theory, and predator-prey theory to decompose the net genetic effect of each SNP into its independent and dependent components. The independent effect arises from the intrinsic capacity of a SNP, only expressed when it is in isolation, whereas the dependent effect results from the extrinsic influence of other SNPs. The dependent effect is conceptually beyond the traditional definition of epistasis by not only characterizing the strength of epistasis but also capturing the bi-causality of epistasis and the sign of the causality. We implement functional clustering and variable selection to infer multilayer, sparse, and multiplex interactome networks from any dimension of genetic data. We design and conduct two GWAS experiments using Staphylococcus aureus, aimed to test the genetic mechanisms underlying the phenotypic plasticity of this species to vancomycin exposure and Escherichia coli coexistence. We reconstruct the two most comprehensive genetic networks for abiotic and biotic phenotypic plasticity. Pathway analysis shows that SNP-SNP epistasis for phenotypic plasticity can be annotated to protein-protein interactions through coding genes. Our model can unveil the regulatory mechanisms of significant loci and excavate missing heritability from some insignificant loci. Our multilayer genetic networks provide a systems tool for dissecting environment-induced evolution.

Characterization, costs, cues and future perspectives of phenotypic plasticity

“…Recently, a framework has been proposed to study the genetic basis of phenotypic plasticity and highlights quantitative genetics and gene hub approaches ( Laitinen and Nikoloski, 2019 ). Furthermore, approaches have been developed that integrate genetic mapping, evolutionary game theory and predator–prey theory ( Yang et al , 2021 ).…”

Reaction Mechanisms for Chiral-Phosphate-Catalyzed Transformations Involving Cationic Intermediates and Protic Nucleophiles

“…85 More recently, Yang and coworkers proposed that the interaction between iminiums generated from allenamides and the catalyst is ionic. 86 However, theoretical work suggested that double coordination modes are much more likely. 53,67 Accordingly, we considered that the mechanism could also proceed through establishing two H-bonding interactions between the chiral phosphate and the reactants.…”

“…reported the enantioselective addition of -alkynyl ketones to allenamides. 86 Using our previous computational work on this reaction class, we can confidently analyze the steric demands on the nucleophile and determine that sp 3 substituents will likely be bulkier than sp 2 and sp substituents. Accordingly, we can expect the nucleophile will fit into the chiral pocket similar to that shown for model 3.…”

Metabolomics for Crop Breeding: General Considerations

“…Epistasis was suggested as an explanation of missing heritability [19]. The idea of epistasis was extended in the omnigenic theory, which states that complex traits are controlled by all genes of the organism [20].…”

“…Increasing the number of lines by a factor of 10-100 would be a difficult task. In another work, the number of samples for determining the interaction of only two genes using GWAS is estimated at 10,000 while there are millions of millions of gene pairs [20]. It can be summarized that currently, we do not have adequate tools to comprehensively evaluate the epistasis [21].…”