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.
Highlights
Understanding the genetic basis of evolution requires the identification of genes and mutations responsible for phenotypic variation between individuals and populations
There have been many other studies exploring the genetic basis of shape variation, but given the highly polygenic nature of these traits it has been difficult to validate the extensive list of candidate genes identified through quantitative trait loci (QTL) and genome-wide association (GWAS) approaches
We focused on the first upper molar and used mice derived from a wild population, which allowed us to directly address the genetic basis of molar shape variation from a micro-evolutionary perspective
Summary
Understanding the genetic basis of evolution requires the identification of genes and mutations responsible for phenotypic variation between individuals and populations. There have been many other studies exploring the genetic basis of shape variation (e.g. craniofacial shape), but given the highly polygenic nature of these traits it has been difficult to validate the extensive list of candidate genes identified through quantitative trait loci (QTL) and genome-wide association (GWAS) approaches. The mouse tooth is one of the traits extensively studied regarding shape variation. In paleontology, it is a key character for phylogenetic and dietary inferences (Misonne, 1969; Gomez Cano et al, 2013). It is a key character for phylogenetic and dietary inferences (Misonne, 1969; Gomez Cano et al, 2013) It has been a model for developmental genetics (Jernvall and Thesleff, 2012; Urdy et al, 2016). The genes and pathways involved in tooth morphogenesis are well known
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