Article

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: 33.12). 01/2008; 131(6):1179-89. DOI: 10.1016/j.cell.2007.10.055
Source: PubMed

ABSTRACT 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.

Full-text

Available from: Dolph Schluter, Apr 19, 2015
1 Follower
 · 
147 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Armor plate changes in sticklebacks are a classic example of repeated adaptive evolution. Previous studies identified ectodysplasin (EDA) gene as the major locus controlling recurrent plate loss in freshwater fish, though the causative DNA alterations were not known. Here we show that freshwater EDA alleles have cis-acting regulatory changes that reduce expression in developing plates and spines. An identical T->G base pair change is found in EDA enhancers of divergent low-plated fish. Recreation of the T->G change in a marine enhancer strongly reduces expression in posterior armor plates. Bead implantation and cell culture experiments show that Wnt signaling strongly activates the marine EDA enhancer, and the freshwater T->G change reduces Wnt responsiveness. Thus parallel evolution of low-plated sticklebacks has occurred through a shared DNA regulatory change, which reduces the sensitivity of an EDA enhancer to Wnt signaling, and alters expression in developing armor plates while preserving expression in other tissues.
    eLife Sciences 01/2015; 4. DOI:10.7554/eLife.05290 · 8.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Retinoic acid (RA) signaling exerts several important functions during vertebrate development. Several cell types derived from neural crest cells (NCC) have been shown to require balanced RA levels for their development. The neural crest is a transient, multipotent embryonic tissue, which also gives rise to melanophores and other pigment cell types. Here, I examined whether RA signaling is involved in NCC-derived melanophore development. My results indicate that enhanced RA levels cause hyperpigmentation in zebrafish larvae by increasing the melanoblast population, most likely by interfering with NCC development. I suggest that RA acts on NCCs, through either enhancing NCC induction, promoting proliferation, or inhibiting NCC apoptosis. It remains to be shown whether RA exerts additional functions within the melanophore lineage or, if the observations are primarily caused by RA´s well known function within NCC development.
    02/2015, Supervisor: Nicola Blum, Gerrit Begemann
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The analysis of genetic and epigenetic mechanisms of the genotype-phenotypic connection has, so far, only been possible in a handful of genetic model systems. Recent technological advances, including next-generation sequencing methods such as RNA-seq, ChIP-seq and RAD-seq, and genome-editing approaches including CRISPR-Cas, now permit to address these fundamental questions of biology also in organisms that have been studied in their natural habitats. We provide an overview of the benefits and drawbacks of these novel techniques and experimental approaches that can now be applied to ecological and evolutionary vertebrate models such as sticklebacks and cichlid fish. We can anticipate that these new methods will increase the understanding of the genetic and epigenetic factors influencing adaptations and phenotypic variation in ecological settings. These new arrows in the methodological quiver of ecologist will drastically increase the understanding of the genetic basis of adaptive traits - leading to a further closing of the genotype-phenotype gap.
    BioEssays 02/2015; 37(2):213-226. DOI:10.1002/bies.201400142 · 4.84 Impact Factor