The question of ethnic variability and the Darwinian significance of physiological neonatal jaundice in East Asian populations Daniel E. Wasser a, * , Israel Hershkovitz b a Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel b Anatomy and Anthropology Department, Tel Aviv University, Ramat Aviv 69978, Israel article info Article history: Received 27 January 2010 Accepted 16 February 2010 summary Recent work in Darwinian medicine has suggested that physiological neonatal jaundice (PNJ) might serve an adaptive function in scavenging reactive oxygen species that in later life are removed by the mature antioxidant enzyme system in the liver. This treatise examines this hypothesis in light of novel epidemi- ological and genetic findings which suggest that the incidence of PNJ is significantly increased in East Asian populations. Though found across all ethnic groups, it has been established that neonates of East Asian origin are at a significantly greater risk of developing PNJ, with more than one studying finding the incidence to be near double. For any Darwinian explanation of physiological neonatal jaundice to be considered in clinical circles, it is essential that the elevated incidence of PNJ in this population be explained both mechanistically and in terms of adaptation. Recent work has linked PNJ to a specific enzyme polymorphism, a variation of the UGT1A1 gene, in the glucoronidation pathway which is essen- tial for bilirubin metabolism and is strongly correlated with ethnic origin. In this paper it is hypothesized that the elevated incidence of PNJ in East Asian populations is not random or due to a flaw in the system but rather due to an evolved mechanism. Two potential pressures which might have selected for an ele- vated neonatal bilirubin in East Asian populations versus other ethnic groups are a diminished ability to reduce harmful oxidant radicals due to variations the P450 liver metabolic pathway and the endemic nat- ure of Hepatitis B in the Asia–Pacific region. This is the first work to attempt to explain PNJ through a Dar- winian yet clinically relevant lens while suggesting a specific proximate mechanism that is correlated with a pre-existing evolutionary environment and can be associated with differential reproductive success. Ó 2010 Elsevier Ltd. All rights reserved. Introduction Since first suggested that physiological hyperbilirubinemia in newborn infants might have an adaptive function [1], the claim has been generally accepted both by Darwinian medicine propo- nents [2–4] and the clinical community [5,6]. The basic argument is that the significantly increased level of bilirubin seen in other- wise healthy neonates during the first few weeks of life should not be understood as a problem or disease but as an adaptive pro- cess, namely scavenging reactive oxygen species that in later life are removed by the mature antioxidant enzyme system in the liver [5]. Furthermore, it has been suggested that this mechanism is un- der genetic control and subject to selective pressure [7]. However, these initial arguments are theoretical and require further verifica- tion. Recent epidemiological work has found that the incidence of physiological neonatal jaundice (PNJ) varies significantly between ethnic groups with a dramatic preponderance in individuals of East Asian ancestry [8–10], which excludes the possibility that PNJ is merely the evolutionary tradeoff humans pay for developing a lar- ger brain which limits the potential length of pregnancy to allow effective delivery. This prospectus combines recent work on genet- ic polymorphisms in East Asian liver metabolism, particularly the cytochrome p450 system [11,12], with the above mentioned find- ings of ethnic variability to suggest that the dramatic differences in the incidence of PNJ can be understood as an evolved mechanism which allows individuals to cope with variant liver metabolic pro- files due to altered enzymatic function. What is physiological neonatal jaundice? Physiological neonatal jaundice is the most common condition requiring medical attention in the full term newborn. It is a high- risk condition that presents with a sudden rapid rise in serum bil- irubin values. The accumulation of unconjugated bilirubin results in a yellow coloration of the skin and sclera in newborns with jaun- dice [6]. Although for most neonates the condition passes without needing therapy, in some cases medical intervention in the form of phototherapy is required as unconjugated bilirubin is neurotoxic 0306-9877/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2010.02.017 * Corresponding author. Tel.: +972 1 805 617 4017. E-mail addresses: danwasser86@gmail.com (D.E. Wasser), anatom2@post.tau. ac.il (I. Hershkovitz). Medical Hypotheses 75 (2010) 187–189 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy