Brunet Frédéric G, Fraser Fiona W, Binder Marley J, Smith Adam D, Kintakas Christopher, Dancevic Carolyn M, Ward Alister C, McCulloch Daniel R
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 46, allée d'Italie, 69364, Lyon cedex 07, France.
School of Medicine, Deakin University, Geelong, VIC, 3216, Australia.
BMC Evol Biol. 2015 Feb 15;15:22. doi: 10.1186/s12862-015-0281-9.
The A Disintegrin-like and Metalloproteinase domain with Thrombospondin-1 motifs (ADAMTS) enzymes comprise 19 mammalian zinc-dependent metalloproteinases (metzincins) with homologues in a wide range of invertebrates. ADAMTS enzymes have a broad range of functions in development and diseases due to their extracellular matrix remodelling activity. Here, we report a detailed characterisation of their evolutionary conservation across vertebrates.
Using bioinformatics complemented with de novo sequencing, gene sequences for ADAMTS enzymes were obtained from a variety of organisms. Detailed evolutionary analyses revealed a high level of conservation across vertebrates with evidence of ADAMTS gene expansion during two rounds of whole genome duplication (WGD) in vertebrates, while tandem duplication events and gene loss were also apparent. However, the additional round of teleost-specific WGD did not have a significant effect on ADAMTS gene family members suggesting their conserved roles have remained constant in teleost fish. Quantitative reverse-transcriptase polymerase chain reaction analysis revealed dynamic expression of adamts genes throughout zebrafish embryonic development reflecting the key conserved roles they play in vertebrate embryogenesis. Notably, several adamts mRNAs were maternally expressed with a dramatic increase in mRNA levels coinciding with zygotic expression and organogenesis. Broad adamts mRNA expression was also demonstrated in several adult organs indicating potential roles in adult homeostasis.
Our data highlight the evolution of the ADAMTS gene family through duplication processes across metazoans supplemented by a burst of amplification through vertebrate WGD events. It also strongly posits the zebrafish as a potential model species to further elucidate the function of ADAMTS enzymes during vertebrate development.
含血小板反应蛋白-1基序的解整合素样金属蛋白酶（ADAMTS）家族包含19种哺乳动物锌依赖性金属蛋白酶（金属锌蛋白酶），在多种无脊椎动物中也有同源物。由于其细胞外基质重塑活性，ADAMTS酶在发育和疾病中具有广泛的功能。在此，我们报告了它们在脊椎动物中的详细进化保守特征。
通过生物信息学结合从头测序，从多种生物体中获得了ADAMTS酶的基因序列。详细的进化分析显示，脊椎动物中具有高度的保守性，有证据表明在脊椎动物两轮全基因组复制（WGD）期间ADAMTS基因发生了扩增，同时串联重复事件和基因丢失也很明显。然而，硬骨鱼特有的另一轮WGD对ADAMTS基因家族成员没有显著影响，这表明它们在硬骨鱼中的保守作用保持不变。定量逆转录聚合酶链反应分析显示，在斑马鱼胚胎发育过程中，adamts基因呈动态表达，反映了它们在脊椎动物胚胎发生中所起的关键保守作用。值得注意的是，几种adamts mRNA是母源表达的，其mRNA水平在合子表达和器官发生时显著增加。在几个成体器官中也检测到了广泛的adamts mRNA表达，表明它们在成体稳态中可能发挥作用。
我们的数据突出了ADAMTS基因家族通过后生动物的复制过程以及脊椎动物WGD事件引发的扩增而发生的进化。这也有力地表明斑马鱼是进一步阐明ADAMTS酶在脊椎动物发育过程中功能的潜在模式物种。
