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Compatibility Systems in Nature
M.Tevfik Dorak, MD, PhD
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Self and non-self recognition is a common requirement for all living organisms. Most taxa have their own systems to identify self and non-self. Nature makes use of these systems for several purposes. One common use is to avoid inbreeding by identifying individuals, cells or gametes as different from self (self-incompatibility as in mate choice, selective fertilization). Also in adults, the same discrimination finds its use in co-operation between individuals or cells (self-compatibility as in kin recognition, colony formation, nuclear fusion, dual recognition, transplantation). It is not infrequent that the same system is involved in both levels of recognition in the same species.
Bacteria, protoctista, fungi and plants have well studied compatibility systems. In the animal kingdom, invertebrates have an allorecognition system which is primarily involved in immunological recognition but also in fertilization. The other major division in the animal kingdom, the vertebrates, invariably has the Major Histocompatibility System (MHC). Recent evidence suggests that inbreeding avoidance is one of the less appreciated functions of the MHC. Here, a review of the compatibility systems in nature will be followed by the involvement of the MHC in reproductive phenomena. The similarities between the MHC and other compatibility systems will be emphasized with the view that the MHC is primarily an inbreeding avoidance system and its role in histocompatibility is a secondary one 1.
The best known compatibility systems are the protozoan pheromone system 2; 3, the fungal (in)compatibility systems 4-8, angiosperm (flowering plants) self-incompatibility system 6; 9; 10, and the invertebrate allorecognition systems 11-14. All of these systems are primarily involved in prevention of matings between genetically similar individuals to avoid the harmful effects of inbreeding. As a result of the most polymorphic compatibility system, the fungus Schizophyllum commune (the edible mushroom) has the maximal (98.8%) rate of outbreeding in nature. Even in bacteria in which reproduction is asexual (by binary fission) as a rule, there are mechanisms to increase genetic diversity via horizontal gene transfer (conjugation) (see Microbial Genetics). The green alga Spirogyra and the Zygomycetes phylum of the fungal kingdom use the mechanism for the same purpose.
Fungal compatibility systems
The fungal incompatibility system regulates both sexual reproduction and somatic compatibility. The first major review on this subject was presented by Raper in 1966 15. More recent reviews cover the mating types and pheromone systems in Basidiomycetes and Ascomycetes 5; 8; 16-20. Between the two phyla, Basidiomycetes species may have thousands of (tetrapolar) mating types as well as a pheromone system. The somatic compatibility system which regulates self/nonself recognition during vegetative growth in filamentous fungi has also been extensively reviewed 5; 21; 22.
In fungi, both asexual and sexual reproductions are observed. In sexually reproducing fungi, there is no distinction between male and female structures but there is a genetically determined difference among individual fungi. This is due to the mating types. Individuals of the same mating type cannot mate with one another. The nuclei of most fungi are haploid except when a zygote is formed in sexual reproduction. The diploid zygotes undergo meiosis, producing haploid nuclei that will be integrated into the spores. When haploid fungal spores germinate, their nuclei divide mitotically to produce hyphae (the structural unit of a fungus in its vegetative phase or mycelium). These haploid hyphae in filamentous fungi may be in a dikaryotic stage (n+n) which is different from haploid (n) or diploid (2n) state. The co-existence of two different nuclei (heterokaryon or dikaryon) in the same cell is regulated by the somatic/vegetative/heterokaryon compatibility system. The studies on the compatibility systems in Basidiomycetes 19 include those on the smut fungus Ustilago maydis 23-26, U.hordei 8 and the edible members (mushrooms) Schizophyllum commune 7 and Coprinus cinereus 27. The members of the other phylum Ascomycetes 17; 18 studied are the unicellular yeasts Saccharomyces cerevisiae 28-30 and Schizosaccharomyces pombe 17; 19; the filamentous ascomycetes Neurospora crassa 31-34, Podospora anserina 35; 36 and Cochliobolus heterostrophus; and Aspergillus nidulans 37-39. Unique features of these groups are that Basidiomycetes have more complex mating type systems consisting of much more polymorphic mating types and a pheromone/pheromone receptor system, and (filamentous) Ascomycetes have a somatic (heterokaryon) incompatibility system in addition to the sexual mating types. The heterokaryon compatibility system (het loci) regulates the heterokaryon formation in filamentous fungi. Filamentous fungi are capable of hyphal fusion to form dikaryotic heterokaryons during their vegetative growth but the formation of this new composite mycelium is under the control of het loci as well as one of the mating type loci 5; 21; 40-42. The coexpression of the antagonistic het alleles triggers a lethal reaction and prevents the formation of viable heterokaryons. In Neurospora crassa, allelic differences at any one of at least 11 het loci trigger an incompatibility response (thus, the heterokaryon is homozygous at all het loci). The number of the het loci in other Ascomycetes is 17 in P.anserina, eight in A.nidulans and at least five in Cryphonectria parasitica (the chestnut blight ascomycete) 5; 21. The heterokaryon formation and the role of similarity in this process is very similar to the control of colony formation and fusion in invertebrates 13, kin recognition in mice 43; 44, and transplant acceptance in the animal kingdom 45-49. Heterokaryosis is the first step in sexual reproduction of non-filamentous fungi such as Basidiomycetes, but here diversity is favored and this is regulated by the mating types 19. Allelic incompatibility in the het loci does not generally affect sexual function; strains with numerous het differences can mate.
