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Avian major histocompatibility complex copy number variation is associated with helminth richness.

ABSTRACT: Genes of the major histocompatibility complex (MHC) play a key role in the adaptive immunity of vertebrates, as they encode receptors responsible for antigen recognition. Evolutionary history of the MHC proceeded through numerous gene duplications, which increase the spectrum of pathogens recognized by individuals. Although pathogen-mediated selection is believed to be a primary driver of MHC expansion over evolutionary times, empirical evidence for this association is virtually lacking. Here, we used an extensive dataset on MHC class II copy number variation in non-passerine birds to test for an evolutionary correlation with helminth parasite richness. As expected, our phylogenetically-informed modelling revealed a positive association between MHC copy number and total helminth richness, even after controlling for a broad spectrum of ecological and life-history traits. Thus, total helminth richness appears to be the most important correlate of MHC copy number, supporting a leading role of pathogen-mediated selection in the evolution of MHC in birds. Our results provide some of the first, although correlative, evidence linking parasitism to interspecific variation in MHC copy number among birds.

SUBMITTER: Minias P

PROVIDER: S-EPMC7423054 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Avian major histocompatibility complex copy number variation is associated with helminth richness.

Minias Piotr P Gutiérrez Jorge S JS Dunn Peter O PO

Biology letters 20200708 7

Genes of the major histocompatibility complex (MHC) play a key role in the adaptive immunity of vertebrates, as they encode receptors responsible for antigen recognition. Evolutionary history of the MHC proceeded through numerous gene duplications, which increase the spectrum of pathogens recognized by individuals. Although pathogen-mediated selection is believed to be a primary driver of MHC expansion over evolutionary times, empirical evidence for this association is virtually lacking. Here, w ...[more]

PMID: 32634375

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Project description:Genetic markers for distant metastatic disease in patients with colorectal cancer (CRC) are not well defined. Identification of genetic alterations associated with metastatic CRC could help to guide systemic and local treatment strategies. We evaluated the association of tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) copy number variation (CNV) with distant metastatic disease in patients with CRC using The Cancer Genome Atlas (TCGA).Genetic sequencing data and clinical characteristics were obtained from TCGA for all available patients with CRC. There were 515 CRC patient samples with CNV and clinical outcome data, including a subset of 144 rectal adenocarcinoma patient samples. Using the TCGA CRC dataset, CNV of TNFRSF10C was evaluated for association with distant metastatic disease (M1 vs. M0). Multivariate logistic regression analysis with odds ratio (OR) using a 95% confidence interval (CI) was performed adjusting for age, T stage, N stage, adjuvant chemotherapy, gender, microsatellite instability (MSI), location, and surgical margin status.TNFRSF10C CNV in patients with CRC was associated with distant metastatic disease [OR 4.81 (95% CI, 2.13-10.85) P<0.001] and positive lymph nodes [OR 18.83 (95% CI, 8.42-42.09)]; P<0.001) but not MSI (OR P=0.799). On multivariate analysis, after adjusting for pathologic T stage, N stage, adjuvant chemotherapy, gender, and MSI, TNFRSF10C CNV remained significantly associated with distant metastatic disease (OR P=0.018). Subset analysis revealed that TNFRSF10C CNV was also significantly associated with distant metastatic disease in patients with rectal adenocarcinoma (OR P=0.016).TNFRSF10C CNV in patients with CRC is associated with distant metastatic disease. With further validation, such genetic profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive local therapies in patients with CRC, including radiation therapy for rectal adenocarcinoma.

Dataset Information

Avian major histocompatibility complex copy number variation is associated with helminth richness.

Publications

Avian major histocompatibility complex copy number variation is associated with helminth richness.

Similar Datasets

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