Chitinase family GH18: evolutionary insights from the genomic history of a diverse protein family
Chitinase family GH18: evolutionary insights from the genomic history of a diverse protein family
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DOI：
10.1186/1471-2148-7-96
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发表时间：
2007-06-26
影响因子：
3.4
通讯作者：
Aronson, Nathan N., Jr.
中科院分区：
文献类型：
--
作者：
Funkhouser, Jane D.;Aronson, Nathan N., Jr.
背景：几丁质酶（EC.3.2.1.14）水解几丁质中的-1,4键，几丁质是一种丰富的n -乙酰- β -氨基葡萄糖多糖，是昆虫外骨骼和真菌细胞壁等保护性生物基质的结构成分。几丁质酶的糖苷水解酶18 （GH18）家族是一个古老的基因家族，广泛表达于古生物、原核生物和真核生物中。哺乳动物无法合成甲壳素或将其作为一种营养物质进行代谢，但人类基因组编码了8个GH18家族成员。一些GH18蛋白缺乏必要的催化谷氨酸，可能起凝集素而不是酶的作用。本研究使用比较基因组分析来解决GH18多蛋白家族的进化史，从早期真核生物到哺乳动物，以了解塑造人类基因组中几丁质酶相关蛋白含量的力量。结果：根据进化的出生和死亡模型，基因复制和丢失是GH18家族进化史的一个特征。现在的人类家族可能起源于双边扩张时期的古老基因。550米娅)。该家族在几丁质原口动物C. elegans和D. melanogaster中扩大，在早期后口动物中随着几丁质合成的消失而减少，在鸟/哺乳动物分裂后，在后期后口动物中随着基因数量的显著增加而再次扩大。结论：这项对动物GH18蛋白的全面基因组研究揭示了GH18家族的三个主要系统发育群：几丁质酶/几丁质酶和稳定蛋白-1相互作用的几丁质。只有几丁质酶/壳聚糖组与后口动物后期的扩张有关。发现人类GH18基因家族与1号染色体上的人类主要组织相容性复合体旁拉贡密切相关，以及GH18几丁质酶活性最近与Th2细胞炎症的关联，表明其晚期扩增可能与早期脊椎动物历史中先天免疫和适应性免疫的新界面有关。
Background: Chitinases (EC.3.2.1.14) hydrolyze the beta-1,4-linkages in chitin, an abundant N-acety-beta-glucosamine polysaccharide that is a structural component of protective biological matrices such as insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 (GH18) family of chitinases is an ancient gene family widely expressed in archea, prokaryotes and eukaryotes. Mammals are not known to synthesize chitin or metabolize it as a nutrient, yet the human genome encodes eight GH18 family members. Some GH18 proteins lack an essential catalytic glutamic acid and are likely to act as lectins rather than as enzymes. This study used comparative genomic analysis to address the evolutionary history of the GH18 multiprotein family, from early eukaryotes to mammals, in an effort to understand the forces that shaped the human genome content of chitinase related proteins. Results: Gene duplication and loss according to a birth-and-death model of evolution is a feature of the evolutionary history of the GH18 family. The current human family likely originated from ancient genes present at the time of the bilaterian expansion (approx. 550 mya). The family expanded in the chitinous protostomes C. elegans and D. melanogaster, declined in early deuterostomes as chitin synthesis disappeared, and expanded again in late deuterostomes with a significant increase in gene number after the avian/mammalian split. Conclusion: This comprehensive genomic study of animal GH18 proteins reveals three major phylogenetic groups in the family: chitobiases, chitinases/chitolectins, and stabilin-1 interacting chitolectins. Only the chitinase/chitolectin group is associated with expansion in late deuterostomes. Finding that the human GH18 gene family is closely linked to the human major histocompatibility complex paralogon on chromosome 1, together with the recent association of GH18 chitinase activity with Th2 cell inflammation, suggests that its late expansion could be related to an emerging interface of innate and adaptive immunity during early vertebrate history.