Data from: Analysis of hypoxia-inducible factor alpha polyploidization reveals adaptation to Tibetan plateau in the evolution of schizothoracine fish

Background: Hypoxia-inducible factor (HIF) is a master regulator that mediates major changes in gene expression under hypoxic conditions. Though HIF family has been identified in many organisms, little is known about this family in schizothoracine fish. Results: Duplicated hif-α (hif-1αA, hif-1αB, hif-2αA, and hif-2αB) genes were identified in schizothoracine fish. All the deduced HIF-α proteins contain the main domains (bHLH-PAS, ODDD, and TAD), also found in humans. Evidence suggests a Cyprinidae-specific deletion, specifically, a conserved proline hydroxylation motif LxxLAP, in the NODD domain of schizothoracine fish HIF-1αA. In addition, a schizothoracine-specific mutation was observed in the CODD domain of the specialized and highly specialized schizothoracine fish HIF-1αB, which is the proline hydroxylation motif mutated into PxxLAP. Standard and stochastic branch-site codon model analysis indicated that only HIF-1αB has undergone positive selection, which may have led to changes in function. To confirm this hypothesis, HIF-αs tagged with Myc were transfected into HEK 293 T cells. Each HIF-1αB was found to significantly upregulate luciferase activity under normoxic and hypoxic conditions, which indicated that the HIF-1αB protein was more stable than other HIF-αs. Conclusions: All deduced HIF-α proteins of schizothoracine fish contain important domains, like their mammalian counterparts, and each HIF-α is shorter than that of human. Our experiments reveal that teleost-specific duplicated hif-α genes played different roles under hypoxic conditions, and HIF-1αB may be the most important regulator in the adaptation of schizothoracine fish to the environment of the Tibetan Plateau.背景：缺氧诱导因子（Hypoxia-inducible factor, HIF）是介导低氧条件下基因表达发生重大变化的核心调控因子。尽管已在众多生物中鉴定出HIF家族成员，但目前对裂腹鱼（schizothoracine fish）中的该家族基因所知甚少。结果：本研究在裂腹鱼中鉴定出复制型hif-α基因（hif-1αA、hif-1αB、hif-2αA及hif-2αB）。所有推导得到的HIF-α蛋白均包含与人类同源蛋白一致的核心结构域（bHLH-PAS、ODDD及TAD）。研究发现，裂腹鱼HIF-1αA的N端氧依赖降解结构域（NODD）存在鲤科（Cyprinidae）特异性缺失，具体为保守的脯氨酸羟化基序LxxLAP发生缺失。此外，特化及高度特化的裂腹鱼HIF-1αB的C端氧依赖降解结构域（CODD）存在裂腹鱼特异性突变，即将脯氨酸羟化基序突变为PxxLAP。通过标准分支位点密码子模型及随机分支位点密码子模型分析显示，仅HIF-1αB发生了正选择，这可能导致其功能发生改变。为验证该假说，本研究将带有Myc标签的HIF-α基因转染至HEK 293 T细胞中，结果显示，在常氧及低氧条件下，所有HIF-1αB均能显著上调荧光素酶活性，表明HIF-1αB蛋白较其他HIF-α蛋白更为稳定。结论：裂腹鱼所有推导得到的HIF-α蛋白均包含与哺乳动物同源蛋白一致的重要结构域，且各HIF-α蛋白的长度均短于人类同源蛋白。本研究实验结果表明，硬骨鱼特异性复制的hif-α基因在低氧条件下发挥着不同的功能，而HIF-1αB可能是裂腹鱼适应青藏高原（Tibetan Plateau）环境的核心调控因子。