Bekpen Cemalettin, Hunn Julia P, Rohde Christoph, Parvanova Iana, Guethlein Libby, Dunn Diane M, Glowalla Eva, Leptin Maria, Howard Jonathan C
Institute for Genetics, University of Cologne, Zülpicher Strasse 47, 50674 Cologne, Germany.
Genome Biol. 2005;6(11):R92. doi: 10.1186/gb-2005-6-11-r92. Epub 2005 Oct 31.
Members of the p47 (immunity-related GTPases (IRG) family) GTPases are essential, interferon-inducible resistance factors in mice that are active against a broad spectrum of important intracellular pathogens. Surprisingly, there are no reports of p47 function in humans.
Here we show that the p47 GTPases are represented by 23 genes in the mouse, whereas humans have only a single full-length p47 GTPase and an expressed, truncated presumed pseudo-gene. The human full-length gene is orthologous to an isolated mouse p47 GTPase that carries no interferon-inducible elements in the promoter of either species and is expressed constitutively in the mature testis of both species. Thus, there is no evidence for a p47 GTPase-based resistance system in humans. Dogs have several interferon-inducible p47s, and so the primate lineage that led to humans appears to have lost an ancient function. Multiple p47 GTPases are also present in the zebrafish, but there is only a tandem p47 gene pair in pufferfish.
Mice and humans must deploy their immune resources against vacuolar pathogens in radically different ways. This carries significant implications for the use of the mouse as a model of human infectious disease. The absence of the p47 resistance system in humans suggests that possession of this resistance system carries significant costs that, in the primate lineage that led to humans, are not outweighed by the benefits. The origin of the vertebrate p47 system is obscure.
p47(免疫相关GTP酶(IRG)家族)GTP酶家族成员是小鼠体内至关重要的、可被干扰素诱导的抗性因子,对多种重要的细胞内病原体具有活性。令人惊讶的是,目前尚无关于p47在人类中功能的报道。
我们发现,p47 GTP酶在小鼠中由23个基因代表,而人类仅有一个全长p47 GTP酶和一个表达的、截短的假定假基因。人类全长基因与一个分离的小鼠p47 GTP酶直系同源,这两个物种的该基因启动子中均无干扰素诱导元件,且在两个物种的成熟睾丸中均组成性表达。因此,没有证据表明人类存在基于p47 GTP酶的抗性系统。狗有几种可被干扰素诱导的p47,所以导致人类的灵长类谱系似乎失去了一种古老的功能。斑马鱼中也存在多个p47 GTP酶,但河豚中只有一对串联的p47基因。
小鼠和人类必定以截然不同的方式调配其免疫资源来对抗液泡病原体。这对将小鼠用作人类传染病模型具有重大意义。人类缺乏p47抗性系统表明,拥有这种抗性系统会带来巨大成本,在导致人类的灵长类谱系中,这些成本并未被益处所抵消。脊椎动物p47系统的起源尚不清楚。