In N.crassa, which is heterothallic (self-incompatible), strains of opposite mating type, A and a, must interact to give the series of events resulting in sexual reproduction: fruiting body formation, meiosis, and the generation of dormant ascospores. While the mating type sequences must be of the opposite kind for mating to occur in the sexual cycle, two strains of opposite mating type cannot form a stable heterokaryon during vegetative growth. In haploid heterothallic species, the genome only contains one of the A or a mating type loci. The genus Neurospora also includes homothallic (self-compatible) species. Those carry a single haploid nucleus and are able to form fruiting bodies, undergo meiosis, and produce new haploid spores. One such species, N. terricola, contains one copy each of the A and the a sequences within each haploid genome 34. Homothallism in these species is not due to mating-type switching, as it is in Saccharomyces cerevisiae 32. In S.cerevisiae, the genome contains both mating type loci and switching between them is possible 8. Each haploid genome contains both the a and a genes and normally one of them is transcribed with its interaction with the mating type loci while the other one is silent. Sometimes, a new copy of the silence mating type gene is made, the other one is removed from the mating type locus and the new type is transcribed.
During (sexual) conjugation in S.cerevisiae, two cells of opposite mating type (MATa and MAT a) fuse to form a diploid zygote. Conjugation requires that each cell locates an appropriate mating partner. This is achieved by pheromones and pheromone receptors. In MAT-a cells, both production of a-pheromone and response to a-pheromone are necessary for successful 'courtship' 50. Unlike the pheromone system of Basidiomycetes, in the yeast, the pheromone system is under the control of the mating types (not independent).
The function of the mating types is obviously avoidance of inbreeding with no homozygosity allowed and consequently, heterozygote advantage. This helps to increase genetic diversity and survival chances of the species. On the other hand, the function of the heterokaryon compatibility system is not clear. While having two nuclei offers the advantages of diploidy (for example, masking recessive deleterious genes), why they have to be the same genetic type is not known. One of the hypotheses is that the horizontal transfer of cytoplasmic genetic elements is reduced between incompatible strains and this protects strains of natural populations against invasion by harmful cytoplasmic genetic elements (stable RNA, mitochondria and plasmids). The prevention of horizontal gene transfer, however, is not absolute and the het loci differ in their efficiency in this process 38; 40; 51.
Mating types in fungi:
BIPOLAR MATING TYPES:
Zygomycetes: (+) and (-)
All heterothallic ascomycetes have single-locus, two-allele mating systems:
S.cerevisiae: a (a1, a2) and a (a1, a2) [type switching is possible]
N.crassa: A (mtA-1) and a (mta-1) [idiomorphic]
U.hordei: a and b (linked)
TETRAPOLAR MATING TYPES:
U.maydis: biallelic pheromone system a (a1, a2) and multiallelic b locus (homeodomain transcription factor)
S.commune and C.cinereus: multiallelic A (transcription factor) and multiallelic B (pheromone and pheromone receptor)
Plant self-incompatibility system
Mechanisms that prevent self-pollination are of crucial importance for maintaining genetic diversity within flowering plant (angiosperm) populations. This is because the flowers often have male and female organs within close proximity on the same plant and not infrequently on the same flower. Self-incompatibility, is a genetically controlled mechanism for rejection of own pollen. For a classical treatment of this subject, the reader is referred to the monograph by de Nettancourt 52. More recent reviews have dealt with the nature, molecular and population genetics of this system 9; 10; 20; 53-57. See also Plant Genetics.
