Forsyth Institute scientist Peter Jezewski, DDS, Ph.D., says that duplication and diversification of protein regions ('modules') within ancient master control genes is key to the understanding of certain birth disorders. Tracing the history of these changes within the proteins coded by the Msx gene family over the past 600 million years has also provided additional evidence for the ancient origin of the human mouth.
Jezewski published the study examining the Msx family that has ancient roots as a master control gene for patterned embryonic growth. Previous work identified mutations within the human MSX1 gene in two different birth disorders: either cleft lip and palate or skin derivative disorders ('ectodermal dysplasias') that include tooth and nail malformations. The mutations associated with the more severe clefting disorder are found within unique portions of the MSX protein, thus providing the first molecular explanation for this disease pattern. This work may eventually enable genetically susceptible families with environmental risk factors to prevent these common birth disorders.
Jezewski is a research associate in the Department of Cytokine Biology at the Forsyth Institute and an instructor, Department of Oral Medicine, Infection and Immunity at the Harvard School of Dental Medicine. The Jezewski lab studies inheritance patterns of human oral-facial diseases particularly complex birth disorders as well as forms of aggressive periodontitis.
Cleft lip and palate is one of the most common birth defects. Both genes and environment contribute to this condition. "If we can learn more about genetic susceptibility of these families, we can start to examine how environmental factors, like maternal smoking, may contribute to their manifestation," says Dr. Jezewski. "This information could lead to recommendations for appropriate behavioral changes within families who are genetically at risk."
The research team performed a battery of evolutionary analyses on 46 Msx proteins from a diverse collection of animals, ranging from sponges to humans. This analysis identified human sequence variants in Msx likely to underlie disease, and indicated why mutations in the same gene can lead to either orofacial clefting or ectodermal dysplasias.
These clinical insights were gleaned from work demonstrating that certain portions of the Msx proteins have remained constant over extremely long periods of time (>600 million years) while other Msx protein modules had duplicated and then subsequently diverged within the duplicated Msx sister genes, a previously unrecognized avenue for the evolution of morphological innovation.
They say these observations will help to prioritize future clinical and functional research on these disease mutations. An outgrowth of these insights was the realization that the highly conserved protein modules that make up the Msx protein help to define a class of animal specific master control genes that each go on to specifically pattern the body plan of all modern animals.
This work was supported in part by research grants from the National Institute of Dental and Craniofacial Research.
The study, "Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers," was published in BMC Evolutionary Biology January 14, 2009. This research was led by Dr. Peter Jezewski at The Forsyth Institute, and was conducted with collaborators at Boston University, Drs. John Finnerty and Maureen Mazza.
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- How Gut Bacteria Ensure A Healthy Brain – and Could Play A Role In Treating Depression
- Researchers Created A Laser Bullet To See What It Would Look Like - And Here It Is
- The Strange Organic Molecules In Titan's Atmosphere
- Erupting Bardarbunga Volcano In Iceland Sits On A Massive Magma Hot Spot
- We're Too Late To Prevent 137,000 More Ebola Cases, Says Epidemiology Paper
- ASTEROIDS Act: Who Owns Space?
- The Quote Of The Week - Shocked And Disappointed
- " Obviously 300% more fish farming means more illnesses and more antibiotic use.Is it really..."
- "thermocamera caught surface temperatire, as discovered out by Giancarlo here. ..."
- "I would like to believe that the E-Cat really produces a lot of excess heat energy, but I ran across..."
- "Because there are only 2?..."
- "I found the AMO/PDO charts to be very broad, and hard to tell (at least with the limited knowledge..."
- How to sell a toxic pesticide the smart way–call it organic
- Leftist dystopia? Anti-technology fever animates opposition to GMOs and other ‘disruptive’ technologies
- CDC faced a nearly impossible balancing act with Ebola, and failed
- Why Chobani reversed course, making yoghurt only from milk from cows not fed GMO grain
- Monterey, California, hotbed of anti-GMO activism, home to new GMO corn farm
- Evolution is sometimes messy or even outright ridiculous