Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development.
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 approximately 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.
Pereira
Tiago V
TV
Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501-970 Porto Alegre, Brazil.
Salzano
Francisco M
FM
Mostowska
Adrianna
A
Trzeciak
Wieslaw H
WH
Ruiz-Linares
Andrés
A
Chies
José A B
JA
Saavedra
Carmen
C
Nagamachi
Cleusa
C
Hurtado
Ana M
AM
Hill
Kim
K
Castro-de-Guerra
Dinorah
D
Silva-Júnior
Wilson A
WA
Bortolini
Maria-Cátira
MC
D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D017124:Conserved Sequence; D003817:Dentition; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D051764:PAX9 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D011323:Primates / Q000235:genetics*; D017433:Protein Structure, Secondary; D012641:Selection, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014070:Tooth / Q000254:growth & development*; D014714:Vertebrates
D051764:PAX9 Transcription Factor