Some flowers have developed mechanical barriers for their own pollen to prevent them from reaching the female organ (pistil) in the same flower or plant. Some plants have timing differences between their male and female flowerings. The self-incompatibility systems creating a topological barrier (due to different morphologies of their flowers) are called heteromorphic self-incompatibility systems 10; 52; 53. The homomorphic self-incompatibility (SI) involves the rejection of self-pollen and was first recognized by Darwin. Over half of the flowering plants have flowers with similar shape and this type of self-incompatibility 52; 58. The homomorphic type is further classified into gametophytic and sporophytic types. In the former, pollen's own SI type is perceived by the stigma and should not match either of the plants SI alleles for successful fertilization. In the more interesting sporophytic type, the two alleles of pollen's parent are recognized by the stigma and there should be no matching combination between the two alleles of the stigma and two alleles of the plant from which the pollen has derived to avoid self-rejection. The gametophytic type is more common (found in 60 families of angiosperms) than the sporophytic type (found in six families) 10. The two types are not related and evolved independently. The gametophytic type has been studied in Papaveracea (poppies), Poaceae, Rosaceae, Scruphulariaceae, and Solaneceae (including tobacco, potato and tomato). The sporophytic type has only been studied in Brassicaceae (including cabbage and mustard, for example Arabidopsis thaliana). Despite being very common among angiosperms, the SI systems in different families have different origins, in other words, they evolved independently several times 56; 59.
Self-incompatible (heterothallic) plants necessarily produce offspring that are heterozygous at the S locus which in general, contains 30-50 alleles 53; 60. The alleles of the S locus confer genetic identity (S haplotype specificity) on the pollen and stigma of self-incompatible plants. The S locus of the sporophytic type has two genes encoding two proteins expressed on the stigma surface. These are a transmembrane S receptor protein kinase (SRK) and S locus glycoprotein (SLG) which has RNAse activity 61. It is the SRK gene product which determines the S haplotype specificity of the stigma but the SI response is stronger if SLG of the same haplotype is also expressed.57. The corresponding protein on the pollen surface has recently been identified as a member of the pollen coat protein family (SCR) 62; 63. When a self pollen reaches the stigma on the same flower or plant, a self-rejection reaction takes place. The biochemical mechanism of self-rejection involves the cytotoxic action of the RNase activity 64; 65. The end result is the prevention of pollen tube growth. In the gametophytic type, the same is achieved by a single glycoprotein with an RNAse activity 66.
Just like the fungal mating types, the plant self-incompatibility system provides an example of balancing selection in the maintenance of their alleles 22; 60; 67. It is easy to imagine how this works. Any new allele would have selective advantage since a pollen with this allele will always be accepted by the stigma until this allele reaches a remarkable frequency in the population (frequency-dependent selection). Once it has been established, the frequency will still be maintained through heterozygote advantage. Since this occurs for any new allele created as a result of mutations, balancing selection results in extreme polymorphism detected in these compatibility systems including the vertebrate MHC 8; 60; 68; 69. The resulting highly diverged alleles will also have very long evolutionary lifetimes and their existence will cover the life times of several successive species (transspecies polymorphism). The evidence suggesting this pattern of polymorphism is greater sequence similarity of alleles between species than similarities within species. This is again typical of all these compatibility systems 22; 67; 70-76. Another piece of evidence for the action of balancing selection on the self-incompatibility alleles is the clustering of non-synonymous mutations in hypervariable regions (HVRs) rather than a homogeneous distribution 67. Under a strictly neutral model, there would be no such heterogeneity in the distribution of substitution rates. The continuous stretches of non-polymorphic sequences in different alleles suggest that these segments are functionally constrained and any non-synonymous substitution in these parts would be deleterious and subject to purifying selection. These segments may still have a rate of high synonymous base substitutions. On the other hand, if new alleles are favored as in heterozygote advantage, non-synonymous substitutions will be concentrated on the segments encoding the allelic specificity (HVRs). This is exactly what happens in the fungal het loci 22, plant SI 67; 72 and vertebrate MHC alleles 77-81.
