Effects Of Mitochondrial And Nuclear Interactions On Nuclear Gene Expression In Natural Bat Populations

Mitochondrial function depends on strong interaction of both mitochondrial and nuclear genomes.Selection for this strong mitonuclear interaction can lead to co-evolution of mitonuclear genomes which results in co-adapted mitonuclear genotypes in different isolated taxa or species.However,when formerly isolated taxa or species come into secondary contact,introgression of mitochondrial DNA between them will lead to mitonuclear mismatched genotypes in introgressed individuals.Previous studies have shown that disruption of mitonuclear interaction（mitonuclear mismatch）can affect nuclear gene expression in several model systems（e.g.Drosophila and mice）.However,few such studies have been conducted in naturally introgressed populations.Here we fill this gap by studying a naturally introgressed population of the intermediate horseshoe bat（Rhinolophus affinis）.We sampled one R.a.himalayanus population which includes individuals with either mitonuclear matched or mismatched genotypes.For each individual,we generated transcriptome data in six adult tissues.With these RNA-seq data,we assess transcriptional variations of nuclear genes between mitonuclear mismatched and matched individuals.First,this study performed principal component analysis and F_ST analysis based on sequence data of mitochondrial and nuclear genomes from all R.a.himalayanus individuals.The results showed that all 10 individuals had almost identical nuclear genetic background,whereas half of individuals had R.a.macrurus mitogenome.Thus,this population can be divided into two groups:mitonuclear mismatched and matched groups.There are 14 amino acid changes in mitochondrial protein-coded genes between individuals of these two groups.Second,we performed differential expression analysis between individuals of mitonuclear mismatched and matched groups in each of the six tissues.（1）We found profound and tissue-specific effects of changes in nuclear gene expression.A total of 60 differentially expressed genes（DEGs）were identified across all tissues.Specifically,among these six tissues,muscle showed the largest number with 43 DEGs,and the remaining tissues each showed fewer than 10（2 in heart tissue,2 in brain tissue,7 in liver tissue,3 in cochlear tissue and 3 in gut tissue）.No overlapped DEGs were found across tissues.（2）Several upregulated DEGs in mismatched individuals,such as DNASE1L3,GPx3,and HSPB6 in muscle,ISG15 and IFI6 in heart,CYP26A1 in brain,and CA3 and NMRAL1 in gut,showed protective roles against oxidative stress.Finally,functional enrichment analysis on 43 DEGs identified in muscle tissue showed that most of them are related to immune response including cell killing,positive regulation of cytokine production,lymphocyte activation,leukocyte proliferation,and interferon-gamma production.We also found terms associated with actin-myosin filament sliding and calcium ion transport.In contrast to muscle,we did not find any significant GO terms among DEGs identified in the other five tissues examined.Our current study indicates that we can indirectly assess the effects of mitonuclear mismatch on organisms by examining changes of nuclear gene expression in multiple tissues.Underlying the processes that maintain mitonuclear mismatch in nature will help to understand the role of mitonuclear interaction in population divergence and speciation.