ArticlePDF Available

Molecular Decay of the Tooth Gene Enamelin (ENAM) Mirrors the Loss of Enamel in the Fossil Record of Placental Mammals

PLOS
PLOS Genetics
Authors:
Robert W Meredith at Montclair State University
Robert W Meredith
John Gatesy
John Gatesy
John Gatesy
  • This person is not on ResearchGate, or hasn't claimed this research yet.
William J Murphy at Texas A&M University
William J Murphy
Oliver A Ryder at San Diego Zoo
Oliver A Ryder
Show all 5 authorsHide
Download full-text PDFDownload full-text PDF
Read full-text
Download citation

Abstract and Figures

Author Summary Enamel is the hardest substance in the vertebrate body. One of the key proteins involved in enamel formation is enamelin. Most placental mammals have teeth that are capped with enamel, but there are also lineages without teeth (anteaters, pangolins, baleen whales) or with enamelless teeth (armadillos, sloths, aardvarks, pygmy and dwarf sperm whales). All toothless and enamelless mammals are descended from ancestral forms that possessed teeth with enamel. Given this ancestry, we predicted that mammalian species without teeth or with teeth that lack enamel would have copies of the gene that codes for the enamelin protein, but that the enamelin gene in these species would contain mutations that render it a nonfunctional pseudogene. To test this hypothesis, we sequenced most of the protein-coding region of the enamelin gene in all groups of placental mammals that lack teeth or have enamelless teeth. In every case, we discovered mutations in the enamelin gene that disrupt the proper reading frame that codes for the enamelin protein. Our results link evolutionary change at the molecular level to morphological change in the fossil record and also provide evidence for the enormous predictive power of Charles Darwin's theory of descent with modification.
Species tree with frameshift mutations and dN/dS branch coding. Symbols next to taxon names denote taxa having teeth with enamel, taxa having teeth without enamel, and edentulous taxa. Branches are functional (black), pre-mutation (blue), mixed (purple), and pseudogenic (red). Vertical bars on branches represent frameshift mutations (see Table S1). Frameshifts that map unambiguously onto branches are shown in black. Frameshifts shown in white are unique, but occur in regions where sequences are missing for one or more taxa (Figure S7) and were arbitrarily mapped onto the youngest possible branch. Homoplastic frameshifts (deltran optimization) are marked by numbers. Numbers after taxon names indicate the minimum number of stop codons in the sequence (before slashes) and the length of the sequence (after slashes). doi:10.1371/journal.pgen.1000634.g001
Species tree with frameshift mutations and dN/dS branch coding. Symbols next to taxon names denote taxa having teeth with enamel, taxa having teeth without enamel, and edentulous taxa. Branches are functional (black), pre-mutation (blue), mixed (purple), and pseudogenic (red). Vertical bars on branches represent frameshift mutations (see Table S1). Frameshifts that map unambiguously onto branches are shown in black. Frameshifts shown in white are unique, but occur in regions where sequences are missing for one or more taxa (Figure S7) and were arbitrarily mapped onto the youngest possible branch. Homoplastic frameshifts (deltran optimization) are marked by numbers. Numbers after taxon names indicate the minimum number of stop codons in the sequence (before slashes) and the length of the sequence (after slashes). doi:10.1371/journal.pgen.1000634.g001
… 
Examples of frameshift mutations and stop codons in edentulous and enamelless taxa. (A) Orycteropus. (B) Manis. (C) Cetacea. (D) Xenarthra. Frameshift insertions are highlighted in blue, frameshift deletions are highlighted in red, and stop codons are highlighted in green. Also see Figure S5.
Examples of frameshift mutations and stop codons in edentulous and enamelless taxa. (A) Orycteropus. (B) Manis. (C) Cetacea. (D) Xenarthra. Frameshift insertions are highlighted in blue, frameshift deletions are highlighted in red, and stop codons are highlighted in green. Also see Figure S5.
