Patterns of interactions could influence the biological systems at various levels and potentially affect the evolutionary history. Gene interactions could affect the relation among genotypes and their phenotypes. Polymorphisms of genes potentially alter interactions among genes, and hence, affect the fitness of individuals. Certain combinations of polymorphisms among genes can be maintained by selection. The main question of this thesis regards the effects of interactions in biological systems.

Reproductive isolation arises as a by-product of different combinations of substitutions between divergent populations. Bateson-Dobzhansky-Muller (BDM) model states fitness changes due to incompatible combinations of loci. Nonlinear rates of accumulation of incompatibilities have been proposed considering interactions among multiple loci. However, the effects of topologies of gene interaction networks (GINs) altering the rates of accumulation of incompatibilities have not been investigated.

The third topic revolves around effects of gene interactions in hybridizing species. Gene flow homogenizes the gene pool of incipient species and impedes divergence. This process can take place because incipient species either remain in spatial contact or have secondary contact through range shifts. The porous intrinsic reproductive barriers between species for loci post various properties contributing to success to move between species.

We utilized human GINs combined with single nucleotide polymorphisms (SNPs) from human HapMap to investigate the correlations between interactions and interlocus nonrandom associations of polymorphisms. To investigate the effects of gene interactions between species, we modified the “snowball effect” and simulated the rates of accumulation of incompatibilities by introducing the structure information of GINs. To profile the functional characteristics of introgressed genes, we adopted the maximum likelihood method for public genomic resources focusing on a primate hybrid zone of cynomolgus monkey (Macaca fascicularis) and rhesus monkey (M. mulatta).

Our results suggest that GINs enable global scale studies and provide polygenic insight of complex traits between and within species. Application of gene interactions ranges from enhancement of genome-wide association studies, identification of interacting polymorphisms to biomedical researches. Gene interactions also provide a platform of understanding hybridization and the dynamics of speciation.