Mineralized tissue and vertebrate evolution: The secretory calcium-binding phosphoprotein gene cluster

Abstract

Gene duplication creates evolutionary novelties by using older tools in new ways. We have identified evidence that the genes for enamel matrix proteins (EMPs), milk caseins, and salivary proteins comprise a family descended from a common ancestor by tandem gene duplication. These genes remain linked, except for one EMP gene, amelogenin. These genes show common structural features and are expressed in ontogenetically similar tissues. Many of these genes encode secretory Ca-binding phosphoproteins, which regulate the Ca-phosphate concentration of the extracellular environment. By exploiting this fundamental property, these genes have subsequently diversified to serve specialized adaptive functions. Casein makes milk supersaturated with Ca-phosphate, which was critical to the successive mammalian divergence. The innovation of enamel led to mineralized feeding apparatus, which enabled active predation of early vertebrates. The EMP genes comprise a subfamily not identified previously. A set of genes for dentine and bone extracellular matrix proteins constitutes an additional cluster distal to the EMP gene cluster, with similar structural features to EMP genes. The duplication and diversification of the primordial genes for enamel͞dentine͞bone extracellular matrix may have been important in core vertebrate feeding adaptations, the mineralized skeleton, the evolution of saliva, and, eventually, lactation. The order of duplication events may help delineate early events in mineralized skeletal formation, which is a major characteristic of vertebrates.

Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

“…These absences might therefore mirror the evolution of the vomeronasal organ and mammary glands in mammals, and the loss of teeth in birds. The presence in fish of enamel-associated genes and their absence in chicken, together with absence of chicken casein and salivary-associated genes, which all cluster together in mammalian genomes, is consistent with a previous suggestion 73 that these have all descended, by gene duplication and rapid sequence diversification, from a common ancestor, possibly an enamel-associated gene.…”

Mineralization and bone regeneration using a bioactive elastin-like recombinamer membrane

“…To our knowledge, this is the first study that demonstrates enhanced bone regeneration using ELRs and the use of a statherin analog known to modulate mineralization in enamel for bone regeneration. A po-tential explanation for this finding may lie in the fact that statherin found in saliva and proteins found in bone, all of which regulate the growth of CaP, descend from a set of genes that have a common ancestor [45]. This relation may help explain why the SN A 15 frag-ment found to control enamel mineralization [36], is also efficiently promoting bone formation as observed in this study.…”

The evolution of milk secretion and its ancient origins

“…The proposal that mammary secretion has an ancient origin and long evolutionary history (Oftedal, 2002a and2002b) is increasingly accepted, especially in the face of supportive molecular evidence (Kawasaki and Weiss, 2003;Vorbach et al, 2006;Brawand et al, 2008;McClellan et al, 2008;Capuco and Akers, 2009;Lemay et al, 2009;Lefevre et al, 2010;Kawasaki et al, 2011). It is now possible to formulate a more detailed scenario by which the secreted fluid came to resemble in form and function what we now know as milk.…”

“…These proteins, termed secretory calcium-binding phosphoproteins (SCPPs), are secreted by secretory epithelial cells or cells derived from underlying ectomesenchymal cells, and have an ancient history in the evolution of mineralized vertebrate tissues (Kawasaki and Weiss, 2003;Kawasaki, 2009). As unfolded proteins, all SCPPs are low in cysteine and therefore cystine disulfide bridges, and a subclass of the proteins (P/Q-rich SCPPs), including the caseins, are particularly rich in proline and glutamine (Kawasaki and Weiss, 2003;Kawasaki et al, 2011).…”

“…These proteins, termed secretory calcium-binding phosphoproteins (SCPPs), are secreted by secretory epithelial cells or cells derived from underlying ectomesenchymal cells, and have an ancient history in the evolution of mineralized vertebrate tissues (Kawasaki and Weiss, 2003;Kawasaki, 2009). As unfolded proteins, all SCPPs are low in cysteine and therefore cystine disulfide bridges, and a subclass of the proteins (P/Q-rich SCPPs), including the caseins, are particularly rich in proline and glutamine (Kawasaki and Weiss, 2003;Kawasaki et al, 2011). On the basis of the relative locations and structures of exons of these P/Q-rich SCPPs, as well as their phylogenetic distribution, Kawasaki et al (2011) proposed that the a-and b-caseins derived via gene duplication and exon changes from an ancestral gene (CSN1/2) that derives from another SCPP gene, either ODAM or SCPPPQ1 (which itself is derived from ODAM ), whereas k-casein derives from the SCPP gene FDCSP (which is also derived from ODAM ).…”