|
Andreas Ziegler
Humboldt-Universität zu Berlin,
Germany
Title
MHC, olfactory receptor genes, and
mate selection
Abstract
Polymorphic genes of the major histocompatibility
complex (MHC) and olfactory receptors (OR) have repeatedly been implicated in
various aspects of mate choice and reproductive performance. It is widely
believed that olfaction-driven mate choice serves the purpose of securing MHC
heterozygosity in the offspring, since such
individuals should have an advantage in dealing with infections. MHC
non-identical mating partners will consider each other more attractive in
olfactory terms than MHC-similar partners. In analogy to mechanisms operating
in plants and invertebrates, selective forces aimed at securing an optimal
reproductive success could also operate within female vertebrates during and
after fertilization ("cryptic female choice"). Together with
MHC-encoded molecules, the products of human MHC (HLA)-linked OR genes could
principally be involved, not only by participating in olfaction-influenced
mate choice, but also by guiding spermatozoa towards the oocyte.
Testicular expression of polymorphic HLA class I heavy chains and OR could
indicate that these proteins might be functionally connected and involved in
a selection process which results in the expression by spermatozoa only of
such OR that are unable to interact with male self-proteins, in particular
self-MHC antigens. Consequently, polymorphic non-self proteins, e.g.
different MHC molecules provided by the female, might be involved in
attracting certain spermatozoa by interacting with specific OR. This form of
cryptic female choice could act already before the actual encouter
of oocyte and spermatozoon, via the establishment
of gradients of soluble female MHC molecules along the fallopian tube. Only
those spermatozoa would be encouraged to swim towards the oocyte
that carry OR recognizing female MHC antigens. Together with further
selection processes operating at the level of the fertilized oocyte, the chances for the formation of a zygote
exhibiting MHC homozygosity might be reduced, and a
costly investment by the female into an embryo with potentially suboptimal
genetic and immunological properties be avoided.
Biography
Prof. Andreas Ziegler studied biology at the Technische
Hochschule Darmstadt, and genetics and biochemistry
at the University
of Heidelberg.
He was trained at the Max-Planck-Institut für Medizinische Forschung, Heidelberg (Diploma thesis, Prof. S.C.
Harrison, Dr. R. Leberman), the Basel Institute for
Immunology (Doctoral thesis, Dr. J.R.L. Pink) and the MRC Laboratory of
Molecular Biology, Camvridge, UK (Postdoctoral
Fellowship of the Royal Academy, Dr. C. Milstein). Following work at the
Universities of Tübingen and Marburg,
he became Director of the Institute for Immunogenetics
(Charité - Universitätsmedizin
Berlin, Humboldt-University Berlin).
He is interested in selection processes within the human immune and
reproductive systems and in structure/function relationships of membrane
molecules.
Selected
publications (1997-2004) on MHC-linked olfactory receptor genes and topics
related to MHC genetics, including reproductive performance
- Ziegler,
A. Biology of chromosome 6. DNA Sequence 8, 189-202 (1997)
- Malfroy, L., Roth, M., Borot, N., Carrington, M., Volz,
A., Ziegler, A., and Coppin, H.
Heterogeneity in rates of recombination in the 6 Mb region telomeric to the human major histocompatibility
complex. Genomics 43, 226-231
(1997)
- Ziegler,
A. and Volz, A. Geruchsbeeinflußte
Partnerwahl, MHC und Fertilität. Bioforum 21, 284-291 (1998)
- Ziegler,
A., Ehlers, A., Forbes, S., Trowsdale, J., Uchanska-Ziegler, B., Volz,
A., Younger, R., and Beck, S. Polymorphic olfactory receptor genes and
HLA loci constitute extended haplotypes. In Major Histocompatibility
Complex – Evolution, Structure, and Function (Kasahara,
M., ed.), Springer Verlag, Tokyo, pp. 110-130 (2000)
- Ziegler,
A., Ehlers, A.,
Forbes, S., Trowsdale, J., Volz,
A., Younger, R., and Beck, S.
Polymorphisms in olfactory receptor genes: A cautionary note. Hum. Immunol. 61,
1281-1284 (2000)
- Ehlers, A., Beck, S., Forbes, S., Trowsdale, J., Volz, A.,
Younger, R., and Ziegler, A. MHC-linked olfactory
receptor loci exhibit polymorphism and contribute to extended HLA/OR haplotypes. Genome Res. 10, 1968-1978 (2000)
- Younger,
R.M., Amadou, C., Bethel, G., Ehlers, A., Fischer-Lindahl, K., Forbes, S., Horton, R., Milne, S., Mungall, A.J., Trowsdale,
J., Volz, A., Ziegler, A., and Beck, S. Characterisation of clustered MHC-linked olfactory
receptor genes in human and mouse. Genome Res. 11, 519-530 (2001)
- Ziegler,
A., Dohr, G., and Uchanska-Ziegler,
B. Possible roles for products of polymorphic MHC and linked olfactory receptor genes
during selection processes in reproduction. Am. J. Reprod.
