Current Knowledge about Major Histocompatibility Complex - Essay Example

Review the current knowledge of how Major Histocompatibility Complex (MHC) genes evolve in response to selective pressure from pathogens, and how this may be influenced by social behaviour in animals. Abstract: MHC or major histocompatibility complex is characterized by immune responses. Genetic diversity is noted as the main feature of MHC and MHC is considered as the most polymorphic genetic system. MHC exercises a pathogen driven selection which is mediated through frequency dependent selection or heterozygote advantage. Thus the Major Histocompatibility Complex or MHC is responsible for selective pressure that adaptively maintains genetic diversity in natural populations. Some other influences of the MHC include mating preference, vulnerability to diseases, cooperation, kin recognition, individual odours and immune recognition. The role of immune responses and polymorphism brings about changes to parasitic responses and individuals master immune responses against pathogenic responses. In this discussion features of the major histocompatibility complex are highlighted and the mechanisms and functions of the immune system are also discussed in terms of pathogenic reactions and the role of the MHC. The importance of genetic diversity, selective pressure and polymorphism would also be discussed to suggest evolutionary changes, genetic diversity in the population and the influence of MHC on social behavior. Keywords: Major Histo compatibility complex (MHC), Selective pressure, Pathogens, Genetic diversity, Polymorphism. Introduction: A description of the MHC or Major Histocompatibility Complex could suggest that MHC is a gene cluster. The MH complex consists of four million base pairs of DNA and contains 128 genes as well as 96 pseudogenes (non-functional gene remnants). The MHC is thus a multigene family, has a large cluster of genes encoding key receptor molecules that aids in the binding of foreign peptides to immune cells and this in turn leads to a successful immune response (Klein, 1986). The vertebrate immune system has the MHC as its core and it is a multigene family encoding receptor molecules that binds and recognizes foreign peptides for immune responses and immune cells. The MHC tends to recognize foreign proteins, present them to immune cells and trigger a sort of immune response and foreign proteins enter cells by infection, phagocytosis in antigen presenting cells and macrophages. Foreign proteins are comprised of small peptides and presented in MHC molecules and these proteins are transported to the cell surface and T cell population. When the peptide binds the T cells, immune responses are triggered (Klein, 1986). The MHC is the most important genetic cluster within a mammalian immune system and the immune system is described in terms of the Major Histocompatibility Complex. The MHC is composed of cell surface glycoproteins and binds antigens from pathogens to T lymphocytes and this helps in triggering the appropriate immune response to attack of parasites in the body. Some MHC genes may produce a diversity of antigens in a population and individuals posses a unique bunch of genes and the MHC represent the immune system and immune responses quite directly so the genetic effects of population fragmentation are studied. Certain MHC genes evolve in response to selective pressure from pathogens and tend to affect the social behavior of animals as well. Some of the issues that will be discussed here would relate to the nature of MHC, the underlying structural and functional attributes, the early history of MHC, the class I, II, and III and variations or differentiation within manifestation of MHC so that evolutionary processes and mechanisms of parasitic reactions, adaptation and selection could be explained. The MHC has been characterized at the molecular level for many years and the population diversity of MHC molecules is quite large as for some MHC loci, over 100 different alleles have been identified (Parham and Ohta 1996). For polymorphism in MHC, the importance of mutation, recombination and selection is highlighted. The immune recognition of parasites and pathogens show that MHC is associated with quantitative traits that are linked to fitness and behavior of individuals and evolutionary dynamics is of some relevance in conservation and ecology. MHC diversity could be characterized in accordance with the mode of MHC evolution by examining relationships with ecological processes and evolutionary dynamics (Edwards et al, 1995) Some of the issues that could be highlighted in the discussion of immune responses would relate to host genetic diversity that buffers individuals against pathogenic reactions and aids in the prevention of widespread epidemics and major killer diseases. Pathogens tend to master certain evasive strategies within the immune system and body host cells counter such immunity as well. Parham and Ohta (1996) examine how every immune response could be separately distinguished and how polymorphism could bring about changes and advantages in parasitic responses. Parham and Ohta examine how immune responses emerge from populations of peptides, T cells and MHC molecules and how individuality of responses is shaped by MHC