The medaka mutation tintachina sheds light on the evolution of V-ATPase B subunits in vertebrates.
Vacuolar-type H(+) ATPases (V-ATPases) are multimeric protein complexes that play a universal role in the acidification of intracellular compartments in eukaryotic cells. We have isolated the recessive medaka mutation tintachina (tch), which carries an inactivating modification of the conserved glycine residue (G75R) of the proton pump subunit atp6v1Ba/vatB1. Mutant embryos show penetrant pigmentation defects, massive brain apoptosis and lethality before hatching. Strikingly, an equivalent mutation in atp6v1B1 (G78R) has been reported in a family of patients suffering from distal renal tubular acidosis (dRTA), a hereditary disease that causes metabolic acidosis due to impaired kidney function. This poses the question as to how molecularly identical mutations result in markedly different phenotypes in two vertebrate species. Our work offers an explanation for this phenomenon. We propose that, after successive rounds of whole-genome duplication, the emergence of paralogous copies allowed the divergence of the atp6v1B cis-regulatory control in different vertebrate groups.
1] Centre for Organismal Studies, COS, University of Heidelberg, Heidelberg, Germany [2].
Claudia
C
Müller
Ignacio
I
Maeso
Joachim
J
Wittbrodt
Juan R
JR
Martínez-Morales
D000818:Animals; D005075:Biological Evolution; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009990:Oryzias / Q000235:genetics*; D010641:Phenotype; D021122:Protein Subunits / Q000235:genetics*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics*
D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases