Proteomic comparison of human and great ape blood plasma reveals conserved glycosylation and differences in thyroid hormone metabolism
Proteomic comparison of human and great ape blood plasma reveals conserved glycosylation and differences in thyroid hormone metabolism
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DOI：
10.1002/ajpa.1061
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发表时间：
2001-06-01
影响因子：
2.8
通讯作者：
Varki, A
中科院分区：
文献类型：
--
作者：
Gagneux, P;Amess, B;Varki, A
大多数血浆蛋白是糖基化的。这些糖蛋白通常携带带有唾液酸的糖链，可以改变电泳分析过程中观察到的这些蛋白质的分子量和等电点。为了探索类人猿和人类进化过程中蛋白质表达和糖基化的变化，我们对所有这些物种的多个血浆样本进行了高分辨率蛋白质组分析。我们发现很少有物种特异性差异，这表明血浆蛋白表达和糖基化在大约 1200 万年的进化过程中具有显着的保守性。在类人猿中，蛋白质迁移存在一些谱系特异性差异。人类和所有类人猿之间唯一明显的差异是运甲状腺素蛋白（前白蛋白）明显减少和触珠蛋白亚型发生变化（后者可以从先前的遗传学研究中预测）。对血浆（主要由肝脏合成）和脑脊液（由大脑脉络丛局部合成）样本中转甲状腺素蛋白的定量研究证实，黑猩猩中的转甲状腺素蛋白水平比人类高出两倍。由于转甲状腺素蛋白与甲状腺激素结合，我们接下来比较了人类和黑猩猩之间的血浆甲状腺激素参数。结果表明甲状腺激素代谢状态存在显着差异，这代表了这些物种之间第一个已知的内分泌差异。值得注意的是，甲状腺激素在许多器官和组织（包括大脑和颅骨）的发育、分化和代谢中发挥着重要作用。此外，甲状腺素运载蛋白是脑脊液中甲状腺激素的主要载体，可能调节这种激素向大脑的输送。还注意到类维生素A（维生素A）代谢的潜在次要差异。讨论了这些发现对于解释人类进化的独特特征的意义。 (C) 2001 Wiley-Liss, Inc.
Most blood plasma proteins are glycosylated. These glycoproteins typically carry sialic acid-bearing sugar chains, which can modify the observed molecular weights and isoelectric points of those proteins during electrophoretic analyses. To explore changes in protein expression and glycosylation that occurred during great ape and human evolution, we subjected multiple blood plasma samples from all these species to high-resolution proteomic analysis. We found very few species-specific differences, indicating a remarkable degree of conservation of plasma protein expression and glycosylation during similar to 12 million years of evolution. A few lineage-specific differences in protein migration were noted among the great apes. The only obvious differences between humans and all great apes were an apparent decrease in transthyretin (prealbumin) and a change in haptoglobin isoforms (the latter was predictable from prior genetic studies). Quantitative studies of transthyretin in samples of blood plasma (synthesized primarily by the liver) and of cerebrospinal fluid (synthesized locally by the choroid plexus of the brain) confirmed similar to2-fold higher levels in chimpanzees compared to humans. Since transthyretin binds thyroid hormones, we next compared plasma thyroid hormone parameters between humans and chimpanzees. The results indicate significant differences in the status of thyroid hormone metabolism, which represent the first known endocrine difference between these species. Notably, thyroid hormones are known to play major roles in the development, differentiation, and metabolism of many organs and tissues, including the brain and the cranium. Also, transthyretin is known to be the major carrier of thyroid hormone in the cerebrospinal fluid, likely regulating delivery of this hormone to the brain. A potential secondary difference in retinoid (vitamin A) metabolism is also noted. The implications of these findings for explaining unique features of human evolution are discussed. (C) 2001 Wiley-Liss, Inc.