scholarly journals Polymorphism and balancing selection at major histocompatibility complex loci.

Genetics ◽  
1992 ◽  
Vol 130 (4) ◽  
pp. 925-938 ◽  
Author(s):  
N Takahata ◽  
Y Satta ◽  
J Klein
Keyword(s):  
Major Histocompatibility Complex ◽  
Dna Sequences ◽  
Balancing Selection ◽  
Heterozygote Advantage ◽  
Nucleotide Substitution Rate ◽  
Major Histocompatibility ◽  
Effective Population ◽  
Nucleotide Substitutions ◽  
Mhc Genes ◽  
Histocompatibility Complex

Abstract Amino acid replacements in the peptide-binding region (PBR) of the functional major histocompatibility complex (Mhc) genes appear to be driven by balancing selection. Of the various types of balancing selection, we have examined a model equivalent to overdominance that confers heterozygote advantage. As discussed by A. Robertson, overdominance selection tends to maintain alleles that have more or less the same degree of heterozygote advantage. Because of this symmetry, the model makes various testable predictions about the genealogical relationships among different alleles and provides ways of analyzing DNA sequences of Mhc alleles. In this paper, we analyze DNA sequences of 85 alleles at the HLA-A, -B, -C, -DRB1 and -DQB1 loci with respect to the number of alleles and extent of nucleotide differences at the PBR, as well as at the synonymous (presumably neutral) sites. Theory suggests that the number of alleles that differ at the sites targeted by selection (presumably the nonsynonymous sites in the PBR) should be equal to the mean number of nucleotide substitutions among pairs of alleles. We also demonstrate that the nucleotide substitution rate at the targeted sites relative to that of neutral sites may be much larger than 1. The predictions of the presented model are in surprisingly good agreement with the actual data and thus provide means for inferring certain population parameters. For overdominance selection in a finite population at equilibrium, the product of selection intensity (s) against homozygotes and the effective population size (N) is estimated to be 350-3000, being largest at the B locus and smallest at the C locus. We argue that N is of the order of 10(5) and s is several percent at most, if the mutation rate per site per generation is 10(-8).

Evolutionary Relationships of Major Histocompatibility Complex Class I Genes in Simian Primates

Genetics ◽  
2004 ◽  
Vol 166 (4) ◽  
pp. 1897-1907
Author(s):  
Hiromi Sawai ◽  
Yoshi Kawamoto ◽  
Naoyuki Takahata ◽  
Yoko Satta
Keyword(s):  
Major Histocompatibility Complex ◽  
Distinct Group ◽  
Gene Organization ◽  
Class I ◽  
Phylogenetic Position ◽  
Specific Gene ◽  
New World Monkeys ◽  
Major Histocompatibility ◽  
Nucleotide Substitutions ◽  
Histocompatibility Complex

Abstract New World monkeys (NWMs) occupy a critical phylogenetic position in elucidating the evolutionary process of major histocompatibility complex (MHC) class I genes in primates. From three subfamilies of Aotinae, Cebinae, and Atelinae, the 5′-flanking regions of 18 class I genes are obtained and phylogenetically examined in terms of Alu/LINE insertion elements as well as the nucleotide substitutions. Two pairs of genes from Aotinae and Atelinae are clearly orthologous to human leukocyte antigen (HLA) -E and -F genes. Of the remaining 14 genes, 8 belong to the distinct group B, together with HLA-B and -C, to the exclusion of all other HLA class I genes. These NWM genes are classified into four groups, designated as NWM-B1, -B2, -B3, and -B4. Of these, NWM-B2 is orthologous to HLA-B/C. Also, orthologous relationships of NWM-B1, -B2, and -B3 exist among different families of Cebidae and Atelidae, which is in sharp contrast to the genus-specific gene organization within the subfamily Callitrichinae. The other six genes belong to the distinct group G. However, a clade of these NWM genes is almost equally related to HLA-A, -J, -G, and -K, and there is no evidence for their orthologous relationships to HLA-G. It is argued that class I genes in simian primates duplicated extensively in their common ancestral lineage and that subsequent evolution in descendant species has been facilitated mainly by independent loss of genes.

scholarly journals Major Histocompatibility Complex Genes as Therapeutic Opportunity for Immune Cold Molecular Cancer Subtypes

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Paweł Karpiński ◽  
Łukasz Łaczmański ◽  
Maria M. Sąsiadek
Keyword(s):  
Major Histocompatibility Complex ◽  
Expression Patterns ◽  
Unsupervised Clustering ◽  
Tumor Rejection ◽  
Molecular Heterogeneity ◽  
Tumor Type ◽  
Major Histocompatibility ◽  
Cancer Subtypes ◽  
Mhc Genes ◽  
Histocompatibility Complex

Current immunotherapies are effective only in a subset of patients, likely due to several factors including defects in tumor cell antigen presentation, decreased response to immune effectors, and molecular heterogeneity of cancers. Recent molecular classifications enable the categorization of many tumor types. However, deregulation of major histocompatibility complex (MHC) gene expression is poorly characterized in the context of molecular cancer subtypes. To suppress the confounding effect of immune infiltrates on expression patterns of immunoregulators, we identified and removed genes with strong correlation to estimated immune compartment levels in each tumor type. Next, we reanalyzed a total of 13 TCGA cancer types encompassing 5651 tumors and 485 normal adjacent tissues by performing unsupervised clustering of 14 MHC genes. Subsequently, resultant clusters were statistically compared in terms of expression of other immune-related genes. Three MHC expression clusters were discovered by unsupervised clustering. We identified concordantly decreased expression of MHC genes (MHC-low) in 26 out of 55 molecular subtypes. Consequently, our study underlines the urgent need for designing strategies to enhance tumor MHC expression that could improve immune cold tumor rejection by cytotoxic T lymphocytes.

