Wheat (Triticum aestivum) possesses the largest set of available alloplasmic lines in either the plant or animal kingdom. These alloplasmic lines consist of novel combinations of wheat cultivar nuclei and cytoplasm, derived from the Triticum and Aegilops genus. This set of alloplasmic lines provides a unique genetic resource for the enhancement of existing germplasm. The current study was devised to address several aspects of cytoplasm genetics, including cytoplasm evolution and its interaction with the nuclear genome. Initially, the ATP6 gene from 46 different alloplasmic lines was isolated and sequenced. ATP6 resides on the mitochondrial genome, and its function involves the electron transfer chain in the mitochondrial inner membrane. Our results revealed the existence of vast diversity among the cytoplasms. Two novel orthologs of ATP6-1 genes were detected in our analysis. Subsequently, the expression activity of these orthologs was confirmed by RT-PCR. In the second part of this research, an integrative approach was employed to more elucidate the mechanism of nuclear-cytoplasmic interaction. For this study, wheat alloplasmic lines possessing Ae. mutica cytoplasm were compared with their corresponding euplasmic lines. Comparative QTL analysis for dry matter weight, height and spike number per plant was conducted to identify QTL which interact with each cytoplasm type. As a result, a QTL hotspot was detected on chromosome 5A. Furthermore, this analysis revealed that the genetic network, controlling traits, is dynamic. The genetic network is affected by the cytoplasm type. The methylation pattern of nuclear genes was shown to be influenced by cytoplasm. Sequencing revealed that the majority of the identified epialleles located within genic regions. Finally, this alteration of methylation was shown to change the expression pattern of corresponding genes between allo- and euplasmic lines.