polymorphism. Polymorphism tends to confer differential advantages to parasitic responses and the selective pressures on the MHC are shown in the turnover of alleles. The role of mutation, recombination, selection and drift in generation of MHC polymorphism is considered (Hughes 1992; Clarke and Kirby, 1966). Genetic factors determine tissue compatibility and the dominant locus is the Major Histocompatibility complex. Most mammals have MHC structure and composition similar to that of humans. Gene families and molecules of MHC are found in all vertebrates, though the gene composition, gene variety, the genomic arrangement or arrangement of the genetic molecules tend to vary. There is an extreme diversity of genes of major histocompatibility complex or MHC and the structure and functions of classic MHC genes are well understood. The selective maintenance of MHC has to be deciphered especially considering that diversifying selections can be driven by pathogen interactions and inbreeding mechanisms. Heterozygote advantage and frequency dependent selection tend to maintain pathogen driven selection and MHC polymorphism. MHC haplotypes can be resistant to infectious agents which precipitate autoimmunity and also contributes to MHC diversity, molecular mimicry and immunodominance (Apanius et al, 1997). The MHC dependent abortion and mate choice could lead to MHC diversity and functions to avoid inbreeding to produce MHC heterozygous offspring with increased immune responsiveness. These mechanisms operate in some and extreme diversification is found in MHC genes. If MHC diversity is explained with rapidly evolving parasites, then there are MHC-dissortative mating preferences that provide moving target to parasites evading immune recognition. The balance of selective pressures constantly varies in this case and adaptive responses may be mutually opposed to each other. Major Histocompatibility Complex The early history of MHC could be associated with tumors. Systematic analysis of alloantibodies (serology) generated by immunizations involving different combinations of mice strains allowed serologists to define several independent groups of allo-antigens, including the MHC (second group found in mice; H-2). It was observed that when tumors were transplanted from sick mice to healthy mice, did not grow but were rejected by the immune system. But, when tumors were used on inbred strains of mice, successful transplantation and propagation of tumors became possible. This suggests one or more genetic factors control acceptance or rejection of tumors. When mice of one strain were transplanted or immunized with cells from a second strain, alloantibodies were formed against the MHC glycoproteins of the second strain and this could be the primary factor for tissues which are accepted or rejected by the immune system. Further research revealed that in the same way as in case of tumours, transplanted healthy tissues could also be immunologically rejected. The MHC is divided into the MHC class I, MHC class II, and MHC class III regions, each containing different groups of genes with related functions. Class I All nucleated cells except sperm cells and some neurons tend to have MHC molecules on the surface and present fragments of proteins that are synthesized inside the cell. The peptide antigens are controlled by killer T-cells, which have receptors for the Class I MHC proteins. Class II MHC proteins tend to engulf foreign particles such as bacteria. The cells use peptide antigens derived from digested particles and the antigens are taken to T-cells, which have receptors for class II MHC proteins. The immune system maintains control over the body with the help of MHC proteins. Class III This type of genes encode soluble proteins and target foreign cells to break open the membranes, so that immune responses can begin. A group of genes close to the Class III genes also manifest an immune response in the form of controlling inflammation. The complex has genes with both immune and non-immune functions. The class I and II MHC genes encode human leukocyte antigens (HLAs), proteins that are found on the surface of the cells and define an individual's tissue type controlling several immune responses. The genetic architecture of the MHC has been given for several model vertebrate species, such as mouse, rat (Gunther and Walter, 2001). The class I and class II genes are linked together in a single gene complex (Hess and Edwards, 2002). The human MHC structure tends to vary and the MHC complex is found in chickens with 19 genes although there are similarities across these model systems in MHC. The MHC genes have diverse traits and functions and the MHC structure and functions tend to explain the selective processes, the immune responses and molecular adaptation in vertebrates. MHC variation is maintained by the selective effect of different pathogens. MHC diversity has ecological significance and even the different pathogens show selective effects triggering the need for MHC to have different selective responses. Evidence of selection of balancing of the MHC genes has been found at different temporal scales. Genetic diversity is thus explained with MHC and is an essential aspect of biology, conservation, ecology and population genetics. The variations in genes on the MHC helps