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MBE Advance Access published online on December 2, 2005
Molecular Biology and Evolution, doi:10.1093/molbev/msj072
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© The Author 2005. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted November 28, 2005

Research Article

Molecular Evolution of the Primate Developmental Genes MSX1 and PAX9

George H. Perry 1, Brian C. Verrelli 2, and Anne C. Stone 1 *

1 School of Human Evolution and Social Change, Arizona State University
2 Center for Evolutionary Functional Genomics, The Biodesign Institute, and School of Life Sciences, Arizona State University

* To whom correspondence should be addressed.
Anne C. Stone, E-mail: acstone{at}asu.edu


  Abstract

In primates, the craniofacial skeleton and the dentition are marked by high levels of interspecific variation. Despite this, there are few comparative species studies conducted at the molecular level to investigate this functional diversity. We have determined nucleotide sequences of MSX1 and PAX9, two developmental genes, in a sample of 27 diverse primate species in order to identify coding or regulatory variation that may be associated with phenotypic diversity. Our analyses have identified four highly conserved noncoding sequences (CNS), including one that is conserved across primates and with dog, but not with mouse. Although we find that substitution rates vary significantly across MSX1 exons, comparisons of nonsynonymous and synonymous substitution rates (dN/dS) suggest that, as a whole, MSX1 and PAX9 amino acid sequences have been under functional constraint throughout primate evolution. Compared to all other primates in our sample, our analysis of exon 1 in MSX1 finds an unusual pattern of amino acid substitution for Tarsius syrichta, a member of a lineage (tarsiers) that has many unique features among primates. For example, tarsiers are the only extant primates without deciduous incisors, and MSX1 is expressed exclusively in the incisor regions during the earliest stages of dental development. Our overall results provide insight into the utility of comparative species analyses of highly conserved developmental genes and their roles in the evolution of complex phenotypes.

Keywords: comparative genomics; conserved noncoding sequence; homeobox; craniofacial skeleton; dentition; tarsier; callitrichid; strepsirrhine.
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H. Takahashi, A. Kamiya, A. Ishiguro, A. C. Suzuki, N. Saitou, A. Toyoda, and J. Aruga
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