Pinpointing a selective sweep to the chimpanzee MHC class I region by comparative genomics

Groot, Natasja G. de; Heijmans, Corrine M. C.; Groot, Nanine de; Otting, Nel; Vos-Rouweler, Annemiek J. M. de; Remarque, Edmond J.; Bonhomme, Maxime; Doxiadis, Gaby G. M.; Crouau‐Roy, Brigitte; Bontrop, Ronald E.

doi:10.1111/j.1365-294x.2008.03716.x

Cited by 46 publications

(57 citation statements)

References 73 publications

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“…Low genetic variation is also seen at devil class I genes (Siddle et al 2010), although the allelic richness and sequence divergence are higher at class I loci compared to class II. A similar process appears to have occurred in chimpanzees where a selective sweep, which may have been caused by a simian immunodeficiency virus and primarily targeted MHC class I genes, resulted in a severe reduction of allelic repertoire at these loci and also affected other polymorphic loci near the class I region due to genetic linkage (de Groot et al 2002(de Groot et al , 2008. In the devil, it is hard to pinpoint the direct target of the selective sweep as class I and class II genes are tightly linked (Cheng et al 2012), which means the sweep could have taken place in either region and affected the other through linkage.…”

Section: Discussionmentioning

confidence: 84%

Low MHC class II diversity in the Tasmanian devil (Sarcophilus harrisii)

et al. 2012

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The largest remaining carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii), is currently under threat of extinction due to a fatal contagious cancer-devil facial tumour disease. Low major histocompatibility complex (MHC) class I diversity is believed to have contributed to the transmission of the tumour allograft through devil populations. Here, we report low MHC class II variability in this species, with DA β chain genes (Saha-DAB1, 2 and 3) exhibiting very limited diversity and the sole α chain gene (Saha-DAA) monomorphic. Three, six and three alleles were found at Saha-DAB1, 2 and 3, respectively, with a predominant allele found at each locus. Heterozygosity at these three loci is low in the eastern population and modestly higher in northwestern individuals. The results are indicative of a selective sweep likely due to an infectious disease resulting in the fixation of selectively favoured alleles and depletion of genetic diversity at devil class II loci. Several attempts were made to isolate the other marsupial classical class II gene family, namely, DB, resulting in only one DBB pseudogene being found. These findings further support the view that this species has a compromised capacity to respond to pathogen evolution, emerging infectious diseases and environmental changes.

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Section: Discussionmentioning

confidence: 84%

Low MHC class II diversity in the Tasmanian devil (Sarcophilus harrisii)

et al. 2012

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“…The HLA-DR region is exceptional, since it encompasses a highly conserved DRA gene, encoding the DR alpha chain, in conjunction with a different number and combination of DRB genes, which encode the beta chains. Such copy number variation is observed not only with the human population but is even more prominently present in great apes such as in chimpanzees (15) and in Old World monkeys such as rhesus and cynomolgus macaques (19)(20)(21). The HLA-DR region configuration contains pseudogenes, and orthologous structures have been detected in many primate species (10).…”

Section: Discussionmentioning

confidence: 99%

“…The DR region in particular has been subject to several expansion and contraction processes, resulting in the generation of various regional configurations characterized by the presence of differential gene copy numbers (1, 13, 27-30, 35, 38, 41, 47, 53, 62-65). In humans, five DRB region configurations are known, whereas in chimpanzees and rhesus macaques, 6 and more than 30 such configurations have been determined, respectively (13,15,20,51,53,73). A schematic illustration of the organization of the HLA-DR region has been provided (Fig.…”

mentioning

confidence: 99%

Impact of Endogenous Intronic Retroviruses on Major Histocompatibility Complex Class II Diversity and Stability

Doxiadis

Groot

Bontrop

2008

J Virol

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The major histocompatibility complex (MHC) represents a multigene family that is known to display allelic and gene copy number variations. Primate species such as humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta) show DRB region configuration polymorphism at the population level, meaning that the number and content of DRB loci may vary per haplotype. Introns of primate DRB alleles differ significantly in length due to insertions of transposable elements as long endogenous retrovirus (ERV) and human ERV (HERV) sequences in the DRB2, DRB6, and DRB7 pseudogenes. Although the integration of intronic HERVs resulted sooner or later in the inactivation of the targeted genes, the fixation of these endogenous retroviral segments over long time spans seems to have provided evolutionary advantage. Intronic HERVs may have integrated in a sense or an antisense manner. On the one hand, antisense-oriented retroelements such as HERV-K14I, observed in intron 2 of the DRB7 genes in humans and chimpanzees, seem to promote stability, as configurations/alleles containing these hits have experienced strong conservative selection during primate evolution. On the other hand, the HERVK3I present in intron 1 of all DRB2 and/or DRB6 alleles tested so far integrated in a sense orientation. The data suggest that multigenic regions in particular may benefit from sense introgressions by HERVs, as these elements seem to promote and maintain the generation of diversity, whereas these types of integrations may be lethal in monogenic systems, since they are known to influence transcript regulation negatively.

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“…An important species difference is the loss of polymorphisms in class IA and B genes in humans. This implies a class-specific loss of variation and therefore a selective elimination of responses against specific families of epitopes (de Groot et al, 2008). Also a pertinent difference in PRRs has been reported (Brinkworth et al, 2012).…”

Section: Are Primate Studies Predictable For Humans?mentioning

confidence: 99%

Immunological and Technical Considerations in Application of Alginate-Based Microencapsulation Systems

Juárez¹,

Spasojević²,

Faas³

et al. 2014

Front. Bioeng. Biotechnol.

151

128

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Islets encapsulated in immunoprotective microcapsules are being proposed as an alternative for insulin therapy for treatment of type 1 diabetes. Many materials for producing microcapsules have been proposed but only alginate does currently qualify as ready for clinical application. However, many different alginate-based capsule systems do exist. A pitfall in the field is that these systems are applied without a targeted strategy with varying degrees of success as a consequence. In the current review, the different properties of alginate-based systems are reviewed in view of future application in humans. The use of allogeneic and xenogeneic islet sources are discussed with acknowledging the different degrees of immune protection the encapsulation system should supply. Also issues such as oxygen supply and the role of danger associated molecular patterns (DAMPS) in immune activation are being reviewed. A common property of the encapsulation systems is that alginates for medical application should have an extreme high degree of purity and lack pathogen-associated molecular patterns (PAMPs) to avoid activation of the recipient’s immune system. Up to now, non-inflammatory alginates are only produced on a lab-scale and are not yet commercially available. This is a major pitfall on the route to human application. Also the lack of predictive pre-clinical models is a burden. The principle differences between relevant innate and adaptive immune responses in humans and other species are reviewed. Especially, the extreme differences between the immune system of non-human primates and humans are cumbersome as non-human primates may not be predictive of the immune responses in humans, as opposed to the popular belief of regulatory agencies. Current insight is that although the technology is versatile major research efforts are required for identifying the mechanical, immunological, and physico-chemical requirements that alginate-based capsules should meet for successful human application.

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Pinpointing a selective sweep to the chimpanzee MHC class I region by comparative genomics

Cited by 46 publications

References 73 publications

Low MHC class II diversity in the Tasmanian devil (Sarcophilus harrisii)

Low MHC class II diversity in the Tasmanian devil (Sarcophilus harrisii)

Impact of Endogenous Intronic Retroviruses on Major Histocompatibility Complex Class II Diversity and Stability

Immunological and Technical Considerations in Application of Alginate-Based Microencapsulation Systems

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