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Natural selection and molecular evolution in primate PAX9 gene, 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 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.

SUBMITTER: Pereira TV

PROVIDER: S-EPMC1458632 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature

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

Pereira Tiago V TV 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

Proceedings of the National Academy of Sciences of the United States of America 20060403 15

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 a ...[more]

PMID: 16585527

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Project description:Fusarium graminearum virus 1 (FgV1) is a positive-sense ssRNA virus that confers hypovirulence in its fungal host, Fusarium graminearum. Like most mycoviruses, FgV1 exists in fungal cells, lacks an extracellular life cycle, and is therefore transmitted during sporulation or hyphal anastomosis. To understand FgV1 evolution and/or adaptation, we conducted mutation accumulation (MA) experiments by serial passage of FgV1 alone or with FgV2, 3, or 4 in F. graminearum. We expected that the effects of positive selection would be highly limited because of repeated bottleneck events. To determine whether selection on the virus was positive, negative, or neutral, we assessed both the phenotypic traits of the host fungus and the RNA sequences of FgV1. We inferred that there was positive selection on beneficial mutations in FgV1 based on the ratio of non-synonymous to synonymous substitutions (d N /d S ), on the ratio of radical to conservation amino acid replacements (p NR /p NC ), and by changes in the predicted protein structures. In support of this inference, we found evidence of positive selection only in the open reading frame 4 (ORF4) protein of DK21/FgV1 (MA line 1); mutations at amino acids 163A and 289H in the ORF4 of MA line 1 affected the entire structure of the protein predicted to be under positive selection. We also found, however, that deleterious mutations were a major driving force in viral evolution during serial passages. Linear relationships between changes in viral fitness and the number of mutations in each MA line demonstrated that some deleterious mutations resulted in fitness decline. Several mutations in MA line 1 were not shared with any of the other four MA lines (PH-1/FgV1, PH-1/FgV1 + 2, PH-1/FgV1 + 3, and PH-1/FgV1 + 4). This suggests that evolutionary pathways of the virus could differ with respect to hosts and also with respect to co-infecting viruses. The data also suggested that the differences among MA lines might also be explained by mutational robustness and other unidentified factors. Additional research is needed to clarify the effects of virus co-infection on the adaptation or evolution of FgV1 to its environments.

Project description:BackgroundWe have examined the evolution of the genes at the major human beta-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus.ResultsWe provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on beta-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific beta-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of beta-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region.ConclusionsIdentification of these putatively functional sites has important implications for our understanding of beta-defensin function and for novel antibiotic design.

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

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

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