Invertebrate compatibility systems
Although the MHC multigene family is restricted to vertebrates, histocompatibility loci are also found in invertebrates where they appear to have an analogous role in the regulation of mating systems 11; 82. A histocompatibility system of immunorecognition is postulated to have originated in multicellular invertebrates probably beginning with coelenterates (corals) 45; 46; 83. The best studied invertebrate compatibility system is that of the colonial tunicates 11; 13; 14; 84; 85. The best known species in this group is Botryllus schlosseri and its compatibility system is called fusion/histocompatibility (Fu/HC) (see the link below to De Tomaso Lab). Allorecognition in Botryllus is principally controlled by this single Mendelian locus, with a large number of codominantly expressed alleles 85. The number of alleles is estimated to be 30-200 13 (see a recent review on the allorecognition systems in Botryllus by McKitrick et al, 2011; and the report on selection operating on the fester histocompatibility system in Botryllus: Nydam & De Tomaso, 2012).
The ability to discriminate between self and nonself (i.e., allorecognition), is ubiquitous among colonial metazoans. The genetics of allorecognition has also been studied in another invertebrate, the colonial cnidarian Hydractinia (Buss, 1990; Cadavid et al, 2004 & 2005). Two allorecognition loci, alr1 and alr2, have been isolated in the same chromosomal region, which is called the allorecognition complex (ARC) (Rosa et al, 2010 & Rosengarten, 2011).
Colonial tunicates are complex marine invertebrates (in fact protochordates) that undergo a variety of histocompatibility reactions in their intraspecific competition for feeding surfaces. By means of these reactions, colonies fuse with kin, extend domination over a feeding surface, while isolating unrelated conspecifics. A Botryllus colony is composed of numerous units which are embedded within the translucent-gelatinous matrix, the tunic. Each hermaphroditic member possesses male and female gonads. Following fusion with nonidentical kin sharing one or more Fu/HC allele(s), the fused pair expands both chimeric partners via an asexual budding process, further extending domination over a feeding surface. However, at some later time point an intense set of histoincompatibility reactions occurs between fused kin, resulting in the destruction of all individuals of one of the genotypes, ending the chimeric state 13.
Apart from prevention of fusion with non-kin 11; 84, the Fu/HC also affects self-fertilization by sperm-egg incompatibility. Eggs resist fertilization by sperm from the same colony represented by its Fu/HC allele. This interaction results in selective fertilization by sperm bearing a different Fu/HC allele 11; 82. This situation in hermaphroditic invertebrates is very similar to what happens in fungi and plants.
As with the other compatibility systems and the MHC, there is yet no evidence for a common ancestor for the invertebrate compatibility systems and the vertebrate MHC 13; 14. This shows that the widespread existence of these systems is not due to a common ancestor but suggests a biological requirement to have a system to promote outbreeding for different taxa. The best evidence for that is that in plants, the self-incompatibility system arose independently more than once. It appears, however, that the main function of all these systems is to enforce heterozygosity by acting at the earliest phase of sexual reproduction. There is still a possibility that the vertebrate histocompatibility genes evolved from gametic self-nonself recognition systems which prevent self-fertilization in hermaphroditic organisms 11. This idea was first put forward by the Nobel Laureate immunologists Frank Macfarlane Burnet 86.
Vertebrate MHC and compatibility
The MHC also prevents inbreeding through its influence on mate choice in mice 87; 88 and humans 89; 90; and on reproductive processes in rats 91, mice 92; 93 and humans 94; 95. The reproductive mechanisms are varied and range from selective fertilization to selective abortion. A major common feature of the compatibility systems is that they favor genetic dissimilarity between mates and the gametes (mate choice, selective fertilization); but similarity in co-operation (kin recognition, dual recognition, transplant matching) 1; 96. All these functions are based on the provision of a phenotype for the genetic identity of the individual by the MHC: either cell surface molecules or chemosensory signals. See also Non-Pathogen-Based Selection in Origin of the MHC and Its Polymorphism and Kempenaers B (2007): Mate Choice & Genetic Quality.
