Gene-Gene Interaction and Functional Impact of Polymorphisms on Innate Immune Genes in Controlling Plasmodium falciparum Blood Infection Level

Basu, Madhumita; Das, Tania; Ghosh, Alip; Majumder, Subhadipa; Maji, Ardhendu Kumar; Kanjilal, Sumana Datta; Mukhopadhyay, Indranil; Roychowdhury, Susanta; Banerjee, Soma; Sengupta, Sanghamitra

doi:10.1371/journal.pone.0046441

Cited by 14 publications

(14 citation statements)

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“…Similar losses in diversity in immune defence genes associated with bottleneck events have been reported in other endangered vertebrates (Eimes et al 2011;Jamieson 2011;Basu et al 2012;Zhu et al 2013). The majority of heterozygous Seychelles warbler individuals have the rare variants observed, which suggests there may be a selective advantage with heterozygosity.…”

Section: Discussionsupporting

confidence: 71%

Avian β-defensin variation in bottlenecked populations: the Seychelles warbler and other congeners

et al. 2016

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b-defensins are important components of the vertebrate innate immune system responsible for encoding a variety of anti-microbial peptides. Pathogen-mediated selection is thought to act on immune genes and potentially maintain allelic variation in the face of genetic drift. The Seychelles warbler, Acrocephalus sechellensis, is an endemic passerine that underwent a recent bottleneck in its last remaining population, resulting in a considerable reduction in genome-wide variation. We genotyped avian b-defensin (AvBD) genes in contemporary (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008) and museum samples of the Seychelles warbler to investigate whether immunogenetic variation was lost through this bottleneck, and examined AvBD variation across four other Acrocephalus species with varying demographic histories. No variation was detected at four of the six AvBD loci screened in the post-bottleneck population of Seychelles warbler, but two silent nucleotide polymorphisms were identified at AvBD8 and one potentially functional amino-acid variation was observed at AvBD11. Variation in the Seychelles warbler was significantly lower than in the mainland migratory congeneric species investigated, but it similar to that found in other bottlenecked species. In addition, screening AvBD7 in 15 museum specimens of Seychelles warblers sampled prior to the bottleneck revealed that this locus possessed two alleles previously, compared to the single allele in the contemporary population. Overall, the results show that little AvBD variation remains in the Seychelles warbler, probably as a result of having low AvBD diversity historically rather than the loss of variation due to drift associated with past demographic history. Given the limited pathogen fauna, this lack of variation at the AvBD loci may currently not pose a problem for this isolate population of Seychelles warblers, but it may be detrimental to the species' long-term survival if new pathogens reach the population in the future.

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Section: Discussionsupporting

confidence: 71%

Avian β-defensin variation in bottlenecked populations: the Seychelles warbler and other congeners

et al. 2016

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“…If TLRs are involved in a co‐evolutionary arms race with pathogens, it is likely that balancing selection operates at these genes. This idea is also supported by the direct links that have been made between in vitro nucleotide variation at these genes with differential disease outcome (Basu et al ., ; Netea et al ., ).…”

Section: Introductionmentioning

confidence: 98%

Toll‐like receptor variation in the bottlenecked population of the Seychelles warbler: computer simulations see the ‘ghost of selection past’ and quantify the ‘drift debt’

Gilroy

Phillips

Richardson

et al. 2017

J of Evolutionary Biology

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Balancing selection can maintain immunogenetic variation within host populations, but detecting its signal in a postbottlenecked population is challenging due to the potentially overriding effects of drift. Toll-like receptor genes (TLRs) play a fundamental role in vertebrate immune defence and are predicted to be under balancing selection. We previously characterized variation at TLR loci in the Seychelles warbler (Acrocephalus sechellensis), an endemic passerine that has undergone a historical bottleneck. Five of seven TLR loci were polymorphic, which is in sharp contrast to the low genomewide variation observed. However, standard population genetic statistical methods failed to detect a contemporary signature of selection at any TLR locus. We examined whether the observed TLR polymorphism could be explained by neutral evolution, simulating the population's demography in the software DIYABC. This showed that the posterior distributions of mutation rates had to be unrealistically high to explain the observed genetic variation. We then conducted simulations with an agent-based model using typical values for the mutation rate, which indicated that weak balancing selection has acted on the three TLR genes. The model was able to detect evidence of past selection elevating TLR polymorphism in the prebottleneck populations, but was unable to discern any effects of balancing selection in the contemporary population. Our results show drift is the overriding evolutionary force that has shaped TLR variation in the contemporary Seychelles warbler population, and the observed TLR polymorphisms might be merely the 'ghost of selection past'. Forecast models predict immunogenetic variation in this species will continue to be eroded in the absence of contemporary balancing selection. Such 'drift debt' occurs when a gene pool has not yet reached its new equilibrium level of polymorphism, and this loss could be an important threat to many recently bottlenecked populations.

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confidence: 99%

“…Modeling with MFOLD indicates that the C allele of this polymorphism prevents the binding of several transcription factors by altering the accessibility of the DNA (Basu et al 2012). In studies of malaria, this SNP has been associated with increased parasitemia, heightened severity of disease, and incidence of cerebral involvement (Basu et al 2012; Hananantachai et al 2007; Sinha et al 2008). Case studies have found the minor allele G of this SNP to be associated with Crohn’s disease, asthma, decreased immunity after natural infection or vaccination against measles, and cancer-associated mortality (Dhiman et al 2008; Gallicchio et al 2008; Puthothu et al 2009; Sanchez et al 2009).…”

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Structure of tumor necrosis factor-alpha haploblocks in European populations

et al. 2013

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DNA variants in the tumor necrosis factor-α (TNF) and linked lymphotoxin-α genes, and specific alleles of the highly polymorphic human leukocyte antigen B (HLA-B) gene have been implicated in a plethora of immune and infectious diseases. However, the tight linkage disequilibrium characterizing the central region of the human major histocompatibility complex (MHC) containing these gene loci has made difficult the unequivocal interpretation of genetic association data. To alleviate these difficulties and facilitate the design of more focused follow-up studies, we investigated the structure and distribution of HLA-B-specific MHC haplotypes reconstructed in a European population from unphased genotypes at a set of 25 single nucleotide polymorphism sites spanning a 66 kilobase-long region across TNF. Consistent with the published data, we found limited genetic diversity across the so-called TNF block, with the emergence of seven common MHC haplotypes, termed TNF block super-haplotypes. We also found that the ancestral haplotype 8.1 shares a TNF block haplotype with HLA-B*4402. HLA-B*5701, a known protective allele in HIV-1 pathogenesis, occurred in a unique TNF block haplotype.

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Gene-Gene Interaction and Functional Impact of Polymorphisms on Innate Immune Genes in Controlling Plasmodium falciparum Blood Infection Level

Cited by 14 publications

References 124 publications

Avian β-defensin variation in bottlenecked populations: the Seychelles warbler and other congeners

Avian β-defensin variation in bottlenecked populations: the Seychelles warbler and other congeners

Toll‐like receptor variation in the bottlenecked population of the Seychelles warbler: computer simulations see the ‘ghost of selection past’ and quantify the ‘drift debt’

Structure of tumor necrosis factor-alpha haploblocks in European populations

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