Hosomichi Kazuyoshi, Shiina Takashi, Suzuki Shingo, Tanaka Masayuki, Shimizu Sayoko, Iwamoto Shigehisa, Hara Hiromi, Yoshida Yutaka, Kulski Jerzy K, Inoko Hidetoshi, Hanzawa Kei
Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1143, Japan.
BMC Genomics. 2006 Dec 21;7:322. doi: 10.1186/1471-2164-7-322.
The quail and chicken major histocompatibility complex (Mhc) genomic regions have a similar overall organization but differ markedly in that the quail has an expanded number of duplicated class I, class IIB, natural killer (NK)-receptor-like, lectin-like and BG genes. Therefore, the elucidation of genetic factors that contribute to the greater Mhc diversity in the quail would help to establish it as a model experimental animal in the investigation of avian Mhc associated diseases. AIMS AND APPROACHES: The main aim here was to characterize the genetic and genomic features of the transcribed major quail MhcIIB (CojaIIB) region that is located between the Tapasin and BRD2 genes, and to compare our findings to the available information for the chicken MhcIIB (BLB). We used four approaches in the study of the quail MhcIIB region, (1) haplotype analyses with polymorphic loci, (2) cloning and sequencing of the RT-PCR CojaIIB products from individuals with different haplotypes, (3) genomic sequencing of the CojaIIB region from the individuals with the different haplotypes, and (4) phylogenetic and duplication analysis to explain the variability of the region between the quail and the chicken.
Our results show that the Tapasin-BRD2 segment of the quail Mhc is highly variable in length and in gene transcription intensity and content. Haplotypic sequences were found to vary in length between 4 to 11 kb. Tapasin-BRD2 segments contain one or two major transcribed CojaIIBs that were probably generated by segmental duplications involving c-type lectin-like genes and NK receptor-like genes, gene fusions between two CojaIIBs and transpositions between the major and minor CojaIIB segments. The relative evolutionary speed for generating the MhcIIBs genomic structures from the ancestral BLB2 was estimated to be two times faster in the quail than in the chicken after their separation from a common ancestor. Four types of genomic rearrangement elements (GRE), composed of simple tandem repeats (STR), were identified in the MhcIIB genomic segment located between the Tapasin-BRD2 genes. The GREs have many more STR numbers in the quail than in the chicken that displays strong linkage disequilibrium.
This study suggests that the Mhc classIIB region has a flexible genomic structure generated by rearrangement elements and rapid SNP accumulation probably as a consequence of the quail adapting to environmental conditions and pathogens during its migratory history after its divergence from the chicken.
鹌鹑和鸡的主要组织相容性复合体(Mhc)基因组区域总体组织相似,但明显不同的是,鹌鹑中I类、IIB类、自然杀伤(NK)受体样、凝集素样和BG基因的重复数量有所增加。因此,阐明导致鹌鹑中Mhc多样性更高的遗传因素,将有助于将其确立为研究禽类Mhc相关疾病的实验动物模型。目的与方法:这里的主要目的是表征位于Tapasin和BRD2基因之间的转录鹌鹑主要MhcIIB(CojaIIB)区域的遗传和基因组特征,并将我们的发现与鸡MhcIIB(BLB)的现有信息进行比较。我们在鹌鹑MhcIIB区域的研究中使用了四种方法:(1)对多态性位点进行单倍型分析;(2)对不同单倍型个体的RT-PCR CojaIIB产物进行克隆和测序;(3)对不同单倍型个体的CojaIIB区域进行基因组测序;(4)进行系统发育和重复分析,以解释鹌鹑和鸡之间该区域的变异性。
我们的结果表明,鹌鹑Mhc的Tapasin - BRD2片段在长度、基因转录强度和含量方面高度可变。发现单倍型序列长度在4至11 kb之间变化。Tapasin - BRD2片段包含一个或两个主要转录的CojaIIB,可能是由涉及c型凝集素样基因和NK受体样基因的片段重复、两个CojaIIB之间的基因融合以及主要和次要CojaIIB片段之间的转座产生的。从共同祖先分离后,鹌鹑从祖先BLB2产生MhcIIB基因组结构的相对进化速度估计比鸡快两倍。在位于Tapasin - BRD2基因之间的MhcIIB基因组片段中,鉴定出由简单串联重复序列(STR)组成的四种类型的基因组重排元件(GRE)。鹌鹑中的GRE的STR数量比显示出强连锁不平衡的鸡中的STR数量多得多。
本研究表明,Mhc IIB区域具有由重排元件产生的灵活基因组结构以及快速的SNP积累,这可能是鹌鹑在与鸡分化后的迁徙历史中适应环境条件和病原体的结果。