Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Department of Cardio-Renal Physiopathology, National Institute of Cardiology Ignacio Chávez, Mexico City, Mexico.
Obesity (Silver Spring). 2022 Oct;30(10):1917-1926. doi: 10.1002/oby.23540.
Sixty years ago, the geneticist James Neel proposed that the epidemics of obesity and diabetes today may have evolutionary roots. Specifically, he suggested that our ancestors may have accumulated mutations during periods of famine that provided a survival advantage at that time. However, the presence of this "thrifty genotype" in today's world, where food is plentiful, would predispose us to obesity and diabetes. The "thrifty gene" hypothesis, attractive to some, has been challenged over the years. The authors have previously postulated that the loss of the uricase gene, resulting in a rise in serum and intracellular uric acid levels, satisfies the criteria of a thrifty genotype mutation. This paper reviews and brings up-to-date the evidence supporting the hypothesis and discusses the current arguments that challenge this hypothesis. Although further studies are needed to test the hypothesis, the evidence supporting a loss of uricase as a thrifty gene is substantial and supports a role for evolutionary biology in the pathogenesis of the current obesity and diabetes epidemics.
六十年前，遗传学家詹姆斯·尼尔（James Neel）提出，当今肥胖症和糖尿病的流行可能具有进化根源。具体而言，他认为，我们的祖先在饥荒时期可能积累了一些突变，这些突变在当时提供了生存优势。然而，在当今食物充足的世界中，这种“节俭基因型”会使我们容易肥胖和患上糖尿病。这个“节俭基因”假说对一些人来说很有吸引力，但多年来一直受到质疑。作者之前假设，尿酸酶基因的丧失导致血清和细胞内尿酸水平升高，符合节俭基因型突变的标准。本文回顾并更新了支持该假说的证据，并讨论了目前对该假说的挑战。尽管还需要进一步的研究来检验该假说，但支持尿酸酶缺失作为节俭基因的证据是充分的，这支持了进化生物学在当前肥胖和糖尿病流行的发病机制中的作用。
