MEPE evolution in mammals reveals regions and residues of prime functional importance

MEPE evolution in mammals reveals regions and residues of prime functional importance
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DOI:
10.1007/s00018-009-0185-1
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发表时间:
2010-01-01
影响因子:
8
通讯作者:
Sire, Jean-Yves
Sire, Jean-Yves
中科院分区:
生物学1区
文献类型:
--
作者:
Bardet, Claire;Delgado, Sidney;Sire, Jean-Yves

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在哺乳动物中,基质细胞外磷酸糖蛋白 (MEPE) 已知可通过称为牙本质的特定区域激活成骨和矿化,并通过其 ASARM(富含酸性丝氨酸-天冬氨酸的 MEPE 相关基序)肽抑制矿化,该肽也在磷血症调节中发挥作用。为了了解哺乳动物MEPE的进化,特别是其功能区的进化,我们基于选择压力的研究进行了进化分析。使用 37 个哺乳动物序列,我们:(1) 证实大多数胎盘中存在额外的编码外显子; (2) 强调了几个可能具有重要功能的保守残基和区域; (3) 发现牙本质功能在胎盘祖先中被招募; (4) 揭示了 ASARM 功能较早出现,将 MEPE 的招募推向羊膜起源深处。我们的数据表明,MEPE 在获得目前已知的胎盘哺乳动物功能之前就参与了各种功能(骨和蛋壳矿化)。
In mammals, the matrix extracellular phosphoglycoprotein (MEPE) is known to activate osteogenesis and mineralization via a particular region called dentonin, and to inhibit mineralization via its ASARM (acidic serine-aspartate rich MEPE-associated motif) peptide that also plays a role in phosphatemia regulation. In order to understand MEPE evolution in mammals, and particularly that of its functional regions, we conducted an evolutionary analysis based on the study of selective pressures. Using 37 mammalian sequences we: (1) confirmed the presence of an additional coding exon in most placentals; (2) highlighted several conserved residues and regions that could have important functions; (3) found that dentonin function was recruited in a placental ancestor; and (4) revealed that ASARM function was present earlier, pushing the recruitment of MEPE deep into amniote origins. Our data indicate that MEPE was involved in various functions (bone and eggshell mineralization) prior to acquiring those currently known in placental mammals.