Functionally important glycosyltransferase gain and loss during catarrhine primate emergence
Functionally important glycosyltransferase gain and loss during catarrhine primate emergence
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DOI：
10.1073/pnas.0610012104
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发表时间：
2007-01-09
影响因子：
11.1
通讯作者：
Goodman, Morris
中科院分区：
文献类型：
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作者：
Koike, Chihiro;Uddin, Monica;Goodman, Morris
糖基转移酶α-1，3-半乳糖基转移酶催化低聚糖细胞表面表位Galα-1，3Gal-β1-4GlcNAc-R(α-Gal)的生物合成。这种表位或抗原性相似的表位广泛分布在不同的生命形式中。虽然在大多数哺乳动物中大量存在，但卡他灵长类动物(东半球的猴子和类人猿，包括人类)中通常不会发现AGAL，所有这些灵长类动物从婴儿时期就会产生抗α-Gal抗体。自然选择有利于增强对阿尔法-半乳糖阳性病原体的抵抗力，这是卡他那类动物失去AGA的主要原因。在这里，我们质疑这种免疫防御假说的首要地位，结果阐明了GGTA1基因和假基因座位的进化史。其中一个这样的基因座GGTA1P，是一种加工过的(无内含子)假基因(PPG)，存在于鸭嘴兽，即新大陆猴子和卡他猴中，但不存在于原猿类中。PPG起源于类人猿(卡特龙和鸭嘴兽)的早期祖先，GGTA1本身成为卡特龙晚期干谱系中一个未经处理的假基因。在非卡他类哺乳动物中，GGTA1保留了较强的纯化选择，表明该功能基因产物受到相当大的生理限制。因此，我们认为，在GGTA1失活之前，必须首先在主干卡他命中进化出一种替代的和/或更有益的糖基转移酶活性模式。增强对agal阳性病原体的防御能力，可能会加速将agal阳性卡他症替换为阿尔法半乳糖阴性卡他症。然而，我们强调，糖链代谢中积极选择的调节变化很可能在卡他性鼻炎的起源中起到了重要作用。
A glycosyltransferase, alpha 1,3galactosyltransferase, catalyzes the terminal step in biosynthesis of Gal alpha 1,3Gal beta 1-4GlcNAc-R (alpha Gal), an oligosaccharide cell surface epitope. This epitope or antigenically similar epitopes are widely distributed among the different forms of life. Although abundant in most mammals, aGal is not normally found in catarrhine primates (Old World monkeys and apes, including humans), all of which produce anti-alpha Gal antibodies from infancy onward. Natural selection favoring enhanced resistance to alpha Gal-positive pathogens has been the primary reason offered to account for the loss of aGal in catarrhines. Here, we question the primacy of this immune defense hypothesis with results that elucidate the evolutionary history of GGTA1 gene and pseudogene loci. One such locus, GGTA1P, a processed (intronless) pseudogene (PPG), is present in platyrrhines, i.e., New World monkeys, and catarrhines but not in prosimians. PPG arose in an early ancestor of anthropoids (catarrhines and platyrrhines), and GGTA1 itself became an unprocessed pseudogene in the late catarrhine stem lineage. Strong purifying selection, denoted by low nonsynonymous substitutions per nonsynonymous site/synonymous substitutions per synonymous site values, preserved GGTA1 in noncatarrhine mammals, indicating that the functional gene product is subjected to considerable physiological constraint. Thus, we propose that a pattern of alternative and/or more beneficial glycosyltransferase activity had to first evolve in the stem catarrhines before GGTA1 inactivation could occur. Enhanced defense against aGal-positive pathogens could then have accelerated the replacement of aGal-positive catarrhines by alpha Gal-negative catarrhines. However, we emphasize that positively selected regulatory changes in sugar chain metabolism might well have contributed in a major way to catarrhine origins.