Molecular Signatures of Adaptation: MHC Evolution and Natural Selection in European Rabbits
type: CreativeWork
description: The Major Histocompatibility Complex (MHC) is a multi-gene family, covering a genomically complex region that plays a pivotal role in immune surveillance and pathogen recognition. Within this region, only a subset of MHC class I (MHC-I) genes encodes classical molecules that present peptides to CD8+ T cells. These molecules exhibit extraordinary genetic polymorphism, particularly in their peptide- binding domains, enabling them to bind a diverse array of pathogen-derived peptides and initiate targeted immune responses. While MHC-I genes evolve rapidly under pathogen pressure, their complex genomic architecture — characterised by gene duplication, gene conversion, and strong linkage disequilibrium — poses significant challenges for tracking evolutionary changes in natural populations. The myxomatosis pandemic in European rabbits (Oryctolagus cuniculus) provides an unprecedented opportunity to examine MHC-I evolution under intense viral selection. Following the release of myxoma virus as a biological control in 1950s in Australia, France and the United Kingdom, host and virus underwent rapid coevolution, with viral virulence declining and host resistance increasing dramatically within years. Although genome-wide analyses identified the MHC-I region as a target of selection during the pandemic, the specific genetic changes underlying resistance remained unknown. This thesis presents a comprehensive characterisation of MHC class I genes in Eu- ropean rabbits. Using PacBio long-read transcriptome sequencing from 68 modern rabbits, we identified and manually annotated 9 MHC-I paralogs on chromosome 12, named from Orcu-U1 to Orcu-U9. From these paralogs, 79 distinct alleles were identified, substantially improving our understanding of the MHC-I region in rabbits. Among these genes, Orcu-U1 and Orcu-U2 showed characteristics of classical MHC-I molecules — conserved residues for peptide presentation, high level of polymorphism, and wide and high tissue expression. To track M…
abstract: The Major Histocompatibility Complex (MHC) is a multi-gene family, covering a genomically complex region that plays a pivotal role in immune surveillance and pathogen recognition. Within this region, only a subset of MHC class I (MHC-I) genes encodes classical molecules that present peptides to CD8+ T cells. These molecules exhibit extraordinary genetic polymorphism, particularly in their peptide- binding domains, enabling them to bind a diverse array of pathogen-derived peptides and initiate targeted immune responses. While MHC-I genes evolve rapidly under pathogen pressure, their complex genomic architecture — characterised by gene duplication, gene conversion, and strong linkage disequilibrium — poses significant challenges for tracking evolutionary changes in natural populations. The myxomatosis pandemic in European rabbits (Oryctolagus cuniculus) provides an unprecedented opportunity to examine MHC-I evolution under intense viral selection. Following the release of myxoma virus as a biological control in 1950s in Australia, France and the United Kingdom, host and virus underwent rapid coevolution, with viral virulence declining and host resistance increasing dramatically within years. Although genome-wide analyses identified the MHC-I region as a target of selection during the pandemic, the specific genetic changes underlying resistance remained unknown. This thesis presents a comprehensive characterisation of MHC class I genes in Eu- ropean rabbits. Using PacBio long-read transcriptome sequencing from 68 modern rabbits, we identified and manually annotated 9 MHC-I paralogs on chromosome 12, named from Orcu-U1 to Orcu-U9. From these paralogs, 79 distinct alleles were identified, substantially improving our understanding of the MHC-I region in rabbits. Among these genes, Orcu-U1 and Orcu-U2 showed characteristics of classical MHC-I molecules — conserved residues for peptide presentation, high level of polymorphism, and wide and high tissue expression. To track M…
author: Zhang, Yexin
keywords: European Rabbits, Evolutionary Genetics, MHC-I, Natural Selection
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/88e3c1f5-bc34-499d-a567-31e386253170/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2025-04-03
date modified: 2026-07-22T22:24:25Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.120035