in bringing about a) variations in immune responses, b) diversity in the genetic makeup of the organisms, c) differences in selective processes and d) molecular adaptation mechanisms. Among all genetic complexes and structures, the MHC contains the most variable functional genes and is the most diversified among vertebrates. High genetic diversity and variation is a feature of the MHC. The MHC is associated with certain quantitative traits that can explain social behavior as well as fitness and other traits among animals and vertebrates. The reason for the high genetic variability in the major histocompatibility complex (MHC) is not entirely known and reports suggest that females may prefer to mate with males who are different at the MHC (Hedrick, 1992). The mechanisms or rationale of female choice could be studied further and can reduce observed proportions of homozygotes and maintain the genetic polymorphism. Mating types frequencies are influenced by the genetic variations and tend to generate some form of disequilibrium. MHC variability has many advantages and help in the study of evolutionary and adaptive processes in population and aids in the understanding of balancing selection and evolutionary ecology and conservation. The genes of the MHC also help in recognizing the lifespan genetics and also highlight the reasons for inter and intra species differentiation and diversification along with the selective processes in evolution. MHC diversity and variations are factors associated with social behavior as in fitness, population viability, and evolutionary potential in a changing environment. Thus MHC not only determines and exemplifies genome diversity but also shows how this diversity could be used to describe evolution and social behavior of animals in accordance with environmental changes. MHC variability could help in understanding the process of balancing selection in ecology. Two main types of balancing selection are (1) Heterozygote advantage hypothesis (2) Frequency-dependence selection Both these types of selection help in retention of genetic diversity in humans and vertebrates. Genetic diversity is maintained by a process of diversifying selection and a number of alleles have been observed in all vertebrates and are distributed within populations and non synonymous substitution is higher than synonymous substitution. When a large number of different MHC molecules are present, heterozygous individuals can detect a wide range of pathogen driven antigens. MHC usually places human linked antigens within the system and MHC heterozygotes bring in a diversity of antigens to the immune system than the homozygotes (Doherty and Zinkernagel 1975). Heterozygotes also have variant alleles and this can lead to a broader range of functions and identification of pathogens. This could be explained with several examples. Knowledge of dominance' and over dominance could analyze the evolutionary mechanism of the heterozygote advantage. MHC heterozygotes are more resistant to parasites than homozygotes, so considering selective and adaptive processes, MHC dissortative mating preferences will subsequently be favored as a mechanism to produce MHC-heterozygous offspring (Jordan and Bruford, 1998). The frequency dependent mechanism occurs when an allele is favoured at one frequency, but not at another frequency (Klein and O'Hugin, 1994). Thus, the frequency-dependent selection hypothesis is also described as 1. Rare-allele advantage hypothesis, 2. Red Queen hypothesis or 3. Moving-target hypothesis. The MHC-dependent mating preferences may enhance the immunity of an individual's progeny, depending on how parasites impose selection on MHC alleles. Parasites can heighten MHC diversity, through heterozygote advantage, and selection or adaptive processes would favor MHC dependent mating preferences (Jordan and Bruford, 1998; Edwards and Hedrick, 1998). The fundamental role of the MHC is combating attacks from parasites and pathogens which brings in the concept that MHC polymorphism maintained through pathogen-driven selection (Doherty and Zinkernagel, 1975; Hedrick and Kim, 1998). The evolution and maintenance of MHC polymorphism could be related to the defensive mechanisms used by the host immune system and how the MHC helps against the attack of infectious parasites. MHC plays a central role in the immune system as we have already discussed and the parasites tend to maintain the diversity of MHC alleles providing variations and changes within the complex (Frank, 1996). MHC heterozygotes have various alleles which help in the identification of different pathogens and this helps in protection against multiple parasites. MHC heterozygotes tend to recognize a parasite better than homozygotes and this affects the social behavior of vertebrates. It is assumed that MHC polymorphisms are maintained because populations with high MHC diversity have a better chance of survival than populations with low diversity and this is again a selective and adaptive mechanism showing the manifestation of different species and a strategy to keep parasites from spreading through the population (Klein and O'Huigin, 1994). The balance of selective pressures constantly varies in this case and adaptive responses may be mutually opposed to each other. Thus maintaining genetic