SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans.
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.
Lamason
Rebecca L
RL
Jake Gittlen Cancer Research Foundation, Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Mohideen
Manzoor-Ali P K
MA
Mest
Jason R
JR
Wong
Andrew C
AC
Norton
Heather L
HL
Aros
Michele C
MC
Jurynec
Michael J
MJ
Mao
Xianyun
X
Humphreville
Vanessa R
VR
Humbert
Jasper E
JE
Sinha
Soniya
S
Moore
Jessica L
JL
Jagadeeswaran
Pudur
P
Zhao
Wei
W
Ning
Gang
G
Makalowska
Izabela
I
McKeigue
Paul M
PM
O'donnell
David
D
Kittles
Rick
R
Parra
Esteban J
EJ
Mangini
Nancy J
NJ
Grunwald
David J
DJ
Shriver
Mark D
MD
Canfield
Victor A
VA
Cheng
Keith C
KC
D001741:Black or African American / Q000235:genetics; D000409:Alanine / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D044466:Asian People / Q000235:genetics; D005075:Biological Evolution; D044383:Black People / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D005787:Gene Frequency; D005796:Genes; D014644:Genetic Variation; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D017136:Ion Transport; D008543:Melanins / Q000032:analysis; D020460:Melanosomes / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008969:Molecular Sequence Data; D020412:Multifactorial Inheritance; D009154:Mutation; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000648:ultrastructure; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D012880:Skin Pigmentation / Q000235:genetics*; D013912:Threonine / Q000235:genetics; D044465:White People / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
D017920:Antiporters; D008543:Melanins; C506584:SLC24A5 protein, human; C506583:SLC24A5 protein, zebrafish; D029961:Zebrafish Proteins; D013912:Threonine; D000409:Alanine; D002118:Calcium