Extensive alternative splicing triggered by mitonuclear mismatch in naturally introgressed Rhinolophus bats

Chen, Wenli; Mao, Xiuguang

Mitochondrial function needs strong interactions of mitochondrial and nuclear (mitonuclear) genomes, which can be disrupted by mitonuclear mismatch due to mitochondrial DNA (mtDNA) introgression between two formerly isolated populations or taxa. This mitonuclear disruption may cause severe cellular stress in mismatched individuals. Gene expression changes and alternative splicing (AS) are two important transcriptional regulations to respond to environmental or cellular stresses. We previously identified a naturally introgressed population in the intermediate horseshoe bat (Rhinolophus affinis). Individuals from this population belong to R. a. himalayanus and share almost identical nuclear genetic background; however, some of them had mtDNA from another subspecies (R. a. macrurus). With this unique natural system, we examined gene expression changes in six tissues between five mitonuclear mismatched and five matched individuals. A small number of differentially expressed genes (DEGs) were identified, and functional enrichment analysis revealed that most DEGs were related to immune response although some may be involved in response to oxidative stress. In contrast, we identified extensive AS events and alternatively spliced genes (ASGs) between mismatched and matched individuals. Functional enrichment analysis revealed that multiple ASGs were directly or indirectly associated with energy production in mitochondria which is vital for survival of organism. To our knowledge, this is the first study to examine the role of AS in responding to cellular stress caused by mitonuclear mismatch in natural populations. Our results suggest that AS may play a more important role than gene expression regulation in responding to severe environmental or cellular stresses.