Department of Anatomy, Howard University, Washington, DC 20053, USA.
Glycobiology. 2013 Apr;23(4):398-411. doi: 10.1093/glycob/cws218. Epub 2013 Jan 12.
Hyaluronan is a high-molecular-weight glycosaminoglycan (GAG) prominent in the extracellular matrix. Emerging relatively late in evolution, it may have evolved to evade immune recognition. Chondroitin is a more ancient GAG and a possible hyaluronan precursor. Epimerization of a 4-hydroxyl in N-acetylgalactosamine in chondroitin to N-acetylglucosamine of hyaluronan is the only structural difference other than chain length between these two polymers. The axial 4-hydroxyl group extends out perpendicular from the equatorial plane of N-acetylgalactosamine in chondroitin. We suspect that this hydroxyl is a prime target for immune recognition. Conversion of a thumbs-up hydroxyl group into a thumbs-down position in the plane of the sugar endows hyaluronan with the ability to avoid immune recognition. Chitin is another potential precursor to hyaluronan. But regardless whether of chondroitin or of chitin origin, an ancient chondroitinase enzyme sequence seems to have been commandeered to catalyze the cleavage of the new hyaluronan substrate. The evolution of six hyaluronidase-like sequences in the human genome from a single chondroitinase as found in Caenorhabditis elegans can now be traced. Confirming our previous predictions, two duplication events occurred, with three hyaluronidase-like sequences occurring in the genome of Ciona intestinalis (sea squirt), the earliest known chordate. This was probably followed by en masse duplication, with six such genes present in the genome of zebra fish onwards. These events occurred, however, much earlier than predicted. It is also apparent on an evolutionary time scale that in several species, this gene family is continuing to evolve.
透明质酸是一种高分子量糖胺聚糖（GAG），在细胞外基质中尤为突出。它在进化中出现较晚，可能是为了逃避免疫识别而进化的。软骨素是一种更古老的 GAG，可能是透明质酸的前体。在软骨素中，N-乙酰半乳糖胺的 4-羟基向 N-乙酰葡萄糖胺的差向异构化是这两种聚合物除链长外唯一的结构差异。在软骨素中，轴向 4-羟基垂直于 N-乙酰半乳糖胺的赤道平面伸出。我们怀疑这个羟基是免疫识别的主要目标。在糖的平面上将一个竖起大拇指的羟基转化为一个向下的位置，赋予透明质酸逃避免疫识别的能力。几丁质是透明质酸的另一个潜在前体。但无论是软骨素还是几丁质起源，似乎都有一种古老的软骨素酶序列被劫持来催化新的透明质酸底物的切割。现在可以追溯到人基因组中从秀丽隐杆线虫中发现的单一软骨素酶中进化而来的 6 个透明质酸酶样序列。证实了我们之前的预测，发生了两次复制事件，在海鞘（sea squirt）的基因组中出现了 3 个透明质酸酶样序列。随后可能发生了大规模的复制，斑马鱼及其后的基因组中都存在 6 个这样的基因。然而，这些事件发生的时间远比预测的要早。从进化时间尺度上也可以明显看出，在几个物种中，这个基因家族还在继续进化。