… 
Examples of frameshift mutations and stop codons in edentulous and enamelless taxa. (A) Orycteropus . (B) Manis . (C) Cetacea. (D) Xenarthra. Frameshift insertions are highlighted in blue, frameshift deletions are highlighted in red, and stop codons are highlighted in green. Also see Figure S5. doi:10.1371/journal.pgen.1000634.g002
Examples of frameshift mutations and stop codons in edentulous and enamelless taxa. (A) Orycteropus . (B) Manis . (C) Cetacea. (D) Xenarthra. Frameshift insertions are highlighted in blue, frameshift deletions are highlighted in red, and stop codons are highlighted in green. Also see Figure S5. doi:10.1371/journal.pgen.1000634.g002
… 
A synthetic interpretation of the history of enamel degeneration in Tubulidentata (aardvarks) based on fossils, phylogenetics, molecular clocks, frameshift mutations, and dN/dS ratios. Estimates for the timing of the transition from functional gene to pseudogene are based on decomposition of mixed dN/dS history into two distinct episodes of evolution under purifying selection and neutral evolution, respectively. The divergence time between Tubulidentata and Afrosoricida (golden moles, tenrecs) + Macroscelidea (elephant shrews) is from Murphy and Eizirik [23]. The age of the oldest aardvark, O. minutus , is from Milledge [25]. doi:10.1371/journal.pgen.1000634.g003
A synthetic interpretation of the history of enamel degeneration in Tubulidentata (aardvarks) based on fossils, phylogenetics, molecular clocks, frameshift mutations, and dN/dS ratios. Estimates for the timing of the transition from functional gene to pseudogene are based on decomposition of mixed dN/dS history into two distinct episodes of evolution under purifying selection and neutral evolution, respectively. The divergence time between Tubulidentata and Afrosoricida (golden moles, tenrecs) + Macroscelidea (elephant shrews) is from Murphy and Eizirik [23]. The age of the oldest aardvark, O. minutus , is from Milledge [25]. doi:10.1371/journal.pgen.1000634.g003
… 
A synthetic interpretation of the history of enamel degeneration in Pholidota (pangolins) based on fossils, phylogenetics, molecular clocks, frameshift mutations, and dN/dS ratios. Estimates for the timing of the transition from functional gene to pseudogene are based on decomposition of mixed dN/dS history into two distinct episodes of evolution under purifying selection and neutral evolution, respectively. The divergence time between Pholidota and Carnivora (79.8 mya) is from Murphy and Eizirik [23]. The divergence time between Manis pentadactyla and M. tricuspis (27.9 mya) is based on molecular dating analyses with ENAM (see Methods). The age of the oldest pangolin, Eomanis from the Eocene Messel deposits of Germany, is , 47 mya [29]. doi:10.1371/journal.pgen.1000634.g004
+2
A synthetic interpretation of the history of enamel degeneration in Pholidota (pangolins) based on fossils, phylogenetics, molecular clocks, frameshift mutations, and dN/dS ratios. Estimates for the timing of the transition from functional gene to pseudogene are based on decomposition of mixed dN/dS history into two distinct episodes of evolution under purifying selection and neutral evolution, respectively. The divergence time between Pholidota and Carnivora (79.8 mya) is from Murphy and Eizirik [23]. The divergence time between Manis pentadactyla and M. tricuspis (27.9 mya) is based on molecular dating analyses with ENAM (see Methods). The age of the oldest pangolin, Eomanis from the Eocene Messel deposits of Germany, is , 47 mya [29]. doi:10.1371/journal.pgen.1000634.g004
… 
Figures - uploaded by Robert W Meredith
Author content
All figure content in this area was uploaded by Robert W Meredith
Content may be subject to copyright.
pgen.10006
34.pdf
Content uploaded by Robert W Meredith
Author content
All content in this area was uploaded by Robert W Meredith
Content may be subject to copyright.
Molecular Decay of the Tooth Gene Enamelin (ENAM) Mirrors the Loss of Enamel in the Fossil Record of Placental Mamma
ls.pdf
Available via license: CC BY 4.0
Content may be subject to copyright.
