School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales 2006, Australia.
Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, University of Sydney, Sydney, New South Wales 2006, Australia.
Genome Biol Evol. 2024 Aug 5;16(8). doi: 10.1093/gbe/evae156.
The major histocompatibility complex (MHC) plays a vital role in the vertebrate immune system due to its role in infection, disease and autoimmunity, or recognition of "self". The marsupial MHC class II genes show divergence from eutherian MHC class II genes and are a unique taxon of therian mammals that give birth to altricial and immunologically naive young providing an opportune study system for investigating evolution of the immune system. Additionally, the MHC in marsupials has been implicated in disease associations, including susceptibility to Chlamydia pecorum infection in koalas. Due to the complexity of the gene family, automated annotation is not possible so here we manually annotate 384 class II MHC genes in 29 marsupial species. We find losses of key components of the marsupial MHC repertoire in the Dasyuromorphia order and the Pseudochiridae family. We perform PGLS analysis to show the gene losses we find are true gene losses and not artifacts of unresolved genome assembly. We investigate the associations between the number of loci and life history traits, including lifespan and reproductive output in lineages of marsupials and hypothesize that gene loss may be linked to the energetic cost and tradeoffs associated with pregnancy and reproduction. We found support for litter size being a significant predictor of the number of DBA and DBB loci, indicating a tradeoff between the energetic requirements of immunity and reproduction. Additionally, we highlight the increased susceptibility of Dasyuridae species to neoplasia and a potential link to MHC gene loss. Finally, these annotations provide a valuable resource to the immunogenetics research community to move forward and further investigate diversity in MHC genes in marsupials.
主要组织相容性复合体 (MHC) 在脊椎动物免疫系统中起着至关重要的作用，因为它在感染、疾病和自身免疫或识别“自我”方面发挥作用。有袋类 MHC 类 II 基因与真兽类 MHC 类 II 基因有分歧，是真兽类哺乳动物中一个独特的分类群，它们生育出晚熟且免疫幼稚的幼崽，为研究免疫系统的进化提供了一个很好的研究系统。此外，MHC 在有袋类动物中与疾病相关联，包括考拉对衣原体感染的易感性。由于基因家族的复杂性，自动化注释是不可能的，因此在这里我们手动注释了 29 种有袋动物中的 384 个 II 类 MHC 基因。我们发现袋鼬目和袋鼹科的 MHC 库关键组成部分丢失。我们进行 PGLS 分析表明，我们发现的基因丢失是真正的基因丢失，而不是未解决的基因组组装的假象。我们调查了基因座数量与生活史特征（包括寿命和繁殖输出）之间的关联，这些特征存在于有袋动物的谱系中，并假设基因丢失可能与与怀孕和繁殖相关的能量成本和权衡有关。我们发现，胎数与 DBA 和 DBB 基因座数量之间存在显著相关性，表明免疫力和繁殖之间存在能量需求的权衡。此外，我们还强调了袋鼬科物种对肿瘤形成的易感性增加，并可能与 MHC 基因丢失有关。最后，这些注释为免疫遗传学研究界提供了有价值的资源，以推进并进一步研究有袋动物 MHC 基因的多样性。
