CptKipling
02-11-2005, 12:02 PM
http://www.genomenewsnetwork.org/artic
les/08_00/human_pheromone.shtml (http://www.genomenewsnetwork.org/articles/08_00/human_pheromone.shtml) (article below in case it disappears in a few months)
Proposed human
pheromone receptor is expressed in olfactory tissue
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.
"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."
les/08_00/human_pheromone.shtml (http://www.genomenewsnetwork.org/articles/08_00/human_pheromone.shtml) (article below in case it disappears in a few months)
Proposed human
pheromone receptor is expressed in olfactory tissue
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.
"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."