1. Jones JS, Partridge L: Tissue rejection: the price for sexual acceptance. Nature 304:484, 1983 (www)
2. Weiss MS, Anderson DH, Raffioni S, Bradshaw RA, Ortenzi C, Luporini P, Eisenberg D: A cooperative model for receptor recognition and cell adhesion: evidence from the molecular packing in the 1.6-A crystal structure of the pheromone Er-1 from the ciliated protozoan Euplotes raikovi. Proceedings of the National Academy of Sciences USA 92:10172, 1995
3. Vallesi A, Giuli G, Bradshaw RA, Luporini P: Autocrine mitogenic activity of pheromones produced by the protozoan ciliate Euplotes raikovi. Nature 376:522, 1995
4. Metzenberg RL: The role of similarity and difference in fungal mating. Genetics 125:457, 1990
5. Begueret J, Turcq B, Clave C: Vegetative incompatibility in filamentous fungi: het genes begin to talk. Trends in Genetics 10:441, 1994
6. Hiscock SJ, Kues U, Dickinson HG: Molecular mechanisms of self-incompatibility in flowering plants and fungi - different means to the same end. Trends in Cell Biology 6:421, 1996
7. Wendland J, Vaillancourt LJ, Hegner J, Lengeler KB, Laddison KJ, Specht CA, Raper CA, Kothe E: The mating-type locus B alpha 1 of Schizophyllum commune contains a pheromone receptor gene and putative pheromone genes. EMBO Journal 14:5271, 1995
8. Kothe E: Tetrapolar fungal mating types: sexes by the thousands. FEMS Microbiological Reviews 18:65, 1996
9. Haring V, Gray JE, McClure BA, Anderson MA, Clarke AE: Self-incompatibility: a self-recognition system in plants [Review]. Science 250:937, 1990
10. Kao TH, McCubbin AG: How flowering plants discriminate between self and non-self pollen to prevent inbreeding. Proceedings of the National Academy of Sciences USA 93:12059, 1996
11. Scofield VL, Schlumpberger JM, West LA, Weissman IL: Protochordate allorecognition is controlled by a MHC-like gene system. Nature 295:499, 1982
12. Grosberg RK: The evolution of allorecognition specificity in clonal invertebrates. Quarterly Review of Biology 63:377, 1988
13. Weissman IL, Saito Y, Rinkevich B: Allorecognition histocompatibility in a protochordate species: is the relationship to MHC somatic or structural? Immunological Reviews 113:227, 1990
14. Magor BG, De Tomaso A, Rinkevich B, Weissman IL: Allorecognition in colonial tunicates: protection against predatory cell lineages? Immunological Reviews 167:69, 1992
15. Raper JR: Genetics of Sexuality in Higher Fungi. New York, Ronald Press, 1966
16. Bolker M, Kahmann R: Sexual pheromones and mating responses in fungi. Plant Cell 5:1461, 1993
17. Kronstad JW, Staben C: Mating type in filamentous fungi. Annual Review of Genetics 31:245, 1997
18. Coppin E, Debuchy R, Arnaise S, Picard M: Mating types and sexual development in filamentous ascomycetes. Microbiology and Molecular Biology Reviews 61:411, 1997
19. Casselton LA, Olesnicky NS: Molecular genetics of mating recognition in basidiomycete fungi. Microbiology and Molecular Biology Reviews 62:55, 1998
20. Hiscock SJ, Kues U: Cellular and molecular mechanisms of sexual incompatibility in plants and fungi. International Review of Cytology 193:165, 1999
21. Glass NL, Kuldau GA: Mating type and vegetative incompatibility in filamentous ascomycetes. Annual Review of Phytopathology 30:201, 1992
22. Wu J, Saupe SJ, Glass NL: Evidence for balancing selection operating at the het-c heterokaryon incompatibility locus in a group of filamentous fungi. Proceedings of the National Academy of Sciences USA 95:12398, 1998
23. Urban M, Kahmann R, Bolker M: Identification of the pheromone response element in Ustilago maydis. Molecular & General Genetics 251:31, 1996
24. Urban M, Kahmann R, Bolker M: The biallelic a mating type locus of Ustilago maydis: remnants of an additional pheromone gene indicate evolution from a multiallelic ancestor. Molecular & General Genetics 250:414, 1996
