Why zebra finches don’t get hypercholesterolemia

Abstract

In his 1994 classic, "Why Zebras Don't Get Ulcers"(1), Robert Sapolsky chronicles how the pathological effects of chronic stress commonly seen in humans are much rarer in non-human animals. A new paper by Velho et al. (2) in this issue of Proceedings of the National Academy of Sciences reports a fascinating discovery that provides an update to this theme. In this paper, the authors investigate the evolution of a receptor involved in cholesterol uptake by cells that is also exploited by the vesicular stomatitis virus (VSV) to enter cells during infection. They find that in songbirds-including the popular lab model, the zebra finch-this low-density lipid receptor (LDLR) is missing several key protein coding regions that are found in many other avian groups as well as in mammals. This apparent case of evolutionary loss of function raises interesting questions about how songbirds manage to balance their cholesterol levels and avoid hypercholesterolemia (hence the title of this commentary). It also has important implications for a variety of other fields, ranging from efforts to use VSV-G pseudotyped lentiviruses as a tool to manipulate gene expression, to efforts to understand and control vesicular stomatitis, a major agricultural disease caused by VSV.