scholarly journals Influence of major histocompatibility complex (MHC) on human mating preferences

2017 ◽  
Vol 10 (2) ◽  
Author(s):  
Anvita Kulshrestha
Keyword(s):  
Major Histocompatibility Complex ◽  
Good Genes ◽  
Major Histocompatibility ◽  
Chi Square ◽  
Mating Preferences ◽  
Mhc Genes ◽  
Histocompatibility Complex ◽  
Il Y A ◽  
Chi Square Test ◽  
Human Mating

Several studies related to vertebrates have revealed that highly polymorphic genes within the Major Histocompatibility Complex (MHC) may play a role in mate choice. Females gain direct or indirect fitness benefits by choosing between males with traits that are expressed from good genes, as females can obtain good genes for their offspring by mating with males whose genes are compatible or complementary to their own. There is a tendency for humans to prefer MHC-dissimilar mates, as it would favour the production of heterozygous offspring who would be more resistant to pathogens. This phenomenon has been reviewed on the similar concepts of the influence of MHC genes on human mating preferences, with potential but largely unknown in offspring fitness. The qualitative method can include surveying and interviewing people about their mate choices i.e. females select males with heterozygosity MHC genes over males with homozygous MHC genes. Chi-square test can be performed for statistical analysis. Mating with a MHC dissimilar individual can produce MHC heterozygous offspring that has strong immunocompetence against several parasite types. A heterozygous MHC gene combination has more capability to identify rapidly evolving parasites, which can escape recognition by immune systems containing common alleles.Plusieurs études reliées aux vertébrés ont révélé que les gènes extrêmement polymorphes au sein du complexe majeur d’histocompatibilité (MHC) peuvent jouer un rôle dans le choix d’un partenaire. Les femmes tirent des avantages directs ou indirects de valeur sélective en choisissant entre les hommes dont les traits sont exprimés avec les bons gènes, comme les femmes peuvent obtenir de bons gènes pour leur progéniture par accouplement avec des mâles dont les gènes sont compatibles ou complémentaires à leurs propres. Il y a une tendance pour les humains de préférer les camarades MHC-dissemblables, car ceci favoriserait la production de descendants hétérozygotes qui seraient plus résistants aux pathogènes. Ce phénomène était étudié sur les concepts similairesde l’influence des gènes du MHC sur les préférences d’accouplement humaines, avec un potentiel largement inconnu dans la valeur sélective de la progéniture. La méthode qualitative peut comprendre une enquête et l’interrogation des gens sur leur choix de partenaire, par ex. les femelles choisissent les mâles avec des gènes du CMH hétérozygote sur les hommes ayant des gènes du CMH homozygotes. Le test du chi carré peut être effectué pour faire l’analyse statistique. L’accouplement avec une personne avec un différent CMH peut produire la progéniture CMH hétérozygote qui a une forte immunocompétence contre plusieurs types de parasites. Une combinaison de gènes CMH hétérozygotes a plus de capacité d’identifier les parasites qui évoluent rapidement, qui peuvent échapper à la reconnaissance par le système immunitaire contenant des allèles communs.

Detection of host DNA sequences including the H-2 locus of the major histocompatibility complex in schistosomes

Parasitology ◽  
1995 ◽  
Vol 110 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Y. Iwamura ◽  
H. Yonekawa ◽  
Y. Irie
Keyword(s):  
Major Histocompatibility Complex ◽  
Dna Sequences ◽  
Major Histocompatibility ◽  
Male Adult ◽  
Class I Mhc ◽  
Mouse Major Histocompatibility Complex ◽  
Histocompatibility Complex ◽  
Pcr Products ◽  
Primer Sets ◽  
Host Parasite

SUMMARYThe mouse type 2 Alu (B2) sequence was detected in both DNAs of Schistosoma mansoni and S. japonicum except for the cercarial stage by the polymerase chain reaction (PCR). Using several kinds of mouse STMS (sequence tagged microsatellite site) primer sets, PCR products related to the host were found in the DNAs of S. mansoni as well as of S. japonicum. Products could be detected only in the DNA of S. japonicum using certain STMS primer sets. The fact that no products could be amplified from the DNAs of both parasites when other kinds of STMS primer sets were used suggests unequal incorporation of the host DNA into the schistosomes. Furthermore, the sequence of the N-terminal domain of H-2, the mouse major histocompatibility complex (MHC), was detected in the DNAs from S. mansoni miracidium, male adult and S. japonicum adults, whereas the sequence of the C2 domain of H-2 was found only in the DNAs of S. japonicum adults. This evidence that host DNA sequences, including the class I MHC, exist heterogeneously in the DNAs of schistosomes might provide an important insight for further understanding of host-parasite immune interactions.

Sign in / Sign up

Export Citation Format

Share Document