title: RUNX2 tandem repeats and the evolution of facial length in placental mammals.
abstract: BACKGROUND
  When simple sequence repeats are integrated into functional genes, they can potentially act as evolutionary 'tuning knobs', supplying abundant genetic variation with minimal risk of pleiotropic deleterious effects. The genetic basis of variation in facial shape and length represents a possible example of this phenomenon. Runt-related transcription factor 2 (RUNX2), which is involved in osteoblast differentiation, contains a functionally-important tandem repeat of glutamine and alanine amino acids. The ratio of glutamines to alanines (the QA ratio) in this protein seemingly influences the regulation of bone development. Notably, in domestic breeds of dog, and in carnivorans in general, the ratio of glutamines to alanines is strongly correlated with facial length.
  
  
  RESULTS
  In this study we examine whether this correlation holds true across placental mammals, particularly those mammals for which facial length is highly variable and related to adaptive behavior and lifestyle (e.g., primates, afrotherians, xenarthrans). We obtained relative facial length measurements and RUNX2 sequences for 41 mammalian species representing 12 orders. Using both a phylogenetic generalized least squares model and a recently-developed Bayesian comparative method, we tested for a correlation between genetic and morphometric data while controlling for phylogeny, evolutionary rates, and divergence times. Non-carnivoran taxa generally had substantially lower glutamine-alanine ratios than carnivorans (primates and xenarthrans with means of 1.34 and 1.25, respectively, compared to a mean of 3.1 for carnivorans), and we found no correlation between RUNX2 sequence and face length across placental mammals.
  
  
  CONCLUSIONS
  Results of our diverse comparative phylogenetic analyses indicate that QA ratio does not consistently correlate with face length across the 41 mammalian taxa considered. Thus, although RUNX2 might function as a 'tuning knob' modifying face length in carnivorans, this relationship is not conserved across mammals in general.
authors: Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK.
authors: Marie A
authors: MA
authors: Pointer
authors: Jason M
authors: JM
authors: Kamilar
authors: Vera
authors: V
authors: Warmuth
authors: Stephen G B
authors: SG
authors: Chester
authors: Frédéric
authors: F
authors: Delsuc
authors: Nicholas I
authors: NI
authors: Mundy
authors: Robert J
authors: RJ
authors: Asher
authors: Brenda J
authors: BJ
authors: Bradley
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D005075:Biological Evolution; D002335:Carnivora / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D005145:Face / Q000033:anatomy & histology*; D008322:Mammals / Q000235:genetics*; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit