1. ¹Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, USA
2. ²Biology Department, Williams College, Williamstown, MA, USA
3. ³Eijkman Institute for Molecular Biology, Jakarta, Indonesia

Correspondence: Professor JA Wilder, Department of Biological Sciences, Northern Arizona University, South Beaver Street, PO Box 5640, Flagstaff, AZ 86011-5640, USA. E-mail: Jason.Wilder@nau.edu

Received 24 November 2008; Revised 5 January 2009; Accepted 8 January 2009; Published online 20 February 2009.

Abstract

Southeast Asian ovalocytosis (SAO) is an erythrocyte abnormality that protects affected individuals from cerebral malaria. This trait is caused by a 27-bp deletion in the SLC4A1 gene, which is lethal when homozygous. We reseqeunced approximately 5 kb of SLC4A1 in an Indonesian population where SAO is prevalent to better understand the evolution of this clinically important trait. The four SAO chromosomes we resequenced share a single haplotype that differs from a sampled non-SAO haplotype only by the 27-bp deletion. Comparison of Indonesian sequence data to that from two other Asian populations (aboriginal Taiwanese and Japanese) shows Indonesian SLC4A1 to be strongly differentiated from the Taiwanese, but not the Japanese. Indeed, the Taiwanese sample contains only chromosomes that are highly divergent from all sampled SAO chromosomes. Because earlier studies have found an association between Austronesian-speakers (who most likely originated in Taiwan) and SAO, our failure to find SAO-like chromosomes in Taiwan is unexpected. Finally, our data find a strong excess of high-frequency derived alleles in all three populations. These alleles include the non-synonymous 'Memphis' variant, which is known to affect anion transport across the erythrocyte membrane. Our data suggest a role for recent natural selection acting on Memphis or a linked variant.