Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia.
BMC Genomics. 2011 Aug 19;12:421. doi: 10.1186/1471-2164-12-421.
The major histocompatibility complex (MHC) is a group of genes with a variety of roles in the innate and adaptive immune responses. MHC genes form a genetically linked cluster in eutherian mammals, an organization that is thought to confer functional and evolutionary advantages to the immune system. The tammar wallaby (Macropus eugenii), an Australian marsupial, provides a unique model for understanding MHC gene evolution, as many of its antigen presenting genes are not linked to the MHC, but are scattered around the genome.
Here we describe the 'core' tammar wallaby MHC region on chromosome 2q by ordering and sequencing 33 BAC clones, covering over 4.5 MB and containing 129 genes. When compared to the MHC region of the South American opossum, eutherian mammals and non-mammals, the wallaby MHC has a novel gene organization. The wallaby has undergone an expansion of MHC class II genes, which are separated into two clusters by the class III genes. The antigen processing genes have undergone duplication, resulting in two copies of TAP1 and three copies of TAP2. Notably, Kangaroo Endogenous Retroviral Elements are present within the region and may have contributed to the genomic instability.
The wallaby MHC has been extensively remodeled since the American and Australian marsupials last shared a common ancestor. The instability is characterized by the movement of antigen presenting genes away from the core MHC, most likely via the presence and activity of retroviral elements. We propose that the movement of class II genes away from the ancestral class II region has allowed this gene family to expand and diversify in the wallaby. The duplication of TAP genes in the wallaby MHC makes this species a unique model organism for studying the relationship between MHC gene organization and function.
主要组织相容性复合体（MHC）是一组在先天和适应性免疫反应中具有多种作用的基因。MHC 基因在真兽类哺乳动物中形成一个遗传连锁簇，这种组织被认为赋予了免疫系统功能和进化优势。塔马尔袋鼠（Macropus eugenii），一种澳大利亚有袋动物，为理解 MHC 基因进化提供了一个独特的模型，因为其许多抗原呈递基因与 MHC 没有联系，而是散布在基因组周围。
在这里，我们通过对 33 个 BAC 克隆进行排序和测序，描述了染色体 2q 上的“核心”塔马尔袋鼠 MHC 区域，该区域覆盖了超过 4.5MB 并包含 129 个基因。与南美的负鼠、真兽类哺乳动物和非哺乳动物的 MHC 区域相比，袋獾 MHC 具有新颖的基因组织。袋獾 MHC 类 II 基因发生了扩张，这些基因被 III 类基因分隔成两个簇。抗原加工基因发生了复制，导致 TAP1 有两个拷贝，TAP2 有三个拷贝。值得注意的是，袋鼠内源性逆转录病毒元件存在于该区域，可能导致了基因组的不稳定性。
自美洲和澳大利亚有袋动物最后一次拥有共同祖先以来，袋獾 MHC 经历了广泛的重塑。不稳定性的特征是抗原呈递基因从核心 MHC 中转移，最可能是通过逆转录元件的存在和活性。我们提出，II 类基因从祖先 II 类区域的转移使这个基因家族在袋獾中得以扩张和多样化。袋獾 MHC 中 TAP 基因的复制使该物种成为研究 MHC 基因组织与功能之间关系的独特模式生物。