25. Kahmann R, Romeis T, Bolker M, Kumper J: Control of mating and development in Ustilago maydis. Current Opinion in Genetics & Development 5:559, 1995
26. Gillissen B, Bergemann J, Sandmann C, Schroeer B, Bolker M, Kahmann R: A two-component regulatory system for self/non-self recognition in Ustilago maydis. Cell 68:647, 1992
27. O'Shea SF, Chaure PT, Halsall JR, Olesnicky NS, Leibbrandt A, Connerton IF, Casselton LA: A large pheromone and receptor gene complex determines multiple B mating type specificities in Coprinus cinereus. Genetics 148:1081, 1998
28. Weissman JD, Singer DS: Striking similarities between the regulatory mechanisms governing yeast mating-type genes and mammalian major histocompatibility complex genes. Molecular & Cellular Biology 11:4228, 1991
29. Naider F, Gounarides J, Xue CB, Bargiota E, Becker JM: Studies on the yeast alpha-mating factor: a model for mammalian peptide hormones. Biopolymers 32:335, 1992
30. Brizzio V, Gammie AE, Nijbroek G, Michaelis S, Rose MD: Cell fusion during yeast mating requires high levels of a-factor mating pheromone. Journal of Cell Biology 135:1727, 1996
31. Glass NL, Grotelueschen J, Metzenberg RL: Neurospora crassa A mating-type region. Proceedings of the National Academy of Sciences USA 87:4912, 1990
32. Glass NL, Vollmer SJ, Staben C, Grotelueschen J, Metzenberg RL, Yanofsky C: DNAs of the two mating-type alleles of Neurospora crassa are highly dissimilar. Science 241:570, 1988
33. Arganoza MT, Ohrnberger J, Min J, Akins RA: Suppressor mutants of Neurospora crassa that tolerate allelic differences at single or at multiple heterokaryon incompatibility loci. Genetics 137:731, 1994
34. Metzenberg RL, Glass NL: Mating type and mating strategies in Neurospora. Bioessays 12:53, 1990
35. Coustou V, Deleu C, Saupe S, Begueret J: The protein product of the het-s heterokaryon incompatibility gene of the fungus Podospora anserina behaves as a prion analog. Proceedings of the National Academy of Sciences USA 94:9773, 1997
36. Barreau C, Iskandar M, Loubradou G, Levallois V, Begueret J: The mod-A suppressor of nonallelic heterokaryon incompatibility in Podospora anserina encodes a proline-rich polypeptide involved in female organ formation. Genetics 149:915, 1998
37. Butcher AC: The relationship between sexual outcrossing and heterokaryon incompatibility in Aspergillus nidulans. Heredity (Edinburgh) 23:443, 1968
38. Coenen A, Debets F, Hoekstra R: Additive action of partial heterokaryon incompatibility (partial-het) genes in Aspergillus nidulans. Current Genetics 26:233, 1994
39. van Diepeningen AD, Debets AJ, Hoekstra RF: Heterokaryon incompatibility blocks virus transfer among natural isolates of black Aspergilli. Current Genetics 32:209, 1997
40. Debets F, Yang X, Griffiths AJ: Vegetative incompatibility in Neurospora: its effect on horizontal transfer of mitochondrial plasmids and senescence in natural populations. Current Genetics 26:113, 1994
41. Hartl DL, Dempster ER, Brown SW: Adaptive significance of vegetative incompatibility in Neurospora crassa. Genetics 81:553, 1975
42. Saupe SJ, Glass NL: Allelic specificity at the het-c heterokaryon incompatibility locus of Neurospora crassa is determined by a highly variable domain. Genetics 146:1299, 1997
43. Manning CJ, Wakeland EK, Potts WK: Communal nesting patterns in mice implicate MHC genes in kin recognition. Nature 360:581, 1992
44. Brown JL, Eklund A: Kin recognition and the major histocompatibility complex: an integrative review. American Naturalist 143:435, 1994 (link)
45. Hildemann WH, Johnson IS, Jokiel PL: Immunocompetence in the lowest metazoan phylum: transplantation immunity in sponges. Science 204:420, 1979
46. Hildemann WH, Linthicum DS, Vann DC: Immunoincompatibility reactions in corals (Coelenterata). Advances in Experimental Medicine & Biology 64:105, 1975
47. Hildemann WH: Transplantation immunity in fishes: Agnatha, Chondrichthyes and Osteichthyes. Transplantation Proceedings 2:253, 1970
