Navigation Links
First study hints at insights to come from genes unique to humans
Date:3/21/2008

St. Louis, March 21, 2008 Among the approximately 23,000 genes found in human DNA, scientists currently estimate that there may be as few as 50 to 100 that have no counterparts in other species. Expand that comparison to include the primate family known as hominoids, and there may be several hundred unique genes.

Despite the distinctive contributions these genes likely make to our species, little is known about the roles they play. Now scientists at Washington University School of Medicine in St. Louis have produced the first detailed analysis of the cellular functions of a hominoid-only gene, TBC1D3. They affirmed earlier evidence linking the gene to cancer, showing that TBC1D3's protein can keep cellular growth factors active and helps turn on RAS, a protein that is active in a third of all human cancers.

"I was astounded at how little attention has been given to human-specific genes, which make us what we are and could potentially offer a great deal of insight into human physiology," says senior author Philip D. Stahl, Ph.D., the Edward Mallinckrodt Jr. Professor and head of Cell Biology and Physiology. "In addition, certain pathogens, such as the malaria parasite, have human specific-components in their infection cycle. Human-only genes could offer us unique insights into how the parasites take advantage of us and possibly provide potent new avenues for fighting back."

The paper appears online in The Journal of Biological Chemistry.

When scientists want to learn more about the function of a gene, they frequently disable or delete the gene in a laboratory animal and then look to see how the loss changes the animal. That won't be possible with genes unique to humans, Stahl notes. Researchers will have to resort to altering the genes' functions in human cell lines, or transplanting them into animals to see what effects they have.

TBC1D3 was originally identified by other scientists as a likely contributor to breast cancer. At the time of its discovery, researchers linked its protein to endocytosis, a process cells use to take in material from their surface.

Endocytosis plays an important role in the Stahl laboratory. His group studies how growth factor receptors, proteins important for both normal and cancerous growth, are turned on and off. Found on the surfaces of cells, growth factor receptors turn on when they bind to a growth factor protein. To turn them off, cells take in the combined receptor-protein through endocytosis and put it through a number of different processes before finally breaking down the growth factor receptor.

When Stahl and colleagues determined in 2006 that the TBC1D3 gene is only found in hominoids, their curiosity was piqued. Evolution, Stahl notes, naturally tends to retain genes involved in the most important components of metabolism. If one of these genes mutated too dramatically, that would lead to an organism so sickly that it wouldn't survive long enough to perpetuate the mutation in its descendants. So evolution "conserves" these genes, retaining them largely unchanged as one species evolves into another.

Therefore, if the genome is compared to an automobile, human-only genes are unlikely to be adding new wheels. But they could, for example, be contributing a new anti-lock braking system: a regulatory function that fine-tunes essential processes originally established millennia ago in other species.

Stahl found evidence that this is the case in TBC1D3. Human DNA has eight copies or paralogs of the TBC1D3 gene. His lab showed that the increased levels of the protein made by one of the paralogs makes human cells grow more rapidly. When they transplanted the gene for the protein into mouse cells, it had the same effect.

A closer look showed that the protein from the TBC1D3 paralog delays a process that labels growth factor receptors for breakdown, prolonging the time that their signal is active.

He also found evidence that the protein was helping to activate RAS, another gene whose protein is commonly found in human cancers.

Stahl and his colleagues plan additional research to learn whether the other paralogs of TBC1D3 have different roles. He also has several ideas for learning more about the functions of human-only genes.

"We might try an organ-by-organ approach, looking to see if any genes specific to a particular organs, such as fat, are specific to humans," he says. "We also should probably look at crystallizing the proteins from some of these genes, which can tell us more about what they interact with."

There may be human diseases where these genes are mutated or missing, Stahl speculates. The effects of such conditions could provide important clues to what the humans-only genes do.

"It's also going to be very interesting for evolutionary biologists to try to develop a sense for where these humans-only genes come from," Stahl says. "The building blocks of these genes may be present but not active in earlier species."


'/>"/>

Contact: Michael Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

Related biology news :

1. Unmanned aerial vehicles mark robotic first for British Antarctic Survey
2. Surprising discovery from first large-scale analysis of biodiversity and biogeography of viruses
3. The Lancet publishes first clinical trial data of a fully bioabsorbable drug eluting stent
4. NHLBI issues first US von Willebrand Disease clinical practice guidelines
5. Iowa State researchers help piece together the corn genomes first draft
6. First wind turbines on Galapagos Islands will halve diesel imports, reduce risk of future oil spills
7. Map is first to track global human influences on ocean ecosystems
8. First map of threats to marine ecosystems shows all the worlds oceans are affected
9. First datasets for national biomass and carbon dataset now available
10. Stanford researchers make first direct observation of 3-D molecule folding in real time
11. Genes and environment interact in first graders to predict physical but not social aggression
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/3/2016)... , May 3, 2016  Neurotechnology, a provider ... MegaMatcher Automated Biometric Identification System (ABIS) , ... multi-biometric projects. MegaMatcher ABIS can process multiple complex ... any combination of fingerprint, face or iris biometrics. ... SDK and MegaMatcher Accelerator , which ...
(Date:4/19/2016)... DUBAI , UAE, April 20, 2016 ... can be implemented as a compact web-based "all-in-one" system ... in the biometric fingerprint reader or the door interface ... requirements of modern access control systems. The minimal dimensions ... the ID readers into the building installations offer considerable ...
(Date:3/31/2016)... 31, 2016   ... the "Company") LegacyXChange is excited to release ... soon to be launched online site for trading 100% ... ) will also provide potential shareholders a sense of ... to an industry that is notorious for fraud. The ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016 Houston Methodist Willowbrook Hospital ... Sports Association to serve as their official health ... Methodist Willowbrook will provide sponsorship support, athletic training ... association coaches, volunteers, athletes and families. ... Sports Association and to bring Houston Methodist quality ...
(Date:6/23/2016)... -- The Biodesign Challenge (BDC), a university competition that asks ... systems and biotechnology, announced its winning teams at the ... York City . The teams, chosen ... MoMA,s Celeste Bartos Theater during the daylong summit. Keynote ... of architecture and design, and Suzanne Lee , ...
(Date:6/23/2016)... ... ... STACS DNA Inc., the sample tracking software company, today announced that Dr. Hays ... DNA as a Field Application Specialist. , “I am thrilled that Dr. Young ... DNA. “In further expanding our capacity as a scientific integrator, Hays brings a wealth ...
(Date:6/23/2016)... Calif. , June 23, 2016  Blueprint Bio, ... biological discoveries to the medical community, has closed its ... Matthew Nunez . "We have received ... with the capital we need to meet our current ... essentially provide us the runway to complete validation on ...
Breaking Biology Technology: