The Power of Genomics

In this age of relatively inexpensive DNA sequencing and genomics—the comparative study of genes across species—scientists for the first time can parse the evolutionary record of genes and their proteins and assemble remarkable genealogical insights. In oral biology, one of the most fascinating of these unfolding genomic stories involves dentin matrix protein-1 (DMP1) and dentin sialophosphoprotein (DSPP). Both belong to a currently 5-member family of noncollagenous, extracellular proteins called SIBLINGs, short for "small integrin-binding ligand, N-linked glycoprotein." These proteins seem to play an important role in regulating the mineralization of collagen fibers that, in turn, results in the production of bone and dentin. In the late 1990s, researchers discovered that the SIBLING genes, including DMP1 and DSPP, are clustered on human chromosome 4, which suggests a possible shared evolution. When researchers looked deeper into the structure of the SIBLING gene sequences, they noticed a profoundly interesting possibility. The patterns written into the sequence indicated that the SIBLINGs likely were the products of an ancient gene duplication, from which each gene followed its own evolutionarily divergent path to its functional present.
A National Institute of Dental and Craniofacial Research (NIDCR) scientist has tracked this genomic story with a strong focus on DMP-1 and DSPP. As published online on May 9, in the journal Cells Tissues Organs, the scientist proposes that an ancient, amphibian-like DMP1 gene was duplicated in a common ancestor of reptiles and mammals. The duplicated gene, consisting of simple tandem repeat DNA sequences, permanently integrated on one end of the SIBLING gene cluster. That led to at least 2 evolutionarily divergent outcomes: One, reptiles began using the portion of the duplicated DMP1-like gene that geographically flanks a gene called SPARCL1. The reptiles then transcribed the sequence near SPARCL1 and produced a new protein, the function of which is undetermined. Two, the entire mammalian lineage, which of course includes humans, transcribed the opposite end of the duplicated DMP-1 gene, away from SPARCL1 and flanking another gene called IBSP. This alternate site of replication, in turn, produced a protein that evolved separately into a DSPP-like protein, a precursor of today's DSPP in human dentin.
"Both classes of animals [reptile and mammal] retained their second copy of the DMP1 gene presumably to continue the original functions of this more ancient SIBLING gene product," the author explained. Interestingly, the scientist also looked at the SIBLING cluster of the chicken. As a bird, chickens fall between reptile and mammal on the evolutionary ladder and notably are toothless, meaning they have no dentin and thus no need for DSPP. The scientist found that chickens seem to have lost the DSPP gene completely, although vestiges of the gene sequence may remain as an artifact of the bird's shared evolution with a common ancestor of the reptile. The challenge now is to drill down deeper into the sequence and determine if faint remnants of the DSPP sequence are indeed present, which would help to support the proposed evolutionary model. The scientist noted that research on the evolutionary origins of SIBLING proteins will be critical in determining their precise roles in bone and dentin formation and in learning to mimic their structure and function to better regenerate these tissues in disease. The hope is others will join the hunt—and help solve the mystery.


(Source: NIDCR Science News in Brief, May 18, 2011)