SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans

• DOI: 10.1126/science.1116238
• Publication Date: 2005-12-15T22:02:46Z
• Authors: Rebecca L. Lamason; Manzoor-Ali P.K. ...; Jason R. Mest; Andrew C. Wong; Heather L. Norton; Michele C. Aros; Michael J. Jurynec; Xianyun Mao; Vanessa R. Humphr...; Jasper E. Humbert; Soniya Sinha; Jessica L. Moore; Pudur Jagadeeswaran; Wei Zhao; Gang Ning; Izabela Makalowska; Paul M. McKeigue; David O'Donnell; Rick Kittles; Esteban J. Parra; Nancy J. Mangini; David J. Grunwald; Mark D. Shriver; Victor A. Canfield; Keith C. Cheng
• Keywords: Melanins; 0301 basic medicine; Heterozygote; Alanine; Ion Transport; Melanosomes; Black People; Genetic Variation; Biological Evolution; Antiporters; Black or African American; Mice; 03 medical and health sciences; Asian People; Gene Frequency; Genes; Haplotypes; Animals; Humans; Calcium; Amino Acid Sequence; Alleles

Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved ancestral allele of a human coding polymorphism predominates in African and East Asian populations. In contrast, the variant allele is nearly fixed in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations, suggesting a key role for the SLC24A5 gene in human pigmentation.