A preview of the PDF is not available

Supplementary resources (12)

Text S1
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Figure S2
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Dataset S1
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Figure S7
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Table S1
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Figure S8
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Figure S6
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Figure S5
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Figure S4
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Figure S1
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Dataset S2
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
Figure S3
Data
September 2009
Robert W Meredith · John Gatesy · William J. Murphy · Oliver A Ryder · Mark Springer
... Most of these mutations were reported in species that have the least complex enamel such as Mesoplodon bidens (Sowerby's beaked whale), Monodon monoceros (narwhal), Physeter macrocephalus (sperm whale), Kogia spp. (pygmy and dwarf sperm whales), and Delphinapterus leucas (beluga) [31][32][33][34][35]. However, mutations have also been reported in taxa with more complex enamel such as porpoises (Phocoenidae) with intermediate enamel and the killer whale (Orcinus orca) that has prismatic enamel [33][34][35]. ...
... Genes included in this study (ACP4, AMBN, AMELX, AMTN, ENAM, KLK4, MMP20) are shown in Figure 1B and were chosen based on (1) prior studies that reported inactivation of these genes in edentulous (turtles, birds, pangolins, baleen whales, anteaters, Steller's sea cow) and enamelless vertebrates (aardvark, armadillo, sloth), (2) mutations in humans that cause amelogenesis imperfecta, and (3) mutagenesis gene knockout studies in mice [10,24,[31][32][33][34][35][36][37][38][39][40][41][42][43][44]. The tooth-related gene ODAM was also pseudogenized in all odontocete species that were examined by Springer et al. [30]. ...
... Sequences were manually spot-checked for alignment errors using AliView version 1.28 [53]. Alignments were manually screened for different types of inactivating mutations in exons and introns that are regularly inferred from genome sequences including frameshift insertions and deletions (indels), start and stop codon mutations, premature stop codons, intron splice site mutations, exon deletions, and whole gene deletions [31,35,43]. All of these mutations were annotated in Geneious Prime. ...
Molecular Evidence for Relaxed Selection on the Enamel Genes of Toothed Whales (Odontoceti) with Degenerative Enamel Phenotypes
Article
Full-text available
  • Feb 2024
Different species of toothed whales (Odontoceti) exhibit a variety of tooth forms and enamel types. Some odontocetes have highly prismatic enamel with Hunter-Schreger bands, whereas enamel is vestigial or entirely lacking in other species. Different tooth forms and enamel types are associated with alternate feeding strategies that range from biting and grasping prey with teeth in most oceanic and river dolphins to the suction feeding of softer prey items without the use of teeth in many beaked whales. At the molecular level, previous studies have documented inactivating mutations in the enamel-specific genes of some odontocete species that lack complex enamel. At a broader scale, however, it is unclear whether enamel complexity across the full diversity of extant Odontoceti correlates with the relative strength of purifying selection on enamel-specific genes. Here, we employ sequence alignments for seven enamel-specific genes (ACP4, AMBN, AMELX, AMTN, ENAM, KLK4, MMP20) in 62 odontocete species that are representative of all extant families. The sequences for 33 odontocete species were obtained from databases, and sequences for the remaining 29 species were newly generated for this study. We screened these alignments for inactivating mutations (e.g., frameshift indels) and provide a comprehensive catalog of these mutations in species with one or more inactivated enamel genes. Inactivating mutations are rare in Delphinidae (oceanic dolphins) and Platanistidae/Inioidea (river dolphins) that have higher enamel complexity scores. By contrast, mutations are much more numerous in clades such as Monodontidae (narwhal, beluga), Ziphiidae (beaked whales), Physeteroidea (sperm whales), and Phocoenidae (porpoises) that are characterized by simpler enamel or even enamelless teeth. Further, several higher-level taxa (e.g., Hyperoodon, Kogiidae, Monodontidae) possess shared inactivating mutations in one or more enamel genes, which suggests loss of function of these genes in the common ancestor of each clade. We also performed selection (dN/dS) analyses on a concatenation of these genes and used linear regression and Spearman’s rank-order correlation to test for correlations between enamel complexity and two different measures of selection intensity (# of inactivating mutations per million years, dN/dS values). Selection analyses revealed that relaxed purifying selection is especially prominent in physeteroids, monodontids, and phocoenids. Linear regressions and correlation analyses revealed a strong negative correlation between selective pressure (dN/dS values) and enamel complexity. Stronger purifying selection (low dN/dS) is found on branches with more complex enamel and weaker purifying selection (higher dN/dS) occurs on branches with less complex enamel or enamelless teeth. As odontocetes diversified into a variety of feeding modes, in particular, the suction capture of prey, a reduced reliance on the dentition for prey capture resulted in the relaxed selection of genes that are critical to enamel development.
