Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development

doi:10.1073/pnas.0509562103

Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development

^†Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501-970 Porto Alegre, Brazil;
^§Department of Biochemistry and Molecular Biology, University of Medical Sciences, 6 Swiecickiego, 60-781, Poznan, Poland;
^¶The Galton Laboratory, University College London, 4 Stephenson Way, London NW1 2HE, United Kingdom;
^‖Departamento de Genética, Centro de Ciências Biológicas, Universidade Federal do Pará, Campus Universitário do Guamá, 66075-970 Belém, Brazil;
^††Department of Anthropology, University of New Mexico, Albuquerque, NM 87131;
^‡‡Laboratório de Genética Humana, Instituto Venezolano de Investigaciones Científicas, Apartado 21827, Caracas 1020A, Venezuela; and
^§§Departamento de Genética, Faculdade de Medicina, Universidade de São Paulo, Campus Universitário, 14049-900 Ribeirão Preto, Brazil

Contributed by Francisco M. Salzano, December 8, 2005

Abstract

Large differences in relation to dental size, number, and morphology among and within modern human populations and between modern humans and other primate species have been observed. Molecular studies have demonstrated that tooth development is under strict genetic control, but, the genetic basis of primate tooth variation remains unknown. The PAX9 gene, which codes for a paired domain-containing transcription factor that plays an essential role in the development of mammal dentition, has been associated with selective tooth agenesis in humans and mice, which mainly involves the posterior teeth. To determine whether this gene is polymorphic in humans, we sequenced ≈2.1 kb of the entire four-exon region (exons 1, 2, 3 and 4; 1,026 bp) and exon-intron (1.1 kb) boundaries of 86 individuals sampled from Asian, European, and Native American populations. We provided evidence that human PAX9 polymorphisms are limited to exon 3 only and furnished details about the distribution of a mutation there in 350 Polish subjects. To investigate the pattern of selective pressure on exon 3, we sequenced ortholog regions of this exon in four species of New World monkeys and one gorilla. In addition, orthologous sequences of PAX9 available in public databases were also analyzed. Although several differences were identified between humans and other species, our findings support the view that strong purifying selection is acting on PAX9. New World and Old World primate lineages may, however, have different degrees of restriction for changes in this DNA region.

Footnotes

^‡To whom correspondence should be addressed. E-mail: francisco.salzano{at}ufrgs.br
Author contributions: M.-C.B. designed research; T.V.P. performed research; A.M., W.H.T., C.N., A.M.H., and K.H. contributed samples for analysis; T.V.P., F.M.S., A.R.-L., J.A.B.C., C.S., D.C.-d.-G., W.A.S.-J., and M.-C.B. analyzed data; and T.V.P., F.M.S., and M.-C.B. wrote the paper.
Conflict of interest statement: No conflicts declared.
Data deposition: The DNA sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ250008–DQ250012).
Abbreviations:

Abbreviations:

NW,

New World;

dN,

nonsynonymous divergence;

dS,

synonymous divergence.