48. Gorer PA: The genetic and antigenic basis of tumour transplantation. Journal of Pathology & Bacteriology 44:691, 1937
49. Snell GD: Studies in histocompatibility. Science 213:172, 1981
50. Jackson CL, Hartwell LH: Courtship in Saccharomyces cerevisiae: an early cell-cell interaction during mating. Molecular & Cellular Biology 10:2202, 1990
51. Caten CE: Vegetative incompatibility and cytoplasmic infection in fungi. Journal of General Microbiology 72:221, 1972
52. de Nettancourt D: Incompatibility in Angiosperms. Berlin, Springer-Verlag, 1977
53. Ebert PR, Anderson MA, Bernatzky R, Altschuler M, Clarke AE: Genetic polymorphism of self-incompatibility in flowering plants. Cell 56:255, 1989
54. Thompson RD, Kirch HH: The S locus of flowering plants: when self-rejection is self- interest. Trends in Genetics 8:381, 1992
55. Sims TL: Genetic regulation of self-incompatibility. Critical Reviews in Plant Sciences 12:129, 1993
56. Matton DP, Nass N, Clarke AE, Newbigin E: Self-incompatibility: How plants avoid illegitimate offspring. Proceedings of the National Academy of Sciences USA 91:1992, 1994
57. Kao TH, McCubbin AG: A social stigma. Nature 403:840, 2000
58. East EM: The distribution of self-sterility in flowering plants. Proceedings of the American Philosophical Society 82:449, 1940
59. Mau SL, Anderson MA, Heisler M, Haring V, McClure BA, Clarke AE: Molecular and evolutionary aspects of self-incompatibility in flowering plants. Symposia of the Society for Experimental Biology 45:245, 1991
60. Richman AD, Uyenoyama MK, Kohn JR: Allelic diversity and gene genealogy at the self-incompatibility locus in the Solanaceae. Science 273:1212, 1996
61. Takasaki T, Hatakeyama K, Suzuki G, Watanabe M, Isogai A, Hinata K: The S receptor kinase determines self-incompatibility in Brassica stigma. Nature 403:913, 2000
62. Schopfer CR, Nasrallah ME, Nasrallah JB: The male determinant of self-incompatibility in Brassica. Science 286:1697, 1999
63. Takayama S, Shiba H, Iwano M, et al.: The pollen determinant of self-incompatibility in brassica campestris. Proceedings of the National Academy of Sciences USA 97:1920, 2000
64. Clarke AE, Newbigin E: Molecular aspects of self-incompatibility in flowering plants. Annual Review of Genetics 27:257, 1993
65. Charlesworth D: Plant self-incompatibility. The key to specificity. Current Biology 4:545, 1994
66. McClure BA, Haring V, Ebert PR, Anderson MA, Simpson RJ, Sakiyama F, Clarke AE: Style self-incompatibility gene products of Nicotiana alata are ribonucleases. Nature 342:955, 1989
67. Clark AG, Kao TH: Excess nonsynonymous substitution of shared polymorphic sites among self-incompatibility alleles of Solanaceae. Proceedings of the National Academy of Sciences USA 88:9823, 1991
68. Alberts SC, Ober C: Genetic variability of the MHC: a review of non-pathogen-mediated selective mechanisms. Yearbook of Physical Anthropology 36:71, 1993
69. Apanius V, Penn D, Slev PR, Ruff LR, Potts WK: The nature of selection on the major histocompatibility complex. Critical Reviews in Immunology 17:179, 1997
70. Dwyer KG, Balent MA, Nasrallah JB, Nasrallah ME: DNA sequences of self-incompatibility genes from Brassica campestris and B. oleracea: polymorphism predating speciation. Plant Molecular Biology 16:481, 1991
71. Vekemans X, Slatkin M: Gene and allelic genealogies at a gametophytic self-incompatibility locus. Genetics 137:1157, 1994
72. Ioerger TR, Clark AG, Kao TH: Polymorphism at the self-incompatibility locus in Solanaceae predates speciation. Proceedings of the National Academy of Sciences USA 87:9732, 1990
73. Uyenoyama MK: A generalized least-squares estimate for the origin of sporophytic self-incompatibility. Genetics 139:975, 1995