View
... Convergent evolution is a central theme in the history of life on Earth [1,2], and the products of convergence comprise a natural laboratory, complete with replicated experiments, for elucidating regions of the genome that underlie specific phenotypic traits [3][4][5]. Numerous definitions of convergent evolution have been proposed, but at their core, most center on the independent evolution of similar traits in multiple lineages [6]. Examples include the adaptive radiation of cichlid fishes that has resulted in multiple instances of convergence in body and trophic morphology [7]; the convergent evolution of fusiform bodies with similar control surfaces (i.e., fins, flippers, flukes) in various sharks, ichthyosaurs, and cetaceans [8]; convergence of elaborate territorial displays in Anolis lizards on different islands in the Caribbean [9]; and the classic case of convergent morphological evolution between assorted placental and marsupial mammals that includes wolves and thylacines, cats and quolls, anteaters and numbats, mice and marsupial mice, and between placental moles (golden moles, eulipotyphlan moles) and marsupial moles [1,10] ( Figure 1). ...
... Selection (dN/dS) analyses were performed with the codeml program in PAML 4.4 [75]. We performed branch analyses with separate branch categories for background branches, transitional branches, and fully pseudogenic branches [3]. Background branches are functional branches that lack inactivating mutations; transitional branches record the first inactivating mutation in a lineage; and fully pseudogenic branches postdate the first occurrence of an inactivating mutation on an earlier branch. ...
... We used equations from Meredith et al. [3] and divergence times from Meredith et al. [11] for afrotheres and Duchêne et al. [77] for marsupials to estimate the onset of relaxed selection (=neutral evolution) for groups of eye-specific genes, and by proxy the associated phenotypes, in Chrysochloridae and Notoryctes typhlops. Meredith et al. [11] estimated a divergence time of 68.21 million years ago (MYA) for the split between Chrysochloridae and Tenrecidae, and a divergence time of 12.04 MYA for the split between Chrysochloris asiatica and Amblysomus hottentotus. ...
Three Blind Moles: Molecular Evolutionary Insights on the Tempo and Mode of Convergent Eye Degeneration in Notoryctes typhlops (Southern Marsupial Mole) and Two Chrysochlorids (Golden Moles)
Article
Full-text available
  • Oct 2023
Golden moles (Chrysochloridae) and marsupial moles (Notoryctidae) are textbook examples of convergent evolution. Both taxa are highly adapted to subterranean lifestyles and have powerful limbs for digging through the soil/sand, ears that are adapted for low-frequency hearing, vestigial eyes that are covered by skin and fur, and the absence of optic nerve connections between the eyes and the brain. The eyes of marsupial moles also lack a lens as well as retinal rods and cones. Two hypotheses have been proposed to account for the greater degeneracy of the eyes of marsupial moles than golden moles. First, marsupial moles may have had more time to adapt to their underground habitat than other moles. Second, the eyes of marsupial moles may have been rapidly and recently vestigialized to (1) reduce the injurious effects of sand getting into the eyes and (2) accommodate the enlargement of lacrimal glands that keep the nasal cavity moist and prevent the entry of sand into the nasal passages during burrowing. Here, we employ molecular evolutionary methods on DNA sequences for 38 eye genes, most of which are eye-specific, to investigate the timing of relaxed selection (=neutral evolution) for different groups of eye-specific genes that serve as proxies for distinct functional components of the eye (rod phototransduction, cone phototransduction, lens/cornea). Our taxon sampling included 12 afrothere species, of which two are golden moles (Amblysomus hottentotus, Chrysochloris asiatica), and 28 marsupial species including two individuals of the southern marsupial mole (Notoryctes typhlops). Most of the sequences were mined from databases, but we also provide new genome data for A. hottentotus and one of the two N. typhlops individuals. Even though the eyes of golden moles are less degenerate than the eyes of marsupial moles, there are more inactivating mutations (e.g., frameshift indels, premature stop codons) in their cone phototransduction and lens/cornea genes than in orthologous genes of the marsupial mole. We estimate that cone phototransduction recovery genes were inactivated first in each group, followed by lens/cornea genes and then cone phototransduction activation genes. All three groups of genes were inactivated earlier in golden moles than in marsupial moles. For the latter, we estimate that lens/cornea genes were inactivated ~17.8 million years ago (MYA) when stem notoryctids were burrowing in the soft soils of Australian rainforests. Selection on phototransduction activation genes was relaxed much later (5.38 MYA), during the early stages of Australia’s aridification that produced coastal sand plains and eventually sand dunes. Unlike cone phototransduction activation genes, rod phototransduction activation genes are intact in both golden moles and one of the two individuals of N. typhlops. A second marsupial mole individual has just a single inactivating mutation in one of the rod phototransduction activation genes (PDE6B). One explanation for this result is that some rod phototransduction activation genes are pleiotropic and are expressed in extraocular tissues, possibly in conjunction with sperm thermotaxis.