diversity would be the primary motivation for such a biological process and would also throw light on the social behavior, mating processes and relative fitness of organisms. The fundamental role of the MHC however is combating attacks from parasites and pathogens which brings in the concept that MHC polymorphism maintained through pathogen-driven selection (Doherty and Zinkernagel, 1975; Hedrick and Kim, 1998). Clarke and Kirby (1966) suggested that transplantation antigens represent genetic polymorphism and antigenic diversity is considered as a consequence of differences between individuals. During gestation the fetal homograft tend to face a mother-fetus barrier and antigenic differences between the fetus and mother could lead to effects of blood group incompatibility. Maintenance of balanced polymorphism is one of the aims of MHC and alleles within MHC tend to show associations with nematode resistance. Variations in the MHC are observed due to genetic variations especially in nematode infection and particular alleles tend to have specific effects. Heterozygotes tend to be more resistant than homozygotes and maintain high levels of polymorphism in the MHC (Stear et al, 2005). Selective forces work on MHC loci to maintain MHC variation and statistical tests are used for selection of DNA sequences. Detecting selection in contemporary populations can have a detectable effect on genotypic frequencies. Heterozygote genotypes have been considered as fitter than homozygote genotypes and a broader range of pathogens are usually identified (Doherty and Zinkernagel, 1975). Potts et al (1991) noted deficiencies in MHC homozygotes and suggested that selection is temporally variable and lack allelic diversity at the MHC. Potts and Slev (1995) presented the ways in which pathogens favor the evolution of MHC genetic diversity and each model makes unique predictions and prevents distinguishing the relative importance of each model. MHC dependent immune recognition is considered escape proof by pathogens although the models of pathogen escape may not work and can even lead to frequency dependent selection although Potts and Slev (1995) claim that heterozygote advantage is a consequence of pathogen evasion. The Major Histocompatibility complex tends to play a critical role in kin recognition through mating and cooperation and the MHC is important for understanding the evolution of kin recognition in the context of genetics and cell biology. Certain genes tend to code MHC glycoproteins in a diverse manner and the mechanisms of selection for allelic diversity of MHC are controversial although there are behavioral mechanisms of dissortative mating and inbreeding avoidance (Brown and Eklund, 1994). Behavior, genetics and molecular genetics tend to be integrated within the context of natural selection and evolution. Paterson (1998) discussed the evidence for selective maintenance of genetic diversity at the major histocompatibility complex or MHC in a population and sampled newborn lambs with microsatellite markers located within MHC. Markers in the MHC showed high levels of linkage disequilibrium and the MHC showed relatively even allele distributions and suggests the mechanism of balancing selection. Sequence polymorphism tends to correlate with microsatellite length variation and non synonymous substitution has been found to be higher than synonymous substitution indicating the action of balancing selection favoring MHC variants with increased diversity over a long period of time. Gunther and Walter (2001) focused on the major histocompatibility complex or MHC of the rat and determined the genetic, genomic, evolutionary and functional aspects of MHC. The analysis showed an orthologous relationship between human and mouse MHC. The rat is used as a model of experimental transplantation and complex diseases. Several studies have shown that mate choice decisions are closely linked to MHC and they can be made on the basis of individual genotypes at the major histocompatibility complex or MHC that accords with the immunocompetence of sexual selection. MHC based mate choice varies across species as a result of differences in social and mating system structure as well as genome structure. A preference is expressed for MHC dissimilar mates and MHC dissortative mating and in maintaining MHC and genome wide variety (Jordan and Bruford, 1998). The strength and direction of MHC mating preference vary and factors such as genetic background, sex, life experiences tend to influence mating choices. Discussion and Conclusion: Different species tend to show adaptive responses that can cause a problem when advantage of one may become a problem for another and a parasite and host may also show conflicts in adaptation. MHC genes tend to increase adaptive and selective processes and are resistant to parasites and along with the parasite, there may be changes to the fitness of the host bringing out issues of selective advantage. The MHC alleles play a significant role in increasing and decreasing fitness of organisms and antagonistic co-evolutionary responses leads to differing fitness values and maintain high genetic diversity. Some of the future directions towards MHC diversity shows that MHC diversity could be used in the context of conservation and helps in the study