Researchers identify candidate human pheromone receptor gene (circa 2001)

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    Oct 2002

    Researchers identify candidate human pheromone receptor gene (circa 2001)

    Quote Originally Posted by Rockefeller University
    Original here

    A team of researchers from The Rockefeller University in New York and the Yale University School of Medicine has identified for the first time a candidate pheromone receptor gene in humans. The findings, reported in the September issue of Nature Genetics, may shed new light on the molecular basis of social communication between humans.

    "We have shown that contrary to the prevailing notion in the field, the human genome contains at least one gene that encodes a candidate pheromone receptor," says Peter Mombaerts, M.D., Ph.D., assistant professor and head of the Laboratory of Developmental Biology and Neurogenetics at Rockefeller. Mombaerts led the research team, which included first author Ivan Rodriguez, Ph.D., and Mai Y. Mok, from the Laboratory of Developmental Biology and Neurogenetics at Rockefeller, and Charles A. Greer, Ph.D., professor of Neuroscience at Yale.

    The gene, called V1RL1 (V1R-like gene-1), encodes a protein that shares amino acid similarity with the mouse and rat pheromone receptors.

    Pheromones are essential chemicals used by individuals of the same species to communicate with each other, eliciting specific behaviors. In mammals, these chemical signals are detected in the nasal cavity by sensory neurons that express pheromone receptors. In rodents, these receptors belong to two large multigene families, called V1r and V2r. Although pheromonal effects have been demonstrated in humans - most notably the synchronization of the menstrual cycles of women living in close proximity - no human counterparts to the rodent pheromone receptor genes have been previously reported.

    The researchers took a genomics approach and found eight different human sequences that resemble rodent V1r sequences. Seven of the sequences were determined to be "pseudogenes." A pseudogene looks like a gene, but is defective because it does not result in the production of an intact protein.

    "Pseudogenes are typically an evolutionary vestige," says Mombaerts. "To other species, such as rodents, those genes may have been important for survival, but to us, they have become defective because there is no selective pressure to keep them intact."

    "In mice, we think there are more than 100 functional genes in the V1r family," says Rodriguez, "but in humans, V1RL1 may very well be the sole functional V1r counterpart."

    The researchers screened a wide range of human tissues to determine where V1RL1 gene expression takes place. They found expression consistently in the olfactory mucosa, which is used to detect smells, but not in most other tissues. Expression was detected in brain, lung and kidney, but not reproducibly, suggesting low expression levels in these organs, which may not be functionally significant.

    The team looked at 11 individuals of varying ethnicities and found two forms of the V1RL1 receptor that differ by only two amino acids.

    "In none of these people was V1RL1 a pseudogene, suggesting that evolutionary selection has maintained it in a functional state throughout the human species," says Rodriguez.

    In rodents, pheromone detection is thought to occur mainly via the vomeronasal organ (VNO), a specialized sensory organ located at the base of the nasal septum. Surgical removal of the VNO has a dramatic effect on the social and reproductive behavior of rodents, particularly when performed at a very young age. The "V" of "V1r genes" refers to the expression of these genes in neurons of the rodent VNO.

    "The nose of the newborn human harbors a cigar-like structure resembling a rodent VNO, but it regresses with time," says Greer. "A vestigial VNO is still left in some adult human beings, but little evidence exists that it is functional. We have been able to circumvent this anatomical conundrum by taking a novel approach strictly based on genomics."

    Why is V1RL1 still present and functional in the human genome? The scientists do not know yet. "Our discovery could lead to novel products for consumers and patients," speculates Mombaerts.

    The research was supported in part by the U.S. National Institutes of Health, the March of Dimes Birth Defects Foundation and Senomyx, Inc., a San Diego biotechnology company. Rodriguez was supported by postdoctoral fellowships from the Swiss National Science Foundation, the European Molecular Biology Organization and the Human Frontier Science Program.

    Rockefeller began in 1901 as The Rockefeller Institute for Medical Research, the first U.S. biomedical research center. Rockefeller faculty members have made significant achievements, including the discovery that DNA is the carrier of genetic information and the recent determination of the 3-D structure of the cellular RNA polymerase, a molecular machine that activates individual genes. The university has ties to 20 Nobel laureates, including the recipient of the 1999 Nobel Prize for Physiology or Medicine, Günter Blobel. Thirty-two faculty members are elected members of the U.S. National Academy of Sciences, including the president, Arnold J. Levine, Ph.D.
    Time to start posting threads about pheromones!

    Let's see who can flex their search skills and get some articles. This is a game of who has the better article...some for the notion of pheromones and others against.

    I'll open the exchange with this simple news article from a few years back. Next, we'll take it to the next level with more technical articles. You bros know how we do it...