View
... Genetic association studies in humans with dental diseases and mouse knockout models have led to a robust understanding of the genetics underlying tooth development (Meredith et al., 2014;Smith et al., 2017), and comparative genomic analyses of edentulous (toothless) and enamelless vertebrates have revealed that many of these same dental genes were deleted or have eroded into unitary pseudogenes. Indeed, the list of documented dental pseudogenes in such vertebrates includes those encoding (1) enamel matrix proteins (EMPs), which provide a protein scaffold for the seeding of hydroxyapatite crystals during enamel development (ENAM [enamelin], AMELX [amelogenin], AMBN [ameloblastin]) (Choo et al., 2016;Delsuc et al., 2015;Meredith et al., 2014Meredith et al., , 2013Meredith et al., , 2009Sire et al., 2008), (2) a metalloproteinase that processes these matrix proteins into their mature forms (MMP20 [enamelysin]) (Meredith et al., 2011a(Meredith et al., , 2014, (3) other proteins expressed in both enamel-forming ameloblasts and enamel-contacting gingiva (AMTN [amelotin], ODAM [odontogenic ameloblast-associated]) (Gasse et al., 2012;Meredith et al., 2014;Springer et al., 2019), (4) proteins of unknown function but showing clear associations with enamel formation (ACP4 [acid phosphatase 4; formerly called ACPT], ODAPH [odontogenesis-associated phosphoprotein; formerly called C4orf26]) (Mu et al. 2021;Sharma et al., 2018;Springer et al., 2016), and (5) a protein that contributes to the dentin matrix (DSPP [dentin sialophosphoprotein]) (Meredith et al., 2014;Sire et al., 2008;McKnight and Fisher 2009). ...
... To study patterns of dental gene loss in xenarthrans, we assembled a dataset of 11 dental genes: nine genes have well-characterized functions and/or expression patterns tied to tooth development and are frequently pseudogenized in edentulous and enamelless taxa (ACP4, AMBN, AMELX, AMTN, DSPP, ENAM, MMP20, ODAM, ODAPH;Choo et al., 2016;Delsuc et al., 2015;Gasse et al., 2012;McKnight and Fisher, 2009;Meredith et al., 2014Meredith et al., , 2013Meredith et al., , 2011aMeredith et al., , 2009Mu et al., 2021;Sharma et al., 2018;Sire et al., 2008;Smith et al., 2017;Springer et al., 2019Springer et al., , 2016, and two other genes (DMP1, MEPE) are expressed in dentin (Sun et al., 2011;Gullard et al., 2016). Our taxonomic coverage included 31 xenarthran species (four anteaters, six sloths, seven dasypodid armadillos, 14 chlamyphorid armadillos) plus 25 outgroup species spanning the remaining three superorders of placental mammals. ...
... Next, using the branch model approach, we allowed ω to vary across the phylogeny in a multi-ratio model with branch labels set for (a) each set of branches within a clade that post-date the minimum gene inactivation date inferred from shared inactivation mutations, (b) each branch that coincides with inferred gene inactivation, and (c) certain branches that predate gene inactivation, often grouped together with multiple such branches. Note that this does not correspond to a free ratio model, but rather follows a previously described approach (Meredith et al., 2009). In every case, when taxon representation was sufficient, we set separate branch categories for stem Xenarthra, stem Pilosa, stem Cingulata, stem Chlamyphoridae, and stem Dasypodidae. ...
View
... correspond to a free ratio model, but rather follows a previously described approach (Meredith et al., 2009). 341 ...
