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Deletion/loss of bone morphogenetic protein 7 changes tooth morphology and function in Mus musculus: implications for dental evolution in mammals.

ABSTRACT: Quantifying regulatory gene effects on dental morphology and function has implications for the underlying mechanisms that generated dental diversity in mammals. We tested the hypothesis that regulatory gene expression changes lead to differences in molars using a neural crest knockout of bone morphogenetic protein 7 (BMP7) in Mus musculus. Three-dimensional geometric morphometric methods were used to quantify the shape of the molar toothrow. BMP7 mutants have extra cusps on the first upper and lower molars, and alterations in cusp orientation and morphology. Furthermore, significant shape differences between control and mutant were found for upper and lower toothrows. Mutant mice also exhibited differences in attrition facets, indicating functional changes that could lead to advantages in chewing new food resources and eventually niche diversification. The size ratio of the molars in the toothrow remained unchanged, implying that BMP7-induced changes in molar size ratio are a result of knocking out epithelial, rather than neural crest, expression of BMP7. Our results indicate that changes in BMP7 expression are sufficient to alter the morphology and function of the toothrow, suggesting that BMP7 or genes affecting its function could have played a role in structuring the dental diversity of extinct and extant mammals.

SUBMITTER: Zurowski C

PROVIDER: S-EPMC5792877 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Deletion/loss of bone morphogenetic protein 7 changes tooth morphology and function in <i>Mus musculus:</i> implications for dental evolution in mammals.

Zurowski Chelsey C Jamniczky Heather H Graf Daniel D Theodor Jessica J

Royal Society open science 20180103 1

Quantifying regulatory gene effects on dental morphology and function has implications for the underlying mechanisms that generated dental diversity in mammals. We tested the hypothesis that regulatory gene expression changes lead to differences in molars using a neural crest knockout of bone morphogenetic protein 7 (BMP7) in <i>Mus musculus</i>. Three-dimensional geometric morphometric methods were used to quantify the shape of the molar toothrow. BMP7 mutants have extra cusps on the first uppe ...[more]

PMID: 29410800

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Project description:BackgroundThe mammalian vomeronasal organ (VNO) expresses two G-protein coupled receptor gene families that mediate pheromone responses, the V1R and V2R receptor genes. In rodents, there are ~150 V1R genes comprising 12 subfamilies organized in gene clusters at multiple chromosomal locations. Previously, we showed that several of these subfamilies had been extensively modulated by gene duplications, deletions, and gene conversions around the time of the evolutionary split of the mouse and rat lineages, consistent with the hypothesis that V1R repertoires might be involved in reinforcing speciation events. Here, we generated genome sequence for one large cluster containing two V1R subfamilies in Mus spretus, a closely related and sympatric species to Mus musculus, and investigated evolutionary change in these repertoires along the two mouse lineages.ResultsWe describe a comparison of spretus and musculus with respect to genome organization and synteny, as well as V1R gene content and phylogeny, with reference to previous observations made between mouse and rat. Unlike the mouse-rat comparisons, synteny seems to be largely conserved between the two mouse species. Disruption of local synteny is generally associated with differences in repeat content, although these differences appear to arise more from deletion than new integrations. Even though unambiguous V1R orthology is evident, we observe dynamic modulation of the functional repertoires, with two of seven V1Rb and one of eleven V1Ra genes lost in spretus, two V1Ra genes becoming pseudogenes in musculus, two additional orthologous pairs apparently subject to strong adaptive selection, and another divergent orthologous pair that apparently was subjected to gene conversion.ConclusionTherefore, eight of the 18 (~44%) presumptive V1Ra/V1Rb genes in the musculus-spretus ancestor appear to have undergone functional modulation since these two species diverged. As compared to the rat-mouse split, where modulation is evident by independent expansions of these two V1R subfamilies, divergence between musculus and spretus has arisen more by mutations within coding sequences. These results support the hypothesis that adaptive changes in functional V1R repertoires contribute to the delineation of very closely related species.

Project description:BACKGROUND:Identification of protein-protein interactions is an important first step to understand living systems. High-throughput experimental approaches have accumulated large amount of information on protein-protein interactions in human and other model organisms. Such interaction information has been successfully transferred to other species, in which the experimental data are limited. However, the annotation transfer method could yield false positive interologs due to the lack of conservation of interactions when applied to phylogenetically distant organisms. RESULTS:To address this issue, we used phylogenetic profile method to filter false positives in interologs based on the notion that evolutionary conserved interactions show similar patterns of occurrence along the genomes. The approach was applied to Mus musculus, in which the experimentally identified interactions are limited. We first inferred the protein-protein interactions in Mus musculus by using two approaches: i) identifying mouse orthologs of interacting proteins (interologs) based on the experimental protein-protein interaction data from other organisms; and ii) analyzing frequency of mouse ortholog co-occurrence in predicted operons of bacteria. We then filtered possible false-positives in the predicted interactions using the phylogenetic profiles. We found that this filtering method significantly increased the frequency of interacting protein-pairs coexpressed in the same cells/tissues in gene expression omnibus (GEO) database as well as the frequency of interacting protein-pairs shared the similar Gene Ontology (GO) terms for biological processes and cellular localizations. The data supports the notion that phylogenetic profile helps to reduce the number of false positives in interologs. CONCLUSION:We have developed protein-protein interaction database in mouse, which contains 41109 interologs. We have also developed a web interface to facilitate the use of database http://lgsun.grc.nia.nih.gov/mppi/.

Dataset Information

Deletion/loss of bone morphogenetic protein 7 changes tooth morphology and function in Mus musculus: implications for dental evolution in mammals.

Publications

Deletion/loss of bone morphogenetic protein 7 changes tooth morphology and function in <i>Mus musculus:</i> implications for dental evolution in mammals.

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