A comparative approach to discover the genomic determinants of natural adaptations to a sugar-rich diet in nectarivorous birds

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Excessive consumption of glucose- and fructose-sweetened soft drinks is a major risk factor for type 2 diabetes in humans. While a sugar-rich diet has adverse consequences on human health, several long-lived bird species that consume predominantly nectar are well-adapted to such a sugar-rich diet. This raises a fundamental question: What are the genes that are important for natural adaptations to a sugar-rich diet in these nectarivorous birds? To address this question, this proposal will combine genome sequencing and assembly, comparative genomic analysis and comparative transcriptomics. First, we will generate high-quality genome assemblies and comparative transcriptome data for strategically-selected, independent nectarivorous birds and their respective non-nectarivorous sister species. Second, building on established comparative genomics approaches, we will use the generated data to comprehensively search genes for mutational gain and loss of function signatures that occurred specifically in nectarivores, and thus uncover the genes that are likely important for natural adaptations to a sugar-rich diet. Third, we will investigate the extent of convergent molecular evolution at different hierarchical levels by genomic comparisons between three independent nectarivorous bird lineages. In contrast to genome-wide association studies that uncovered genomic loci associated with an increased risk for type 2 diabetes in humans, we will compare well-adapted nectarivorous bird species to uncover differences in genes that may confer protection to a sugar-rich diet. Ultimately, these genes could expose new risk factors and could provide new drug targets for metabolic disease, thus may have human relevance in the long-term.