Brancaccio Andrea, Adams Josephine C
Istituto di Chimica del Riconoscimento Molecolare, CNR, Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy.
School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK.
BMC Res Notes. 2017 Jan 3;10(1):19. doi: 10.1186/s13104-016-2322-x.
Dystroglycan (DG) is an adhesion receptor complex composed of two non-covalently associated subunits, transcribed from a single gene. The extracellular α-DG is highly and heterogeneously glycosylated and binds with high affinity to laminins, and the transmembrane β-DG binds intracellular dystrophin. Multiple cellular functions have been proposed for DG, notwithstanding that its role in skeletal muscle appears central as demonstrated by both primary and secondary severe muscular dystrophic phenotypes collectively known as dystroglycanopathies. We recently analysed the molecular phylogeny of the DG core protein and identified the α/β interface, transmembrane and cytoplasmic domains of β-DG as the most conserved region. It was also identified that the IG2_MAT_NU region has been independently duplicated in multiple lineages.
To understand the evolution of dystroglycan in more depth, we investigated dystroglycan gene structure in 35 species representative of the phyla in which dystroglycan has been identified (i.e., all metazoan phyla except Ctenophora). The gene structure of three exons and two introns is remarkably conserved. However, additional lineage-specific introns were identified, which interrupt the coding sequence at distinct points, were identified in multiple metazoan groups, most prominently in ecdysozoans.
A coding DNA sequence (CDS) intron that interrupts the encoding of the IG1 domain is universally conserved and this intron is longer in gnathostomes (jawed vertebrates) than in other metazoans. Lineage-specific gain of additional introns has occurred notably in ecdysozoans, where multiple introns interrupt the large 3' exon. More limited intron gain has also occurred in placozoa, cnidarians, urochordates and the DG paralogues of lamprey and teleost fish.
肌营养不良聚糖（DG）是一种由两个非共价结合亚基组成的黏附受体复合物，由单一基因转录而来。细胞外的α-DG高度且异质性糖基化，能与层粘连蛋白高亲和力结合，而跨膜的β-DG则与细胞内的肌营养不良蛋白结合。尽管DG在骨骼肌中的作用似乎是核心的，这一点在原发性和继发性严重肌肉营养不良表型（统称为肌营养不良聚糖病）中都得到了证实，但人们还是提出了DG的多种细胞功能。我们最近分析了DG核心蛋白的分子系统发育，并确定β-DG的α/β界面、跨膜和细胞质结构域是最保守的区域。还发现IG2_MAT_NU区域在多个谱系中独立重复。
为了更深入地了解肌营养不良聚糖的进化，我们研究了35种代表已鉴定出肌营养不良聚糖的门（即除栉水母动物门外的所有后生动物门）的物种中的肌营养不良聚糖基因结构。三个外显子和两个内含子的基因结构非常保守。然而，在多个后生动物类群中，尤其是在蜕皮动物中，发现了额外的谱系特异性内含子，这些内含子在不同位置中断了编码序列。
一个中断IG1结构域编码的编码DNA序列（CDS）内含子普遍保守，并且在有颌脊椎动物中比在其他后生动物中更长。额外内含子的谱系特异性获得在蜕皮动物中尤为显著，其中多个内含子中断了大的3'外显子。在扁盘动物、刺胞动物、尾索动物以及七鳃鳗和硬骨鱼的DG旁系同源物中也发生了更有限的内含子获得。