... ω < 1 suggests conservation of protein sequence (purifying 661 selection) on average across the gene on that branch, ω > 1 is consistent with change in protein function 662 (positive selection), and ω = 1 is associated with relaxed selection, which is the pattern expected for 663 pseudogenes. However, on a phylogenetic branch that has a mixed history, such as purifying selection 664 followed by relaxed selection, ω should be intermediate between the average strength of selection and one 665 (Meredith et al., 2009). As such, we estimated the average background ω, and tested whether key branches 666 ...
... Third, while we found 775 evidence of elevated dN/dS for a single gene (ACP4) on the stem xenarthran branch, this estimate was only 776 marginally significant and the descendant Cingulata branch showed purifying selection on this gene. By 777 contrast, we found five genes showing statistically significant purifying selection on this branch, three of 778 which are enamel-specific genes with widespread patterns of pseudogenization in vertebrates with dental 779 regression (AMELX, ENAM, MMP20) (Meredith et al., 2009(Meredith et al., , 2011a(Meredith et al., , 2013(Meredith et al., , 2014Choo et al., 2016). Fourth, 780 the same can be said for the stem armadillo branch, on which five genes were also statistically consistent 781 ...
View
... We conducted analyses for both PADI3 and S100A3, with separate dN/dS categories for functional branches lacking loss-of-function mutations, for fully pseudogenic branches that emerged after a loss-of-function mutation on a previous branch, and for each transitional branch that marks the initial occurrence of a loss-of-function mutation (Meredith et al. 2009;Springer et al. 2021). Although we did not identify a shared loss-of-function mutation in S100A3 in the cetaceans, we treated the S100A3 branches in the cetaceans as fully pseudogenic. ...
... We used the method described in Meredith et al. (2009) to estimate pseudogenization times. Briefly, the transitional branch has both functional and pseudogenic dN/dS values, and the transitional time is estimated as the pseudogenization time. ...
Pseudogenization of the Hair-Related Genes PADI3 and S100A3 in Cetaceans and Hippopotamus amphibius
Article
Full-text available
  • Oct 2023
  • J MOL EVOL
Hair-related genes in mammals play important roles in the development and maintenance of hair and other keratinous structures in mammals. The peptidyl arginine deiminase 3 (PADI3) gene encodes an enzyme that catalyzes the conversion of arginine residues to citrulline. The S100 calcium binding protein A3 (S100A3) gene encodes a protein that is highly expressed in the hair cuticle and contains arginine residues that are converted to citrullines by PADI enzymes. In this study, we investigated the pseudogenization events of PADI3 and S100A3 in cetaceans and Hippopotamus amphibius. We found that PADI3 underwent three independent pseudogenization events during cetacean evolution, in baleen whales, toothed cetaceans other than Physeter catodon, and P. catodon. Notably, the entire PADI3 gene is absent in the baleen whales. Pseudogenization of S100A3 occurred independently in cetaceans and H. amphibius. Interestingly, we found that in cetaceans S100A3 underwent pseudogenization before PADI3, suggesting that differential selection pressures were acting on the two genes. Our findings provide valuable insights into the molecular evolution of these genes in cetaceans and hippopotamuses, highlighting their importance for understanding the evolution of hair-related genes.
View
... Hatched boxes indicate genes found in only one of the two databases. earlier findings [21,22], including the debated convergent evolution of enamel-related genes [23,24] (Figure 2). We found that the presence of enamel-related SCPP genes correlated with the existence of teeth (Figure 1). ...
Emergence of saliva protein genes in the secretory calcium-binding phosphoprotein (SCPP) locus and accelerated evolution in primates
Preprint
Full-text available
  • Feb 2024
Genes within the secretory calcium-binding phosphoprotein (SCPP) family evolved in conjunction with major evolutionary milestones: the formation of a calcified skeleton in vertebrates, the emergence of tooth enamel in fish, and the introduction of lactation in mammals. The SCPP gene family also contains genes expressed primarily and abundantly in human saliva. Here, we explored the evolution of the saliva-related SCPP genes by harnessing currently available genomic and transcriptomic resources. Our findings provide insights into the expansion and diversification of SCPP genes, notably identifying previously undocumented convergent gene duplications. In primate genomes, we found additional duplication and diversification events that affected genes coding for proteins secreted in saliva. These saliva-related SCPP genes exhibit signatures of positive selection in the primate lineage while the other genes in the same locus remain conserved. We found that regulatory shifts and gene turnover events facilitated the accelerated gain of salivary expression. Collectively, our results position the SCPP gene family as a hotbed of evolutionary innovation, suggesting the potential role of dietary and pathogenic pressures in the adaptive diversification of the saliva composition in primates, including humans.
