A new study, published in Nature Communications, found that two seemingly unrelated genes (Nprl3 and alpha-globin) that have been neighbours for over 500 million years, share enhancers for joint control of metabolism and red blood cell development (known as erythropoiesis). This provides a functional explanation for the deep-time co-conservation of these genes, and advances understanding of the complex process by which red blood cells develop from their precursor cells to carry out their essential oxygen-carrying role.
In erythropoiesis, precursor cells undergo changes in metabolism and gene expression to degrade organelles and favour production of the oxygen-carrying protein haemoglobin. Preston et al approached erythropoiesis from a metabolic perspective, and used transgenic animal models developed over several years by the Higgs Group to study alpha-globin (a sub-unit of haemoglobin).
Expression of alpha-globin is highly upregulated during erythropoiesis. Most of the enhancers responsible for this are found within a neighbouring gene called Nprl3, which serves a key role in cell metabolism. The Nprl3 and alpha-globin genes have been genomically adjacent for over half a billion years (back to jawless vertebrates).
Read the full story on the MRC Weatherall Institute of Molecular Medicine (WIMM) website.