of evolution, selection and adaptation. Levels of MHC diversity could be related to selective mechanisms within natural environments and evolutionary relationships bring out links between MHC diversity and parasites, individual fitness, mating choice and reproductive success. MHC diversity is manifested between populations and infer variations across populations. The three main areas for future lines of research show: 1. Information that detects the action of selection on MHC genes 2. The contributions of parasite mediation, and 3. Sexual selection on maintenance of MHC diversity The development of rapid, high throughput screening techniques has led to the possibility of examining a large number of individuals for MHC variation. Some of these techniques are (1) SSCP -single-stranded conformational polymorphism (2) DGGE- denaturing gradient gel electrophoresis Some of the issues that have been touched upon in this discussion relate to the genetic variation and differences in the MHC. Here we have identified the different classes of the MHC genes, namely class I, II and III and sought out the variations in the functional and structural approaches both in these three classes of genes and in the general pattern of MHC gene complex. The MHC diversity sheds light on selection, adaptation, mating choices as well as social behavior in a natural environment. Parasitic reactions tend to affect immune reactions and the presence of MHC highlights how parasites, polymorphism and immune reactions are related. The evolution of MHC and polymorphism has become clear with an understanding of MHC in all types of vertebrates. The MHC is thus considered as large gene cluster with the genes located in the chromosomal part that seem to be affected by adaptive and selective mechanism and are mediated by immune responses. The social behavior of animals could be explained with genetic variations in the MHC and even the evolutionary patterns of vertebrates tend to change in accordance with the variation of MHC. MHC variants tend to influence the mating preferences and social behavior as well as immune responses and recognition and autoimmune disease manifestations in organisms. 1400 alleles of genes within the human major histocompatibility complex are recognized and human leukocyte antigen or HLA are performed for hematopoietic stem cell transplantation (Leffell, 2002). Molecular typing techniques have serological reactivity and ambiguous allele assignments and inconsistent correlation of alleles could result in sharing of motif with other allele groups. Many alleles can share identical sequences in the regions of HLA genes that are sequenced. Ambiguities occur when combinations of different alleles are considered and failure to recognize antigens or inconsistent antigen specificity could result in mismatches in transplant recipient and ambiguities will have to be resolved (Leffell, 2002). One of the future directions of major histocompatibility complex would be recognizing allele sequences and ambiguities in cell transplantation. This might be possible with the use of different techniques which can help in resolving ambiguities and minimizing costs. Studies on parasite driven selection are expected to focus on variation of alleles, variation of pathogens and allele frequencies. MHC dependent mating preferences enhance immunity of individual progeny and selection is dependent on MHC alleles. Parasites seem to influence diversity of MHC and selection favors MHC dependent mating preferences that tend to avoid inbreeding and uphold the good genes sexual selection. The studies on MHC help in improving understanding the adaptive genetic variability and focus on mammalian variations and the role of MHC in ecology. The adaptive genetic diversity of the population and the mechanisms of selection and selective pressures would be related to the significance of the study of MHC. The study of MHC gene polymorphism provides a common thread for assessing the strength of selection for resistance to parasites in different environments. The focus of this study however has been on how MHC responds to selective pressure from pathogens and in this context the social behavior of animals seems to play a central role. This study reiterates existing findings that MHC and immune responses are related and that it has a deep and significant impact on evolutionary biology. This discussion has primarily focused on the nature of the immune responses and the role of the major histocompatibility complex. The MHC is considered as a large gene cluster found within the chromosome and helps to recognize foreign peptides bringing about immune responses. The evolutionary and functional aspects of genome responses show how the MHC could have a wide range of influences and even play a role in the context of social behavior through these evolutionary and genetic functions. Parasites and pathogens are dealt with and the MHC also seems to affect mating choices and social behavior within vertebrates by maintaining selective pressure and genetic diversity within the population. The genetic variations of MHC allow for individual immune responses against pathogens and the MHC thus tend to have multiple functions of selection, immunity, and social behavior through genetic variability. Bibliography Apanius, V., D. Penn, P. Slev, L. R. Ruff, and W. K. Potts.1997. The nature of selection on the major histocompatibility complex. Critical Reviews in Immunology 17:179-224. Bodmer WF (1972). Evolutionary significance of the HL-A system. Nature 237:139-145 Boehm T, Zufall F. (2006) MHC peptides and the sensory evaluation of genotype. Trends Neurosci. Feb;29(2):100-7. Epub 2005 Dec 6. Brown Jerram L., Eklund Amy (1994) Kin Recognition and the Major Histocompatibility Complex: An Integrative Review The American Naturalist, Vol. 143, No. 3., pp. 435-461 Clarke, B., and D. R. S. Kirby. 