View
... aardvarks, armadillos, sloths) and edentulous tetrapods (e.g. baleen whales, anteaters, pangolins, birds, turtles) [3,4,[17][18][19][20], pointing to their specific requirements in odontogenesis. Inactivation of these genes is also associated with congenital diseases in humans, particularly amelogenesis imperfecta and dentinogenesis imperfecta, and similar phenotypes in mouse models [21]. ...
From teeth to pad: tooth loss and development of keratinous structures in sirenians
Article
Full-text available
  • Nov 2023
Sirenians are a well-known example of morphological adaptation to a shallow-water grazing diet characterized by a modified feeding apparatus and orofacial morphology. Such adaptations were accompanied by an anterior tooth reduction associated with the development of keratinized pads, the evolution of which remains elusive. Among sirenians, the recently extinct Steller's sea cow represents a special case for being completely toothless. Here, we used μ-CT scans of sirenian crania to understand how motor-sensor systems associated with tooth innervation responded to innovations such as keratinized pads and continuous dental replacement. In addition, we surveyed nine genes associated with dental reduction for signatures of loss of function. Our results reveal how patterns of innervation changed with modifications of the dental formula, especially continuous replacement in manatees. Both our morphological and genomic data show that dental development was not completely lost in the edentulous Steller's sea cows. By tracing the phylogenetic history of tooth innervation, we illustrate the role of development in promoting the innervation of keratinized pads, similar to the secondary use of dental canals for innervating neomorphic keratinized structures in other tetrapod groups.
View
... For instance, the monotypic family Manitherionyssidae, which is currently restricted to pangolins, has no fossil evidence of mesostigmatids. These unusual animals split from their sister groups in the late Cretaceous slightly earlier than previously believed, according to molecular evidence (Meredith et al., 2009). The fossil record dates back to the Eocene. ...
Progression of parasitism from phoresy in mites
Article
Full-text available
  • Aug 2023
The mites are the smallest (less than a millimeter in length), the most diverse, and the most common of all arachnids. Mites are ubiquitous and inhabit all known terrestrial, marine, and freshwater habitats, including arctic and alpine extremes, tropical plains and desert barrens, and surface and mineral soils (Dunlop and Alberti, 2008). More than 55,000 species have been described up to date, accounting for 5% of all living species today. Mites are experts at transport with the aid of large animals, mostly insects. It is a temporary relationship called phoresy that allows the mites to exploit scarce resources. Phoresy in the subclass Acari includes insects that feed on carriers. Phoresy evolved from free-living ancestors. The primary waste material used by floating mites appears to be rotting logs. However, rapid changes in the later life stage allowed the development of short-term resources. Although phoresy is a form of social interaction, most interact with mites. These relationships can be very complex and context-specific, but they often use the vector's sources or descendants (Seeman and Walter, 2023). The switch from phoretic to parasitism seems popular, but the scientific evidence for a switch from phoretic to permanent parasitism seems to be lacking.
