Identification and functional characterisation of environmentally responsive rDNA variants in the human genome

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Mammalian phenotypes are influenced by the interaction between genetics and environment. Understanding how these gene-environment interactions occur at the level of the cell is therefore crucial for elucidating the origins of mammalian phenotypes. Recently, my team found that providing mice with a reduced protein diet during early life results in reduced overall body size which is correlated with reduced activity of the ribosomal DNA (rDNA). The rDNA is an important part of the genome that codes for molecules required for protein synthesis, thereby permitting cell growth. The most surprising finding of our study was that the genetic sequence of the rDNA varied amongst individuals, thereby influencing any given individual's capacity to respond to stressful environments such as low protein diet. Related effects were also found in response to a high-fat diet. I hypothesize that similar effects occur in humans. That is, an individual's inherent capacity to respond to conditions of stress is influenced by the genetic make up of their rDNA. I would like to identify such human rDNA variants and understand how they function. The proposed work has the potential to yield new and important insights into how gene-environment interactions influence phenotypic and disease outcomes in humans.