Immunol. 48,
34-42 (2002)
- Volz, A., Ehlers, A., Younger,
R.M., Forbes, S., Trowsdale, J., Schnorr, D., Beck, S., and Ziegler, A. Complex
transcription and splicing of odorant receptor genes. J. Biol. Chem. 278, 19691-19701 (2003)
- Amadou, C., Younger, R.M., Sims,
S., Matthews, L.H., Rogers,
J., Kumánovics, A., Ziegler, A., Beck, S., and
Fischer Lindahl, K. Co-duplication of
olfactory receptor and MHC class I genes in the mouse major histocompatibility complex. Hum. Molec.
Genet. 12, 3025-3040 (2003)
- Ziegler,
A. Moleküle des MHC und olfaktorische
Rezeptoren: Mögliche Bedeutung im Rahmen der Reproduktion. J. Fertil. Reprod.
13, 14-18 (2003)
- Ziegler,
A., Dohr, G., Kentenich,
H., and Uchanska-Ziegler, B. Self – nonself discrimination and reproductive performance.
In HLA 2004. Immunobiology
of the Human MHC. Proceedings of the 13th International Histocompatibility Workshop and Congress (Hansen,
J.A. and Dupont, B., eds.), IHWG Press,
Seattle, in press (2004)
- Ziegler,
A., Beck, S., Ehlers, A., Younger, R., and Volz,
A. Testicular transcripts of HLA-linked olfactory receptor genes exhibit
unorthodox features. In HLA 2004. Immunobiology of the Human MHC. Proceedings of
the 13th International Histocompatibility
Workshop and Congress (Hansen, J.A. and Dupont,
B., eds.), IHWG Press, Seattle, in press (2004)
- Horton,
R., Wilming, L., Rand, V., Lovering,
R.C., Bruford, E.A., Khodiyar,
V.K., Lush, M.J., Povey, S., Talbot, C.C.,
Wright, M.W., Wain, H.M..
Trowsdale, J., Ziegler, A., and Beck, S. Gene
map of the extended human major histocompatibility
complex. Nat. Rev. Genet., in press (2004)
Selected
publications (1999-2004) on structural biology of HLA antigens
- Menßen, R., Orth,
P., Ziegler, A., and Saenger, W. Decamer-like conformation of a nona-peptide
bound to HLA-B*3501 due to nonstandard
positioning of the C-terminus. J. Mol. Biol. 285, 645-653 (1999)
- Rehm, A., Rohr, A., Seitz, C., Wonigeit, K., Ziegler, A., and Uchanska-Ziegler,
B. Structurally diverse forms of HLA-B27 molecules are displayed in vivo in a cell type-dependent
manner. Hum. Immunol. 61, 408-418 (2000)
- Hillig, R.C., Coulie,
P. G., Stroobant, V., Saenger,
W., Ziegler, A., and Hülsmeyer, M. High
resolution structure of HLA-A*0201 in complex with a tumour-specific
antigenic peptide encoded by the MAGE-A4 gene. J. Mol. Biol. 310, 1167-1176 (2001)
- Dangoria, N.S., DeLay,
M., Kingsbury, D.J., Mear, J.P., Uchanska-Ziegler, B., Ziegler, A., and Colbert, R.A.
HLA-B27 misfolding is associated with aberrant
intermolecular disulfide bond formation (dimerization)
in the endoplasmic reticulum. J. Biol. Chem. 277, 23459-23468 (2002)
- Hülsmeyer, M., Hillig,
R.C., Volz, A., Rühl,
M., Schröder, W., Saenger,
W., Ziegler, A., and Uchanska-Ziegler, B.
HLA-B27 subtypes differentially associated with disease exhibit subtle
structural alterations. J. Biol. Chem. 277, 47844-47853 (2002)
- Uchanska-Ziegler, B. and Ziegler,A. Ankylosing spondylitis: a 2m-deposition
disease?
Trends Immunol. 24, 73-76 (2003)
- Hillig, R.C., Hülsmeyer,
M., Welfle, K., Misselwitz,
R., Welfle, H., Saenger,
W., Kozerski, C., Volz,
A., Uchanska-Ziegler, B., and Ziegler, A.
Thermodynamic and structural analysis of peptide- and allele-dependent
properties of two HLA-B27 subtypes exhibiting differential disease
association. J. Biol. Chem. 279,
652-663 (2004)
- Hülsmeyer, M., Fiorillo,
M.T., Bettosini, F., Sorrentino,
R., Saenger, W., Ziegler, A., and Uchanska-Ziegler, B. Dual, HLA-B27 subtype-dependent
conformation of a self-peptide.
J. Exp. Med. 199, 271-281
(2004)
- Pöhlmann, T., Böckmann,
R.A., Grubmüller, H., Uchanska-Ziegler, B., Ziegler, A., and Alexiev, U. Differential peptide dynamics is linked
to MHC polymorphism. J. Biol. Chem. 279,
28197-28201 (2004)
- Uchanska-Ziegler, B., Alexiev, U., Hillig, R., Hülsmeyer, M., Pöhlmann,
T., Saenger, W., Volz,
A., and Ziegler, A. X-ray crystallography and dynamic studies of
HLA-B*2705 and B*2709 molecules complexed with
the same peptide. In HLA 2004. Immunobiology of the Human
MHC. Proceedings of the 13th International Histocompatibility Workshop and Congress (Hansen,
J.A. and Dupont, B., eds.), IHWG Press,
Seattle, in press (2004)
|
