Evolution of Klk4 and enamel maturation in eutherians.

Evolution of Klk4 and enamel maturation in eutherians.
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DOI:
10.1515/hsz-2014-0122
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发表时间:
2014-09
影响因子:
3.7
通讯作者:
Simmer JP
Simmer JP
中科院分区:
生物学2区
文献类型:
--
作者:
Kawasaki K;Hu JC;Simmer JP

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激肽释放酶相关多肽酶4(KLK4)是一种分泌型丝氨酸蛋白酶,能降解残留的釉质蛋白,促进成釉细胞将其去除,从而增加矿化并使釉质变硬。人类KLK4基因突变导致成釉发育不全。Klk4基因缺失小鼠形成的釉质厚度和棱柱结构正常,但釉质层保留蛋白质,矿化程度低,在牙齿萌出后经历快速磨损。我们搜索了多个数据库,从各种哺乳动物基因组中检索到Klk4和Klk5,并在47个北真核基因组中鉴定出Klk4。在非Boreoeutheria中,仅在一个非有袋类基因组中检测到Klk4(作为假基因),而在其他六个非有袋类、两个Xenarthran或三个有袋类基因组中未检测到Klk4。相比之下,Klk5在有袋类和真兽类哺乳动物中都被检测到。我们的系统发育和突变率分析支持这一假说,即Klk4是通过在Afotheria、Xenarthra和Boreoeutheria分歧附近的基因复制而产生的,而功能分化的Klk4只在Boreoeutheria中存活。与非真兽类哺乳动物相比,非泡沫类哺乳动物具有牙齿萌出延迟的特征。KLK4缩短了牙釉质成熟所需的时间,并可能缓解了导致牙釉质更厚或更早萌出的突变后的负面选择,而不会降低牙釉质硬度或导致牙齿磨损。
Kallikrein-related peptidase 4 (KLK4) is a secreted serine protease that degrades residual enamel proteins to facilitate their removal by ameloblasts, which increases mineralization and hardens the enamel. Mutations in human KLK4 cause hypomaturation amelogenesis imperfecta. Enamel formed by Klk4 null mice is normal in thickness and prism structure, but the enamel layer retains proteins, is hypomineralized, and undergoes rapid attrition following tooth eruption. We searched multiple databases, retrieved Klk4 and Klk5 from various mammalian genomes, and identified Klk4 in 47 boreoeutherian genomes. In non-Boreoeutheria, Klk4 was detected in only one afrotherian genome (as a pseudogene), and not in the other six afrotherian, two xenarthran, or three marsupial genomes. In contrast, Klk5 was detected in both marsupial and eutherian mammals. Our phylogenetic and mutation rate analyses support the hypothesis that Klk4 arose from Klk5 by gene duplication near the divergence of Afrotheria, Xenarthra and Boreoeutheria, and that functionally- differentiated Klk4 survived only in Boreoeutheria. Afrotherian mammals share the feature of delayed dental eruption relative to boreoeutherian mammals. KLK4 shortens the time required for enamel maturation and could have alleviated negative selection following mutations that resulted in thicker enamel or earlier tooth eruption, without reducing enamel hardness or causing dental attrition.
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