The Chemosensory Recognition of Genetic Individuality

1. The Chemosensory Recognition of Genetic Individuality Beauchamp, Yamazaki and Boyse

2. Odor and Genes • The individual odor of an animal is in part determined by its genes • Genes in a chromosomal region in all mammals plays a major part in immunologic recognition • Largely decides the fate of transplanted organs and tissues • MHC = Major Histocompatibility Complex • Mice = H2 • Dogs = DLA • Humans = HLA

3. Olfactory Recognition of Genetic Identity • H-2k and H-2d • k and d stand for the alleles • Alleles = alternative forms of these genes • Places in the genome where mutations occur with remarkable frequency • Two unrelated individual animals are extremely unlikely to have identical MHC types • Why it is difficult to find MHC-matched human organ donors and recipients, except within families • The proteins synthesized by cells of different individuals from instructions encoded by MHC genes are also diverse

4. Olfactory Recognition of Genetic Identity • Proteins products have carbohydrate chemical groups added = glycoproteins • Inserted into the outer membrane to form surface antigens

5. Mice Breeding • Inbred Strains • Derived by serial brother-to-sister matings over many generations • To the point of genetic uniformity • Congenic Strains • Derived by first crossing one inbred strain to another • Mate the progeny through many succeeding generations back to mice of the first inbred strain • Then select progeny in each backcross generation for a defined genetic difference • The result is two strains of mice that differ in only one segment of the genetic material • For MHC the congenic strains would be genetically identical except for the region of chromosome 17 that bears the MHC (H-2) group of genes

6. Congenic Mice Receiver Donor

7. Filial Generations • The parental generation is the first set of parents crossed. • The F1 (first filial) generation consists of all the offspring from the parents - their children. • The F2 (second filial) generation consists of the offspring from allowing the F1 individuals to interbreed - the grandchildren of the parental generation.

8. F2 Linkage Test • A pair of H-2 congenic strains (genetically identical except for H-2) is crossed to produce the F1 generation • F1 – first filial (children) • The F1 population consists of genetically uniform mice that are H-2 heterozygotes • Every F1 mouse carries both the paternal and maternal H-2 alleles • The F1 H-2 heterozygotes are then crossed to give the F2 generation (grandchildren) • The F2 consists of two groups of H-2 homozygotes, each genetically identical with the respective inbred grandparent strain

10. Mating Preferences • Although the F2 homozygotes are genetically identical with the respective grandparents, they have experienced a different environment with respect to H-2 • The H-2 mating preferences of F2 homozygotes were not in all cases identical with the preferences of genetically identical mice of the grandparental strains • The MHC-related mating preferences of mice are at least in part the result of familiar chemosensory imprinting

11. Basis of Mating Preferences • Mice can sense one another’s H2 types • Favoring partners that differ from themselves at the H2 locus • This bias favors outbreeding and H2 heterozygosity • Promotes diversity of H2 genes • May help the immune system adapt to new threats

12. Odor • It is well to remember that readily distinguishable compound odors can be generated simply by varying the proportions of the chemical constituents of a given mixture of odorants • Variations in the output of odorous metabolites arising from MHC genetic variation might alone account for individual odors related to MHC types