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, 19 (1), 31

Odontogenic Ameloblast-Associated (ODAM) Is Inactivated in Toothless/Enamelless Placental Mammals and Toothed Whales

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Odontogenic Ameloblast-Associated (ODAM) Is Inactivated in Toothless/Enamelless Placental Mammals and Toothed Whales

Mark S Springer et al. BMC Evol Biol.

Abstract

Background: The gene for odontogenic ameloblast-associated (ODAM) is a member of the secretory calcium-binding phosphoprotein gene family. ODAM is primarily expressed in dental tissues including the enamel organ and the junctional epithelium, and may also have pleiotropic functions that are unrelated to teeth. Here, we leverage the power of natural selection to test competing hypotheses that ODAM is tooth-specific versus pleiotropic. Specifically, we compiled and screened complete protein-coding sequences, plus sequences for flanking intronic regions, for ODAM in 165 placental mammals to determine if this gene contains inactivating mutations in lineages that either lack teeth (baleen whales, pangolins, anteaters) or lack enamel on their teeth (aardvarks, sloths, armadillos), as would be expected if the only essential functions of ODAM are related to tooth development and the adhesion of the gingival junctional epithelium to the enamel tooth surface.

Results: We discovered inactivating mutations in all species of placental mammals that either lack teeth or lack enamel on their teeth. A surprising result is that ODAM is also inactivated in a few additional lineages including all toothed whales that were examined. We hypothesize that ODAM inactivation is related to the simplified outer enamel surface of toothed whales. An alternate hypothesis is that ODAM inactivation in toothed whales may be related to altered antimicrobial functions of the junctional epithelium in aquatic habitats. Selection analyses on ODAM sequences revealed that the composite dN/dS value for pseudogenic branches is close to 1.0 as expected for a neutrally evolving pseudogene. DN/dS values on transitional branches were used to estimate ODAM inactivation times. In the case of pangolins, ODAM was inactivated ~ 65 million years ago, which is older than the oldest pangolin fossil (Eomanis, 47 Ma) and suggests an even more ancient loss or simplification of teeth in this lineage.

Conclusion: Our results validate the hypothesis that the only essential functions of ODAM that are maintained by natural selection are related to tooth development and/or the maintenance of a healthy junctional epithelium that attaches to the enamel surface of teeth.

Keywords: Edentulism; Enamel; Junctional epithelium; ODAM; Pseudogene.

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The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Maximum likelihood phylogram (ln L = − 27,926.663886) based on ODAM protein-coding sequences for 165 placental mammal species. Pink boxes indicate taxa with inactivating mutations in ODAM; green boxes indicate proboscideans that are missing exon 6 of ODAM. The tree is rooted between Atlantogenata and Boreoeutheria. Some clades for which all of the constituent taxa have intact ODAM sequences were collapsed, and the length of the Glires clade branch was halved to improve aesthetics (see TreeBASE [http://purl.org/phylo/treebase/phylows/study/TB2:S23531] for ML phylogram with all 165 taxa)
Fig. 2
Fig. 2
Examples of inactivating mutations in ODAM. a) Orycteropus afer (aardvark). b) Xenarthra (anteaters, sloths, armadillos). c) Manis spp. (pangolins). d) Cetacea (whales, dolphins, porpoises). Green boxes denote frameshift insertions; blue boxes denote frameshift deletions; and purple boxes denote premature stop codons. Loxodonta, Procavia, Hyaena, Canis, and Hippopotamus have intact ODAM sequences and were included in different alignment panels to provide context for inactivating mutations
Fig. 3
Fig. 3
Map to reference coverage of Illumina reads onto a contiguous block of Loxodonta africana (African savannah elephant) ODAM that begins with intron 5 and ends with exon 10. Map to reference results suggest that exon 6 is retained in Elephas maximus (Asian elephant) but is missing in several other proboscideans (Loxodonta cyclotis [African forest elephant], Mammuthus primigenius [woolly mammoth], Palaeoloxodon antiquus [straight-tusked elephant], Mammut americanum [American mastodon])
Fig. 4
Fig. 4
Bayesian reconstruction of dN/dS for 165 ODAM sequences across the placental phylogeny. The variation of dN/dS was jointly reconstructed with divergence times while controlling the effect of three life-history traits (body mass, longevity, and maturity). Asterisks at the tips of terminal branches indicate non-functional sequences (pseudogenes). Stars indicate branches on which shared inactivating mutations were inferred in toothless or enamelless clades. The tree is rooted between Atlantogenata and Boreoeutheria. Placental orders are delimited to the right of species tree tips
Fig. 5
Fig. 5
Estimated inactivation times in ENAM versus ODAM. a) Manis spp. (pangolins). b) Orycteropus afer (aardvark). c) Pilosa (anteaters, sloths) and Dasypus novemcinctus (nine-banded armadillo). Inactivation dates are mean values based on eight different combinations of two different codon models in codeml (CF1, CF2), fixed (1.0) versus estimated values for the dN/dS value on fully pseudogenic branches, and equations that permit for one versus two synonymous substitution rates [23]. Manis tricuspis is missing from the ODAM data set and M. javanica was not included in Meredith et al.’s [23] ENAM data set
Fig. 6
Fig. 6
Different hypotheses for the loss of ODAM exon 6 in some but not all proboscideans. a) Loss of ODAM exon 6 based on an ancestral polymorphism in the ancestor of Elephantidae and Mammutidae followed by incomplete lineage sorting of the two allelic variants in Recent and extinct proboscideans. b) One possible scenario for the loss of exon 6 of ODAM based on convergent loss in Mammut americanum and Palaeoloxodon antiquus followed by introgression of the sans exon 6 allele from P. antiquus to Loxodonta cyclotis and Mammuthus primigenius. Other scenarios are also possible based on directions of introgression within Elephantidae that were identified by Palkopoulou et al. [71]

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References

    1. Kawasaki K, Buchanan AV, Weiss KM. Biomineralization in humans: making the hard choices in life. Annu Rev Genet. 2009;43:119–142. doi: 10.1146/annurev-genet-102108-134242. - DOI - PubMed
    1. Kawasaki K. The SCPP gene family and the complexity of hard tissues in vertebrates. Cells Tissues Organs. 2011;194:108–112. doi: 10.1159/000324225. - DOI - PubMed
    1. Kawasaki K, Weiss KM. Mineralized tissue and vertebrate evolution: the secretory. Proc Natl Acad Sci USA. 2003;100:4060–4065. doi: 10.1073/pnas.0638023100. - DOI - PMC - PubMed
    1. Sire J-Y, Davit-Béal T, Delgado S, Gu X. The origin and evolution of enamel mineralization genes. Cells Tissues Organs. 2007;186:25–48. doi: 10.1159/000102679. - DOI - PubMed
    1. Bosshardt DD, Lang NP. The junctional epithelium: from health to disease. J Dent Res. 2005;84:9–20. doi: 10.1177/154405910508400102. - DOI - PubMed

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