Natural selection and molecular evolution in primatePAX9gene, a major determinant of tooth development

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 Ϸ2.1 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. human evolution ͉ tooth agenesis ͉ evolutionary window

Association of common PAX9 variants with permanent tooth size variation in non-syndromic East Asian populations

“…Other studies have also failed to show any association between PAX9 SNPs and sporadic tooth agenesis in the Polish and Chinese subjects. 35,36 If we assume the previously observed value (1.75) of the odds ratio, the estimated power for the sample size of our test is calculated to be 76%. As the sample sizes were relatively small in both the previous and present studies, statistical error may explain the aforementioned difference in outcomes between the studies.…”

“…46,47 One of the SNPs that showed significant association with crown size in our study, rs4904210, is a non-synonymous SNP located in a region of exon 4 that is highly conserved among mammals. 35 In addition, it has been predicted using computer programs that the Ala-to-Pro amino-acid change affects the protein structure. 35 However, these pieces of indirect evidence cannot be an adequate explanation for the functional change of the PAX9 protein.…”

“…35 In addition, it has been predicted using computer programs that the Ala-to-Pro amino-acid change affects the protein structure. 35 However, these pieces of indirect evidence cannot be an adequate explanation for the functional change of the PAX9 protein. As the LD block that includes the examined SNPs ranges widely, it would be difficult without functional assays to determine which SNP is responsible.…”

Relation between agenesis and shape anomaly of maxillary lateral incisors and canine impaction

“…Besides tooth size reduction and impacted canine, other dental anomalies in this complex genetic tracing as hypodontia, infraocclusion, late eruption, ectopic eruption of permanent first molars and certain canine transpositions share some common genetic control. 15,16,18,28,29 Thus, the appearance of small permanent incisors in the initial mixed dentition, especially combined with some of the other associated dental anomalies, could be a useful indicator of future occurrence of impacted canines. 15,16,18,25,29,32,36 It was concluded in this work that every patient that presents agenesis or shape anomaly of maxillary lateral incisor must be analyzed in advance through specific examination, for they demonstrate strong tendency to present impacted upper canines.…”

PAX9 Mutation of Non-Syndromic Hypodontia in a Malaysian Family

“…Then, genomic DNA will be extracted from saliva using the QIAamp sample DNA MiniKit (Qiagen). PAX9 exons 2 (640 bp) and exon 3 (589 bp) were amplified using primers and conditions described in Pereira et al 9 PCR products were purified using Gel/PCR DNA fragment extraction kit (Geneaid). Both DNA strands were sent for sequencing.…”