1966. Maintenance of histocompatibility polymorphisms. Nature (London) 211:999-1000. Doherty PC, Zinkernagel RM (1975). Enhanced immunological surveillance in mice heterozygous at the H-2 gene complex. Nature 256: 50-52. Dreau D.;Sonnenfeld G.;Fowler N.;Morton D.S.;Lyte M. (1999) Effects of Social Conflict on Immune Responses and E. coli Growth within Closed Chambers in Mice - The role of blood loss Physiology and Behavior, Volume 67,Number 1, pp. 133-140(8) Edwards SV, Grahn M, Potts WK (1995). Dynamics of MHC evolution in birds and crocodilians - amplification of class-ii genes with degenerate primers. Mol Ecol 4: 719-729. Freeman-Gallant C.R.;Meguerdichian M.;Wheelwright N.T.;Sollecito S.V. (2003) Social pairing and female mating fidelity predicted by restriction fragment length polymorphism similarity at the major histocompatibility complex in a songbird Molecular Ecology, Volume 12,Number 11, pp. 3077-3083(7) Gunther E, Walter L (2001). The major histocompatibility complex of the rat (Rattus norvegicus). Immunogenetics 53: 520-542. Hambuch TM, Lacey EA. (2002) Enhanced selection for MHC diversity in social tuco-tucos. Evolution Int J Org Evolution. Apr;56(4):841-5. Harris H (1966). Enzyme polymorphism in man. Proc Roy Soc London B 164: 298-310. Hedrick, P. W. 1992. Female choice and variation in the major histocompatibility complex. Genetics 132: 575-581. Hess CM, Edwards SV. The evolution of the major histocompatibility complex in birds. Bioscience. 2002;52:423-431. Hughes,AustinL.; Nei,Mastoshi (1992). Maintenance of MHC polymorphism Nature, Volume 355, Issue 6359, pp. 402-403 Janeway CA (1993) How the immune system recognizes invaders. Sci Am. Sep;269(3):72-9. Jordan WC, Bruford MW. (1998) New perspectives on mate choice and the MHC. Heredity. Aug;81 ( Pt 2):127-33. Klein J (1986). Natural History of the Major Histocompatibility Complex, 1st edn. John Wiley & Sons: New York, Chichester, Brisbane, Toronto, Singapore. Klein, J., and C. O. O'Huigin. (1994). MHC polymorphism and parasites. Philosophical Transactions of the Royal Society of London B, Biological Sciences 346:351-358 Kundu, S. & Faulkes, C.G. 2004 Patterns of MHC selection in African mole-rats (Family Bathyergidae): the effects of sociality and habitat. Proc. R. Soc. Lond. B. 271, 273-278. Leffell Mary S. (2002) MHC polymorphism: Coping with the allele explosion Clinical and Applied Immunology Reviews,Volume 3, Issues 1-2, Pages 35-46 LUKAS D.;BRADLEY B. J.;NSUBUGA A. M.;DORAN-SHEEHY D.;ROBBINS M. M.;VIGILANT L. (2004) Major histocompatibility complex and microsatellite variation in two populations of wild gorillas Molecular Ecology, Volume 13,Number 11, pp. 3389-3402(14) Parham P & Ohta T (1996). Population biology of antigen presentation by MHC class I molecules. Science 272:67-74 Paterson S (1998) Evidence for balancing selection at the major histocompatibility complex in a free-living ruminant Journal of Heredity, Volume 89,Number 4, pp. 289-294(6) Potts, W.K., Wakeland, E.K. (1990) Evolution of diversity at the major histocompatibility complex. Trends in Ecology and Evolution 5:181-187. Potts, W.K., Wakeland, E.K.(1990) The maintenance of MHC polymorphism. Immunology Today 11:39-40. Potts WK, Slev PR. (1995) Pathogen-based models favoring MHC genetic diversity. Immunol Rev. Feb;143:181-97. Schaffer, E., A. Sette, D. L. Johnson, M. C. Bekoff, J. A. Smith, H. M. Grey, and S. Buus. 1989. Relative contribution of "determinant selection" and "holes in the T cell repertoire" to T-cell responses. Proceedings of the National Academy of Sciences of the USA .4649-4653. Sommer, S.;Tichy, H. (1999) Major histocompatibility complex (MHC) class II polymorphism and paternity in the monogamous Hypogeomys antimena, the endangered, largest endemic Malagasy rodent Molecular Ecology, Volume 8,Number 8, pp. 1259-1272(14) Stear MJ, Innocent GT, Buitkamp J. (2005) The evolution and maintenance of polymorphism in the major histocompatibility complex. Vet Immunol Immunopathol. Oct 18;108(1-2):53-7. Taylor, Maria;Prez-Meja, Amelia;Yamamoto-Furusho, Jess;Granados, Julio (1997) Immunologic, genetic and social human risk factors associated to histoplasmosis: Studies in the State of Guerrero, Mexico Mycopathologia, Volume 138,Number 3, pp. 137-141(5) Roy, S., M. T. Scherer, T. J. Briner, J. A. Smith, and M. L.Gefter. 1989. Murine MHC polymorphism and T-cell specificities. Science (Washington, D.C.) 244:572-575. Wilson, K., Knell, R. K., Boots, M. & Koch-Osbourne, J. 2003 Group-living and investment in immune defence: an inter-specific analysis. J. Anim. Ecol. 72, 133-143. Yamazaki, K., G. K. Beauchamp, J. Bard, and E. A. Boyse. 1996. Odortypes in the governance of social interactions. Behavioral Genetics 26:602 Read More