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    Oct 2002

    Quote Originally Posted by Genome News Network
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    Somehow, the notion that humans don't have any pheromone receptor genes came to be conventional wisdom in the scientific community. And that notion may turn out to be true. But this week a team of researchers announces that the human genome contains at least one gene that closely resembles a family of mouse pheromone receptors—genes that are primarily involved in detecting odorless chemicals such as pheromones. These chemicals are the signals of a 'second' olfactory system in many species: the release of pheromones by one individual, for example, can trigger sexual behavior in another individual. The proposed human pheromone receptor is expressed in the main system of smell in humans, according to the researchers.


    If the gene really was a pheromone receptor, what is it doing now?

    "We took a molecular approach and asked whether any aspects of a pheromonal system are preserved in the human genome," says Peter Mombaerts, of The Rockefeller University in New York. Two years ago, his laboratory identified eight human DNA sequences that share distinct structural elements with mouse pheromone receptors. Seven of the sequences proved not to be functional genes. One sequence, however, encodes a receptor protein found in epithelial tissue in the nasal cavity. The findings appear in the September issue of Nature Genetics.

    For decades, studies have found physiological evidence of pheromonal effects in humans, most notably the synchronization of menstrual cycles of some women who live together. In 1995, the discovery of pheromone receptor genes in the mouse sparked new interest in these genes in humans. No one has been able to demonstrate that humans have an accessory, or vomeronasal, olfactory system. The organ that mediates 'unconscious' chemical communication in mice is essentially a vestigial shell in adult humans. The structure, the vomeronasal organ, or VNO, was first described in 1813 by the Dutch anatomist Ludvig Jacobson and is commonly referred to as Jacobson's organ.

    Turning to the genome for evidence

    The fact that the VNO is vestigial in adulthood doesn't preclude the survival of vomeronasal receptor genes. Convinced that the conventional wisdom about these genes was not based on any hard evidence, Mombaerts began searching the human genome for evidence of an accessory system of smell. In the mouse, vomeronasal receptors are structurally distinct from odorant receptors in the main olfactory system, suggesting that human counterparts would be recognizable. By 1998, it was clear that mice have more than 100 vomeronasal receptor genes, comprising two gene families, V1r and V2r.

    When the search began, a relatively small amount of human sequence data was available. The researchers used the mouse data and a combination of traditional gene-hunting techniques to find the eight human sequences. The proposed gene, which is called V1RL1 (V1r-like gene-1), resides on chromosome 19. The gene has been present in public databases for some time, and Mombaerts admits that his group initially did not recognize the sequence as a receptor candidate.

    With the sequence in hand, the researchers analyzed DNA from an ethnically diverse group of 11 individuals and found two forms of the V1RL1 gene, each with a slightly different structure. Mombaerts doesn't rule out the possibility that more pheromone receptors will turn up in sequence data in the future, but he is confident that only a few more, if any, will emerge.

    Expression studies

    To determine where in humans the V1RL1 gene is expressed, Mombaerts teamed up with Charles Greer, who directs the Neurosurgery Research Laboratories at Yale University. The researchers screened a variety of human tissues and detected low levels of activity in the brain, lung and kidney. That activity, says Mombaerts, was not unexpected and is probably insignificant. More important, he consistently found expression of V1RL1 in the olfactory mucosa, which is involved in scent detection. The specific types of human cells that express the gene have not been identified, in part because of the technical challenges involved.

    If V1RL1 really is a vomeronasal receptor, how did it end up in the main olfactory system? The question cannot be answered, of course, but natural selection may be to blame. "Genes survive or they don't survive," says Greer. "One possible explanation is that this receptor is better at detecting chemicals than was a gene in the olfactory epithelium."

    "Until this report," Greer continues, "the consensus was that humans do not have receptors that belong to this family of genes. Now the door is open to reconsidering the functional organization of the human olfactory system." Studies in pigs and rabbits have found that the two olfactory systems are probably not completely separate entities. Pigs that lack a functional VNO can detect pheromones through the main olfactory system, for example.

    An ‘Autobahn’ of possibilities

    "This is a pivotal study," says Charles Wysocki, of the Monell Chemical Senses Center and the University of Pennsylvania. "The new avenues it opens are like an Autobahn: People will ask questions that would not have been asked otherwise, and these are questions that people can actually do something about." He notes that studies are underway to characterize the VNO and accessory olfactory systems in great apes.

    Wysocki wants to know if this gene is present in the main system and/or the accessory system of a variety of mammals, especially animals like dogs and horses. If V1RL1 is present only in the accessory system of animals that have both systems, then one might conclude that the gene somehow migrated to the main system in humans, he says. It would suggest that V1RL1 "is probably very important and is finding a way to get expressed."

    The Nature Genetics paper doesn't address the question of whether humans have a vomeronasal system, which is where one would expect to find this gene, notes Wysocki. He also disagrees with Mombaerts' use of the term 'pheromone receptor' because it implies that more is known about pheromones and the vomeronasal and main olfactory systems than actually is. "Animals can respond to pheromones using the main olfactory system," he says, "so to make an equivalency between the VNO and pheromones is a false equivalency."
    Another article from the Genome News Network...


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