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

Tiago V. Pereira, Francisco M. Salzano, Adrianna Mostowska, Wieslaw H. Trzeciak, Andrés Ruiz-Linares, José A.B. Chies, Carmen Saavedra, Cleusa Nagamachi, Ana M. Hurtado, Kim Hill, Dinorah Castro-De-Guerra, Wilson A. Silva, Maria Cátira Bortolini

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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 oriholog 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.

Original languageEnglish (US)
Pages (from-to)5676-5681
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - Apr 11 2006
Externally publishedYes


  • Evolutionary window
  • Human evolution
  • Tooth agenesis

ASJC Scopus subject areas

  • General


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