View
ENAM Mutations Can Cause Hypomaturation Amelogenesis Imperfecta
Article
  • May 2024
  • J DENT RES
Amelogenesis imperfecta (AI) is a diverse group of inherited diseases featured by various presentations of enamel malformations that are caused by disturbances at different stages of enamel formation. While hypoplastic AI suggests a thickness defect of enamel resulting from aberrations during the secretory stage of amelogenesis, hypomaturation AI indicates a deficiency of enamel mineralization and hardness established at the maturation stage. Mutations in ENAM, which encodes the largest enamel matrix protein, enamelin, have been demonstrated to cause generalized or local hypoplastic AI. Here, we characterized 2 AI families with disparate hypoplastic and hypomaturation enamel defects and identified 2 distinct indel mutations at the same location of ENAM, c588+1del and c.588+1dup. Minigene splicing assays demonstrated that they caused frameshifts and truncation of ENAM proteins, p.Asn197Ilefs*81 and p.Asn197Glufs*25, respectively. In situ hybridization of Enam on mouse mandibular incisors confirmed its restricted expression in secretory stage ameloblasts and suggested an indirect pathogenic mechanism underlying hypomaturation AI. In silico analyses indicated that these 2 truncated ENAMs might form amyloid structures and cause protein aggregation with themselves and with wild-type protein through the added aberrant region at their C-termini. Consistently, protein secretion assays demonstrated that the truncated proteins cannot be properly secreted and impede secretion of wild-type ENAM. Moreover, compared to the wild-type, overexpression of the mutant proteins significantly increased endoplasmic reticulum stress and upregulated the expression of unfolded protein response (UPR)–related genes and TNFRSF10B, a UPR-controlled proapoptotic gene. Caspase, terminal deoxynucleotidyl transferase UTP nick-end labeling (TUNEL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays further revealed that both truncated proteins, especially p.Asn197Ilefs*81, induced cell apoptosis and decreased cell survival, suggesting that the 2 ENAM mutations cause AI through ameloblast cell pathology and death rather than through a simple loss of function. This study demonstrates that an ENAM mutation can lead to generalized hypomaturation enamel defects and suggests proteinopathy as a potential pathogenesis for ENAM-associated AI.
View
Whole-genome Sequencing Reveals Autooctoploidy in Chinese Sturgeon and Its Evolutionary Trajectories
Article
Full-text available
  • Dec 2023
The order Acipenseriformes, which includes sturgeons and paddlefishes, represents “living fossils” with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploidy fishes.
View
Whales and even-toed ungulates (Cetartiodactyla)
Chapter
  • Apr 2009
Whales (Cetacea) and even-toed ungulates (“Artiodactyla,” not a natural group) are represented by 290 extant species (1), and have been grouped into 20–25 families within the placental Order Cetartiodactyla (Fig. 1). Extinct diversity is well represented in the clade, with about six extinct genera for every genus that contains extant species (2). 7is rich fossil record has facilitated molecular clock analyses (3–14), but phenotypic diversity in the group is extensive and has confounded systematic studies. Cetartiodactylans range in body size from the tiny 4 kg mouse deer, Tragulus javanicus, to the enormous 190,000 kg Blue Whale, Balaenoptera musculus (1). It is oJen di1cult to assess homology of structures in organisms that are as divergent as these in terms of anatomical organization, mass, and ecological specialization. Among taxa with living representatives, McKenna and Bell (2) recognized 11 families of Cetacea and 10 families of “Artiodactyla.” 7ree additional family-level groups (Eschrichtiidae, Neobalaenidae, and Kogiidae) are commonly accepted. Here I review the phylogenetic relationships and divergence times of the families of Cetartiodactyla (Fig. 2).
View
REPTILIAN VIVIPARITY AND DOLLO'S LAW
Article
  • Oct 1998
  • EVOLUTION
It has been suggested repeatedly that the evolutionary transition from oviparity (egg-laying) to viviparity (live-bearing) in reptiles is irreversible. However, these adaptive arguments have yet to be tested by detailed examination of the phylogenetic distribution of oviparity and viviparity across a broad range of taxa. Using available data on reproductive modes and phylogenetic relationships within reptiles, we here quantify the numbers and directions of evolutionary transitions between oviparity and viviparity. Phylogenetic relationships among three diverse squamate groups (scincid lizards, colubrid snakes, elapid snakes) are currently inadequately known for inclusion in this study Among the remaining reptiles, oviparity has given rise to viviparity at least 35 times. Five possible instances of reversals (from viviparity to oviparity) are identified, but closer examination indicates that all have weak empirical support (i.e., they could be "unreversed" with little loss in parsimony, and/or are based on poorly substantiated phylogenetic hypotheses). Viviparity is clearly more frequently (and presumably easily) gained than lost in several disparate groups so far examined (reptiles, fishes, polychaete worms); this evolutionary bias should be considered when reproductive mode is optimized on a phylogeny or employed in phylogenetic reconstruction.
View
View
View
View
View
View
View
View
View