Bone, enamel, dentine, milk & saliva share gene family

July 23, 2004

Fish and mammal teeth are not created equal. Sometime after the move from spineless to having a backbone, the family of genes that controls tissue mineralization evolved to produce mammalian tooth enamel, bones and dentine, but fish enameloid developed from different genes, according to Penn State researchers.

"We also suggest that mammalian enamel is distinct from fish enameloid," the researchers reported in this week's online edition of the Proceedings of the National Academy of Sciences. "The similar nature as a hard structural overlay on exoskeleton and teeth is because of convergent evolution." The researchers include Dr. Kazuhiko Kawasaki, senior research associate and Dr. Kenneth W. Weiss, the Evan Pugh Professor of biological anthropology and genetics, Penn State and Tohru Suzuki, professor of agricultural science, Tohoku University, Japan.

While similar structures and traits are often similar because they come from the same genetic basis, it is not unusual to have physical traits that look alike and serve the same purpose, developed from completely unrelated genes.

The genes responsible for bones, enamel, dentine, milk and saliva in most vertebrates belong to the same family; that is, they descend from a common ancestral gene, and for the most part, reside on the same chromosome. These genes are all responsible for calcium binding; whether it is the growth of bone on cartilage, tooth components like enamel and dentine, or production of calcium rich milk and saliva. However, all calcium-binding genes do not exist in all vertebrates.

"Birds have a gene to make hard egg shells, but they do not have genes for making tooth components," says Kawasaki. "Birds probably lost the enamel gene so long ago that there would be no trace of it."

The researchers have traced the development of these calcium-binding genes to a gene, SPARC, that existed before the split occurred between invertebrates and vertebrates during the Precambrian, 500 to 600 million years ago. Sometime after vertebrates arose, a gene called SPARCL1, or SPARC-like 1, developed and this gene is the ancestor of the family of genes that produce the wide variety of mineralized tissues.

Gene families develop because of tandem gene duplication, which occurs when two copies of one gene are copied onto a new chromosome. This error in duplication allows changes to occur in one copy of the gene, while the other copy remains unchanged and preserves the gene's original function. Over time, the individual gene function slowly diverges.

"In any species, some of the duplicate genes could be incomplete or nonfunctional," says Kawasaki. "Others may be become specialized genes coding for things that exist in other vertebrates such as eggshell."

Penn State researchers were originally looking in this chromosome region for a genetic explanation of baboon tooth shape, where they found a series of genes with similar structures, but that all were involved in calcium binding.

Kawasaki used existing data on humans, mice, chicken and zebra fish along with data collected from the DNA of fugu or puffer fish to investigate this chromosome region.

"We also used our original fugu fish data to confirm that the databases were giving us the correct results," says Kawasaki.

The researchers used messenger RNA, the substance that contains the information for producing proteins to reverse engineer DNA that codes for these proteins. This copy DNA can be used to locate the original gene on the chromosome. Except for one of the three genes that codes for mammalian tooth enamel, all the other genes are found in the same area of the same chromosome. One of the enamel genes, AMEL, is found on the X and Y chromosomes in humans.

The gene that codes for fish enameloid however, is not related to this gene family and is not found on the same chromosome.

"Muscles, guts, nerves exist in both invertebrates and vertebrates," says Weiss. "But mineralized tissues such as bones, enamel and dentine are what make vertebrates different."

The split between invertebrates and vertebrates occurs during a time when there is a very spotty fossil record. Most estimates of the timing are done by molecular clock calculations.

The appearance of these mineral tissue genes after the split can shed light on the murky period when creatures developed backbones for internal support, sharp teeth for eating and protection, hard shells to protect developing young and milk to nurture them until they could use their teeth to catch and consume dinner.

"Now we are going to look to see if these genes are expressed in embryos when and where they are supposed to be expressed," says Weiss.
-end-
The National Science Foundation supported this work.

Penn State

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