Our research underscores that the whole genome needs to be considered in order to fully capture how genetic variation can contribute to health and disease.
Dr Michelle Holland, Lecturer in Epigenetics and Post-transcriptional Gene Regulation
18 July 2024
Ribosomal DNA copy number found to affect weight gain
New research has found that ribosomal DNA, a previously overlooked repetitive region of the genome could impact the ability to gain weight, highlighting the importance of such regions for human health.
Researchers have found that ribosomal DNA, a previously overlooked repetitive region of the genome, could impact the ability of people to gain weight. The results have identified a link between increased body mass and having less copies of the rDNA genes.
As body mass and weight gain is widely known to be caused by a vast array of genetic and environmental factors, understanding each of these factors has proven an incredibly complicated task for researchers.
The majority of the genome is composed of ‘repetitive regions’ - stretches of the same or similar nucleotide sequences. Ribosomal DNA (rDNA), an example of a repetitive region, produces essential components of ribosomes – the cellular machines that manufacture proteins. They are repetitive because each cell contains hundreds of copies to manage the demands of protein synthesis.
Previous studies have not considered these parts of the genome due to technical reasons. New research led by Dr Michelle Holland uses whole genome sequencing techniques to analyse the repetitive regions, including rDNA in rats and humans, and highlights the important role that repetitive regions play in human health.
Further analysis confirmed that this association was not due to other cellular changes that occur as BMI increases, such as increased number of inflammatory cells and the association between rDNA and weight gain was identified in both rats and multiple types of human tissue. Identical twins with different BMIs were also found to have the same number of rDNA copies, suggesting that the association is causal rather than consequential.
Though an association has been identified, there is no explanation of the cellular and chemical mechanisms that link rDNA copy number to control of body weight. The authors believe that is may result from effects on the developing embryo, where the rDNA is dynamically regulated by chemical mechanisms that act to fine tune the number of active copies that are active.
To better understand how ribosomal DNA controls body weight, Dr Michelle Holland’s group are currently planning to analyse UK Biobank data to determine the best direction for future investigations into the underlying mechanisms.
As one of the first examples to demonstrate that the number of rDNA genes can affect a human trait, these results highlight the importance of analysing traditionally overlooked repetitive regions of the genome to better understanding the genetic contribution to human health and traits.
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