DMP1 and DSPP: Evidence for Duplication and Convergent Evolution of Two SIBLING Proteins

Abstract

Since first being proposed as a tandem gene family in 2001, the relatedness of the 5 SIBLING proteins (BSP, DMP1, DSPP, MEPE, and SPP1/OPN) has predominantly depended on arguments involving shared intron/exon properties as well as conserved protein biochemical properties (e.g. unstructured and acidic) and specific peptide motifs (e.g. phosphorylation and integrin-binding RGD). This report discusses the evidence that an ancient DMP1 gene underwent a simple duplication in the common ancestor of mammals and reptiles and then separately evolved into DSPP-like paralogs in the 2 classes. Genomic sequence analyses show that different copies of the original DMP1 duplication process were selected by mammalian and reptilian (anole lizard) classes to acquire genetically different but biochemically similar phosphoserine-rich repeat domains by convergent evolution. Mammals, for example, expanded phosphoserine motifs encoded exclusively using motifs containing AGC/T serine codons while the reptile line’s repeats also used TCN-encoding serine codons. A similar analysis of the origins of the other 4 SIBLINGs will require even more detailed analysis as genome sequences of various fish and amphibia become available.

Adaptive evolution of the matrix extracellular phosphoglycoprotein in mammals

“…This result is concordant with previous studies [5,29-32] that show the likely presence of two genes belonging to the SIBLING family in teleost fishes but not a MEPE orthologue. Mammals and reptiles are the only tetrapod lineages with all five SIBLING family genes (Figure 1), as previously suggested [28,29]. …”

Retraction: Products of dentin matrix protein-1 degradation by interleukin-1β-induced matrix metalloproteinase-3 promote proliferation of odontoblastic cells

“…Because DMP-1 belongs to the SIBLING family (36), it is speculated that the RGD sequence may be essential for cell proliferation. Dentin sialophosphoprotein (DSPP) and DMP-1 share many similarities in both their gene and protein structures, and it is now believed that DSPP arose from DMP-1 by a gene duplication event (37). DSPP and DMP-1 are both cleaved into two protein chains; the N-terminal regions are proteoglycans that contain chondroitin sulfate chains, and the C-terminal regions are highly phosphorylated (38)(39)(40).…”

Intrinsically disordered proteins and biomineralization

“…OPN, BSP, DSPP and matrix extracellular phosphor glycoprotein (MEPE), dentin matrix protein-1 (DMP1) are all part of the SIBLING protein gene family, where SIBLING indicates small integrin-binding ligand N-linked glycoproteins. They are all found on human chromosome 4, mouse chromosome 5, and have many sequence similarities [29]. They all include repeat sequences with groups capable of phosphorylation and the presence of multiple aspartate or glutamate repeats.…”