Animal Genomics Laboratory, Animal Biotechnology Centre, National Dairy Research Institute, Karnal, Haryana, 132001, India.
BMC Evol Biol. 2019 Jan 17;19(1):26. doi: 10.1186/s12862-018-1334-7.
ALRs (AIM2-like Receptors) are germline encoded PRRs that belong to PYHIN gene family of cytokines, which are having signature N-terminal PYD (Pyrin, PAAD or DAPIN) domain and C-terminal HIN-200 (hematopoietic, interferon-inducible nuclear protein with 200 amino acid repeat) domain joined by a linker region. The positively charged HIN-200 domain senses and binds with negatively charged phosphate groups of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) purely through electrostatic attractions. On the other hand, PYD domain interacts homotypically with a PYD domain of other mediators to pass the signals to effector molecules downwards the pathways for inflammatory responses. There is remarkable inter-specific diversity in the numbers of functional PYHIN genes e.g. one in cow, five in human, thirteen in mice etc., while there is a unique loss of PYHIN genes in the bat genomes which was revealed by Ahn et al. (2016) by studying genomes of ten different bat species belonging to sub-orders yinpterochiroptera and yangochiroptera. The conflicts between host and pathogen interfaces are compared with "Red queen's arms race" which is also described as binding seeking dynamics and binding avoidance dynamics. As a result of this never-ending rivalry, eukaryotes developed PRRs as antiviral mechanism while viruses developed counter mechanisms to evade host immune defense. The PYHIN receptors are directly engaged with pathogenic molecules, so these should have evolved under the influence of selection pressures. In the current study, we investigated the nature of selection pressure on different domain types of IFI16-like (IFI16-L) PYHIN genes in ruminants.
Three transcript variants of the IFI16-like gene were found in PBMCs of ruminant animals-water buffalo, zebu cattle, goat, and sheep. The IFI16-like gene has one N-terminal PYD domain and one C-terminal HIN-200 domain, separated by an inter-domain linker region. HIN domain and inter-domain region are positively selected while the PYD domain is under the influence of purifying selection.
Herein, we conclude that the nature of selection pressure varies on different parts (PYD domain, HIN domain, and inter-domain linker region) of IFI16-like PYHIN genes in the ruminants. This data can be useful to predict the molecular determinants of pathogen interactions.
ALRs（AIM2 样受体）是种系编码的 PRR，属于 PYHIN 细胞因子家族，其特征为 N 端 PYD（吡嗪酰胺酶、PAAD 或 DAPIN）结构域和 C 端 HIN-200（具有 200 个氨基酸重复的造血、干扰素诱导核蛋白）结构域，由连接区连接。带正电荷的 HIN-200 结构域通过静电吸引作用感应并结合单链 DNA（ssDNA）和双链 DNA（dsDNA）的负电荷磷酸基团。另一方面，PYD 结构域与其他介质的 PYD 结构域相互作用，将信号传递给向下游炎症反应途径的效应分子。在不同种属中，PYHIN 基因的数量存在显著的多样性，例如牛有一个，人有五个，鼠有十三个等，而蝙蝠基因组中存在独特的 PYHIN 基因缺失，这是由 Ahn 等人在研究属于翼手目亚目 yinpterochiroptera 和 yangochiroptera 的十种不同蝙蝠物种的基因组时揭示的（2016 年）。宿主与病原体界面之间的冲突与“红皇后的军备竞赛”相比较，这也被描述为结合寻求动力学和结合避免动力学。由于这种永无止境的竞争，真核生物进化出了抗病毒机制的 PRR，而病毒则进化出了逃避宿主免疫防御的机制。PYHIN 受体直接与致病性分子结合，因此这些受体应该在选择压力的影响下进化。在本研究中，我们研究了反刍动物 IFI16 样（IFI16-L）PYHIN 基因不同结构域类型的选择压力性质。
在反刍动物（水牛、瘤牛、山羊和绵羊）的 PBMCs 中发现了三个 IFI16 样基因的转录变体。IFI16 样基因具有一个 N 端 PYD 结构域和一个 C 端 HIN-200 结构域，由结构域间连接区隔开。HIN 结构域和结构域间区受到正选择的影响，而 PYD 结构域受到纯化选择的影响。
在此，我们得出结论，选择压力的性质在反刍动物的 IFI16 样 PYHIN 基因的不同部分（PYD 结构域、HIN 结构域和结构域间连接区）上有所不同。这些数据可以帮助预测病原体相互作用的分子决定因素。
