Mating
types in yeast, vomeronasal organ in rodents, homosexuality
in humans: Does a guiding thread exist?
by
Daniele Oliva
Dr. Daniele Oliva, Ph.D. via Annibale 52 90149 Palermo, Italy
TEL: +39 333 209 7533 E-MAIL: oliva12@libero.it
Keywords:
mating types; pheromones; pheromone receptors; vomeronasal
organ; homosexuality
Abstract
Pheromones and their receptors are the molecules used by very
different organisms in order to join two haploid cells. It
happens evidently in yeast, since the two blending haploid
cells are also the two mating organisms, whereas in rodents
pheromone receptors are the triggers of the vomeronasal system
which, supervising sexual behaviors, is responsible for copulation
and therefore for fertilization. The debate is still open
about the real significance of pheromones in humans but a
working vomeronasal organ, able to recognize pheromones of
the same sex, could be the simplest biological explanation
of homosexuality. This hypothesis is discussed and connected
with some well known experimental data.
Evolutionistic
advantages of sexual reproduction are well known: the fusion
of two haploid cells, arisen by meiosis, generating one diploid
zygote, allows the creation of individuals with always different
genomic inheritance, high genetic variability in the population
and better possibilities of adaptation to the environment.
Indeed a simple unicellular organism, the yeast Saccharomyces
cerevisiae, presents haploid cells of two different "mating
types" (sexes), a and a [1].
Cells of different mating types are able to recognize each other,
by production of specific polypeptide pheromones and their bond
to superficial receptors, proteins belonging to the family of
GPCRs (G protein-coupled receptors), provided with seven hydrophobic
domains crossing the cellular membrane [2]: when receptors bound
the pheromones produced from the opposite mating type, they
induce a cascade of cellular reactions leading to the fusion
of the two cells a and a and to the creation of a diploid organism
[3]. In case of much more complicated organisms, as mammals,
the fusion of two haploid cells, egg and sperm, bears the same
result.
It looks that well functioning mechanisms are well preserved.
In fact animals reproducing by internal fertilization have to
recognize each other before mating and it is well demonstrated,
at least in rodents, that sexual behaviors are controlled by
the vomeronasal system [4,5]: through the accessory olfactory
bulb, the medial preoptic area and the medial amygdala, some
hypothalamic nuclei are connected to the vomeronasal organ,
a sensory pit situated on both sides of the nasal septum and
able to recognize pheromones produced by individuals of the
opposite sex [6]. Both vomeronasal organ and system are sexually
dimorphic [7]. What has that got to do with yeast? Also in rodents
pheromone receptors are proteins with seven hydrophobic domains
crossing the membrane of sensorial cells [8]. This time the
immediate consequence of the bonding between pheromone and receptor
is a single nervous impulse toward the hypothalamus, but the
final result will be always the same: the fusion of two haploid
cells to form one diploid cell. Anyhow the trigger, releasing
the whole chain of events ending with the fertilization, utilizes
the same molecules already used in yeast: the pheromone receptors.
If probably most of us have no difficulty to see this guiding
thread flowing trough all eucaryotic evolution, till rodents,
it is not as simple when we are directly involved as human beings.
Since 1991, with the discovery that the vomeronasal organ is
present and working also in humans [9-12], a debate has arisen
in the scientific community about the real role of pheromones
in human sexual behaviors, but after more than a decade, there
are not clear and final answers in the affirmative or negative:
sometimes the vomeronasal organ is almost always present [11],
sometimes this is not really true [13]; for some researchers
it is working [12], but for others there is no connection to
the higher nerve centers [14]. I never had the chance of studying
experimentally the problem, but in my opinion it seems very
difficult that a mechanism, so well preserved since the dawning
of the sexual reproduction, was lost in the short lapse of time,
and of genes, that separate us from rodents.
Yet it exists a simple way for having new information about
the putative role of the vomeronasal organ in human sexual behavior,
but I didn't find any notice about it, also in recent literature
[15,16]: in 1991 the use of an apparatus was reported, able
to measure the electric potential of the human vomeronasal organ
in consequence of pheromone supply [12]. Why don't do the same
experiment using a large sample of homosexual men and women?
Of course many people will answer that the human sexual orientation
depends on manifold factors, as social, cultural and religious,
but I think that Homo sapiens belongs always to the class of
mammals and, if the vomeronasal organ is actually involved in
human sexual behavior, a meaningful number of homosexuals will
be able to recognize the pheromone produced by the same sex,
but not that produced by the opposite. What's more, the measure
will be expressed not using an arbitrary pleasantness scale,
but in millivolts.