74. Rivers BA, Bernatzky R, Robinson SJ, Jahnen-Dechent W: Molecular diversity at the self-incompatibility locus is a salient feature in natural populations of wild tomato (Lycopersicon peruvianum). Molecular & General Genetics 238:419, 1993
75. Boyes DC, Nasrallah ME, Vrebalov J, Nasrallah JB: The self-incompatibility (S) haplotypes of Brassica contain highly divergent and rearranged sequences of ancient origin. Plant Cell 9:237, 1997
76. Klein J: Origin of major histocompatibility complex polymorphism: the trans-species hypothesis. Human Immunology 19:155, 1987
77. Hughes AL, Nei M: Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335:167, 1988
78. Hedrick PW, Whittam TS, Parham P: Heterozygosity at individual amino acid sites: extremely high levels for HLA-A and -B genes. Proceedings of the National Academy of Sciences USA 88:5897, 1991
79. Hughes AL, Hughes MK, Watkins DI: Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci. Genetics 133:669, 1993
80. Hughes AL, Hughes MK: Natural selection on the peptide-binding regions of major histocompatibility complex molecules. Immunogenetics 42:233, 1995
81. Hughes AL, Yeager M: Natural selection at major histocompatibility complex loci of vertebrates. Annual Review of Genetics 32:415, 1998
82. Oka H: Colony specificity in compound Ascidians, in Yukova M (ed): Profiles of Japanese Science & Scientists, Tokyo, Kodansha, 1970, p 195
83. Hildemann WH, Raison RL, Cheung G, Hull CJ, Akaka L, Okamoto J: Immunological specificity and memory in a scleractinian coral. Nature 270:219, 1977
84. Grosberg RK, Quinn JF: The genetic control and consequences of kin recognition by the larvae of a colonial marine invertebrate. Nature 322:456, 1976
85. De Tomaso A, Saito Y, Ishizuka KJ, Palmeri KJ, Weissman IL: Mapping the genome of a model protochordate. I. A low resolution genetic map encompassing the fusion/histocompatibility (Fu/HC) locus of Botryllus schlosseri. Genetics 149:277, 1998
86. Burnet FM: "Self-recognition" in colonial marine forms and flowering plants in relation to the evolution of immunity. Nature 232:230, 1971 (link)
87. Williams JR, Lenington S: Factors modulating preferences of female house mice for males differing in t-complex genotype: role of t-complex genotype, genetic background, and estrous condition of females. Behavior Genetics 23:51, 1993
88. Potts WK, Manning CJ, Wakeland EK: Mating patterns in seminatural populations of mice influenced by MHC genotype. Nature 352:619, 1991 (link / PDF)
89. Ober C, Weitkamp LR, Cox N, Dytch H, Kostyu DD, Elias S: HLA and mate choice in humans. American Journal of Human Genetics 61:497, 1997
90. Wedekind C, Seebeck T, Bettens F, Paepke AJ: MHC-dependent mate preferences in humans. Proceedings of the Royal Society of London - Series B: Biological Sciences 260:245, 1995
91. Palm J: Maternal-fetal histoincompatibility in rats: an escape from adversity. Cancer Research 34:2061, 1974 (link)
92. Hamilton MS, Hellstrom I: Selection for histoincompatible progeny in mice. Biology of Reproduction 19:267, 1978 (link)
93. Wedekind C, Chapuisat M, Macas E, Rulicke T: Non-random fertilization in mice correlates with the MHC and something else. Heredity 77:400, 1996 (link)
94. Ober C, Elias S, Kostyu DD, Hauck WW: Decreased fecundability in Hutterite couples sharing HLA-DR. American Journal of Human Genetics 50:6, 1992 (link)
95. Jin K, Ho HN, Speed TP, Gill TJ III: Reproductive failure and the major histocompatibility complex. American Journal of Human Genetics 56:1456, 1995 (link)
96. Brown JL: Some paradoxical goals of cells and organisms: the role of the MHC, in Pfaff DW (ed): Ethical Questions in Brain and Behavior: Problems and Opportunities, New York, Springer-Verlag, 1983, p 111
Rosengarten & Nicotra (2011) Model Systems of Invertebrate Allorecognition. Current Biology (PMID: 21256442).
Research on allorecognition in Botryllus schlosseri in De Tomaso Laboratory
Last edited on 8 April 2013
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