Regulatory Subfunctionalization drives OXPHOS evolution in teleosts

Abstract

Oxidative phosphorylation (OXPHOS) supplies over 90% of the cellular ATP requirements through the orchestrated function of five multiprotein complexes located in the inner mitochondrial membrane. The study explores how the evolutionary constraints imposed by the indispensable function of OXPHOS guide the outcome of Whole Genome Duplication (WGD) events. Two teleosts, the gilthead seabream (Sparus aurata) and the European seabass (Dicentrarchus labrax), which have undergone three rounds of WGDs were used as models and OXPHOS gene expression was assessed during the highly plastic and energy-demanding period of early development. Fish ontogeny is a unique period in fish life marked with dramatic changes in morphology, physiology, metabolism and behavior. The tightly regulated landscape of cell divisions, migrations and differentiation driving these dramatic changes demands high energy supplies. The discovery of 24 and 22 OXPHOS gene families in gilthead seabream and European seabass genome, respectively, and the subsequent phylogenetic analysis showed in most cases divergence from a common ancestor at the base of the teleost lineage, a process attributed to teleost-specific WGD. Overall results indicate that the WGD events have resulted in early retention of OXPHOS paralogue genes and subsequent species- or lineage-specific losses. OXPHOS paralogue gene expression levels were compared following RNA sequencing within and between distinct developmental stages in gilthead seabream and European seabass. Different expression patterns between paralogs were revealed; some were in dosage balance, others were expressed only in particular stage(s) and a lot of them were differentially expressed between stages. Differences in both the number and location of SNPs were revealed between paralogs, after merging the RNA sequencing data with whole genome sequencing data. A considerable number of mutations were mapped in the UTRs and mostly synonymous substitutions were identified in the CDS. The ratio of non-synonymous to synonymous substitutions when comparing the CDS variants revealed neutral positions while others are subject to purifying selection, safeguarding protein structural integrity and/or function. Overall, regulatory subfunctionalization of OXPHOS paralogs appeared as the evolutionary mechanism behind the retention of the paralogs in gilthead seabream and European seabass genomes in favor of ontogenetic plasticity.