A recent research demonstrates that male mice with a homozygous
deficiency in a receptor of the vomeronasal organ mount both
females and other males [17]. Besides a linkage between vomeronasal
organ and homosexuality in humans could explain the meaning
of many experimental data. For instance the small (i.e. feminine)
dimension of the third interstitial nucleus of the anterior
hypothalamus of homosexual men [18]: it could be one of the
nuclei of the vomeronasal system, which in rodents is sexually
dimorphic. Also the association of markers on X chromosome and
the male homosexual orientation [19]: perhaps loci of regulatory
or structural genes of the vomeronasal system? Also that the
sex hormone levels which the fetus is subjected to are important
for the future sexual orientation of the adult [20]: the genes
of man and woman are essentially the same; then it is acceptable
that every individual has the genes needed for forming both
a "masculine" and a "feminine" vomeronasal
system: the choice between one or the other could be controlled
by the hormonal levels in the prenatal period. Besides the idea
is not new that an individual can have the genes for both "mating
types" and expresses just one of them: it's just what happens
in yeast.
REFERENCES
1 Kurjan J. Pheromone response in yeast. Annu Rev Biochem 1992;
61:1097-1129.
2 Nakayama N, Miyajima A, Arai K. Nucleotide sequences of STE2
and STE3, cell type-specific sterile genes from Saccharomyces
cerevisiae. EMBO J 1985; 4:2643-2648.
3 Elion EA. Pheromone response, mating and cell biology. Curr
Opin Microbiol 2000; 3:573-581.
4 Halpern M. The organization and function of the vomeronasal
system. Ann Rev Neurosci 1987; 10:325-362.
5 Keverne EB. Pheromones, vomeronasal function, and gender-specific
behavior. Cell 2002; 108:735-738.
6 Brennan PA. The vomeronasal system. Cell Mol Life Sci 2001;
58:546-555.
7 Segovia S, Guillamón A. Sexual dimorphism in the vomeronasal
pathway and sex differences in reproductive behaviors. Brain
Res Brain Res Rev 1993; 18:51-74.
8 Mombaerts P. Seven-transmembrane proteins as odorant and chemosensory
receptors. Science 1999; 286:707-711.
9 Moran DT, Jafek BW, Rowley JCIII. The vomeronasal (Jacobson's)
organ in man: ultrastructure and frequency of occurence. J Steroid
Biochem Molec Biol 1991; 39:545-552.
10 Stensaas LJ, Lavker RM, Monti-Bloch L, Grosser BI, Berliner
DL. Ultrastructure of the human vomeronasal organ. J Steroid
Biochem Molec Biol 1991; 39:553-560.
11 Garcia-Velasco J, Mondragon M. The incidence of the vomeronasal
organ in 1000 human subjects and its possible clinical significance.
J Steroid Biochem Molec Biol 1991; 39:561-563.
12 Monti-Bloch L, Grosser BI. Effect of putative pheromones
on the electrical activity of the human vomeronasal organ and
olfactory epithelium. J Steroid Biochem Molec Biol 1991; 39:573-582.
13 Knecht M, Kuhnau D, Huttenbrink KB, Witt M, Hummel T. Frequency
and localization of the putative vomeronasal organ in humans
in relation to age and gender. Laryngoscope 2001; 111:448-452.
14 Trotier D, Eloit C, Wassef M, Talmain G, Bensimon JL, Doving
KB, et al. The vomeronasal cavity in adult humans. Chem Senses
2000; 25:369-380.
15 Kohl JV, Atzmueller M, Fink B, Grammer K. Human pheromones:
integrating neuroendocrinology and ethology. Neuroendocrinol
Lett 2001; 22:309-321.
16 Muscarella F, Fink B, Grammer K, Kirk-Smith M. Homosexual
orientation in males: evolutionary and ethological aspects.
Neuroendocrinol Lett 2001; 22:393-400.
17 Leypold BG, Yu CR, Leinders-Zufall T, Kim MM, Zufall F, Axel
R. Altered sexual and social behaviors in trp2 mutant mice.
Proc Natl Acad Sci USA 2002; 99:6376-6381.
18 LeVay S. A difference in hypothalamic structure between heterosexual
and homosexual men. Science 1991; 253:1034-1037.
19 Hamer DH, Hu S, Magnuson VL, Hu N, Pattatucci AML. A linkage
between DNA markers on the X chromosome and male sexual orientation.
Science 1993; 261:321-327.
20 Dörner G, Götz F, Rohde W, Plagemann A, Lindner
R, Peters H, et al. Genetic and epigenetic effects on sexual
brain organization mediated by sex hormones. Neuroendocrinol
Lett 2001; 22:403-409.
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