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Abstract:
Numerous loci of large effect have been shown to underlie phenotypic variation
between species. However, loci with subtle effects are presumably more frequently involved in
microevolutionary processes but have rarely been discovered. We explore the genetic basis of
shape variation in the first upper molar of hybrid mice between Mus musculus musculus and M. m.
domesticus. We performed the first genome-wide association study for molar shape and used 3D
surface morphometrics to quantify subtle variation between individuals. We show that many loci of
small effect underlie phenotypic variation, and identify five genomic regions associated with tooth
shape; one region contained the gene microphthalmia-associated transcription factor Mitf that has
previously been associated with tooth malformations. Using a panel of five mutant laboratory
strains, we show the effect of the Mitf gene on tooth shape. This is the first report of a gene
causing subtle but consistent variation in tooth shape resembling variation in nature.
