Drosophila melanogaster’de Srl Geninin Egzersiz Fizyolojisi Yanıtlarını Etkileyen Genetik Elementlerin Genom Boylu İlişkilendirme Çalışması ile Saptanması

Abstract

In this thesis, it is aimed to determine the processes that affect the expression of the spargel (srl) gene, which is known to have an important role in exercise physiology, and the genes it interacts with. The srl gene, which plays a role in mitochondrial biogenesis and energy metabolism, has been shown in studies to date to affect adaptations to exercise and climbing ability performance. This thesis is a comprehensive study on the complex genetics of exercise physiology with respect to the effects of genetic background. The response to exercise was phenotyped by the effect of the change in negative geotaxis behavior of Drosophila melanogaster on its climbing ability performance. 105 DGRP strain, mutant strain with homozygous mutant allele of srl gene and control strain from which this strain was formed were used in the experiments performed within the scope of the thesis. There were statistically significant differences between the climbing ability performances of the control strain and the mutant strain by exercise status, sex and age groups. Individuals belonging to the F1 strain obtained as a result of crosses between DGRP strains, mutant strain and control strain were analyzed according to exercise status, both sexes and two age groups. When the climbing ability performance scores of F1 individuals obtained from the crosses were examined with analysis of variance, it was iv observed that the resulting differences were associated with the interaction terms Exercise x Genotype x Sex x Strain, Exercise x Genotype x Strain x Age, and the correlation was statistically highly significant (p <0.001). In the genome-wide association study (GWAS), the data obtained from the DGRP x Control strain climbing ability performance score averages, taking the differences in climbing ability performance score averages of DGRP x Mutant strain were used as GWAS input. A total of 8 GWASs were performed with meaningful combinations of exercise status, sex and age parameters in the experiment. As a result of the GWASs performed, a total of 214 Drosophila genes were identified and the orthology of these genes with 882 human genes was established in ontology analysis. 64 of these detected genes were analyzed through bioinformatics databases and it was seen that there were important genes involved in systems known to be directly related to exercise physiology. Among these genes associated with systems, all genes except the Oamb gene were first introduced to the literature as candidate genes related to exercise physiology within the scope of this thesis. It has been observed that these detected genes are associated with many diseases whose human orthologs are affected by adaptive responses to exercise. As a result, it is thought that with this thesis presented, important contributions will be made to the literature about the complex genetics of exercise physiology.