cis-Regulatory Changes in Kit Ligand Expression and Parallel Evolution of Pigmentation in Sticklebacks and Humans

HHMI and Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell (Impact Factor: 32.24). 01/2008; 131(6):1179-89. DOI: 10.1016/j.cell.2007.10.055
Source: PubMed


Dramatic pigmentation changes have evolved within most vertebrate groups, including fish and humans. Here we use genetic crosses in sticklebacks to investigate the parallel origin of pigmentation changes in natural populations. High-resolution mapping and expression experiments show that light gills and light ventrums map to a divergent regulatory allele of the Kit ligand (Kitlg) gene. The divergent allele reduces expression in gill and skin tissue and is shared by multiple derived freshwater populations with reduced pigmentation. In humans, Europeans and East Asians also share derived alleles at the KITLG locus. Strong signatures of selection map to regulatory regions surrounding the gene, and admixture mapping shows that the KITLG genomic region has a significant effect on human skin color. These experiments suggest that regulatory changes in Kitlg contribute to natural variation in vertebrate pigmentation, and that similar genetic mechanisms may underlie rapid evolutionary change in fish and humans.

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    • "A Human-Specific Deletion of a Hindlimb Enhancer in the GDF6 Locus Our combined mapping, expression, and transgenic experiments together provide strong evidence that cis-regulatory evolution of the GDF6 gene contributes to a classic skeletal difference in sticklebacks. Previous studies have shown that the same loci that underlie repeated evolution of stickleback traits may also be reused when related traits evolve in other species, including humans (Shapiro et al., 2006; Miller et al., 2007; Guenther et al., 2014). Because GDF6 shares the structural and developmental properties of other loci that appear to be favorable substrates for repeated evolution (Knecht et al., 2007; Stern and Orgogozo, 2009), we examined whether lineage-specific regulatory changes may have also occurred in GDF6 during evolution of novel skeletal structures in primates. "
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    • "Freshwater populations of stickleback have often evolved in parallel phenotypically (Cresko et al., 2007) and genetically (Hohenlohe et al., 2010a; Jones et al., 2012). Examination of these populations has allowed researchers to gain insight into the natural genetic variation that affects conserved complex biological processes such as craniofacial and dermal bone Disease Models & Mechanisms • DMM • Advance article development (Kimmel et al., 2005), pigmentation (Jones et al., 2012; Miller et al., 2007), and behavioral phenotypes (Wark et al., 2011), among other complex traits (Albert et al., 2008; McGuigan et al., 2011). "
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