Chakrabarty Anindita, MacLean James A, Hughes Austin L, Roberts R Michael, Green Jonathan A
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
J Mol Evol. 2006 Aug;63(2):274-82. doi: 10.1007/s00239-005-0264-3. Epub 2006 Jul 7.
The trophoblast Kunitz domain proteins (TKDPs) are products of the outer cells (trophoblasts) of the placenta of cattle, sheep, and related species. Most are expressed abundantly for only a few days during the time at which the ruminant conceptus is first establishing intimate contacts with the uterine lining. The TKDPs are secretory proteins that possess a carboxyl-terminal peptidase inhibitory domain related to the Kunitz family of serine peptidase inhibitors. On the amino-terminal end are one or more highly unusual regions that are unique to the TKDP genes and have no apparent similarity to any other known sequences. The TKDPs are a rather divergent family that exhibits a good deal of variation among the members. To better understand the reason for such variation, the rates of synonymous (dS) and nonsynonymous (dN), as well as radical (pNR) and conservative (pNC), substitutions were assessed. Phylogenetic trees revealed that the Kunitz domains represented three related groups, whereas the amino-terminal domains formed four groupings. Pairwise comparisons between Kunitz and amino-terminal domain groups demonstrated that dN was consistently greater than dS. In addition, nonsynonymous substitutions in the Kunitz domains tended to be radical (changing charge or polarity), while those in the amino-terminal domains exhibited neither a preponderance of conservative nor radical substitution rates. In summary, the rapid evolution of the TKDPs, coupled with their restricted temporal expression during development, likely reflects the establishment of protein-protein interactions that have evolved to serve the unusual synepitheliochorial placenta of ruminant ungulates.
滋养层Kunitz结构域蛋白（TKDPs）是牛、羊及相关物种胎盘外层细胞（滋养层细胞）的产物。大多数TKDPs仅在反刍动物胚胎与子宫内膜首次建立紧密联系的几天内大量表达。TKDPs是分泌蛋白，其羧基末端具有与丝氨酸肽酶抑制剂Kunitz家族相关的肽酶抑制结构域。在氨基末端有一个或多个高度独特的区域，这些区域是TKDP基因所特有的，与任何其他已知序列均无明显相似性。TKDPs是一个差异较大的家族，成员之间存在很大差异。为了更好地理解这种差异的原因，评估了同义替换率（dS）和非同义替换率（dN），以及激进替换率（pNR）和保守替换率（pNC）。系统发育树显示，Kunitz结构域代表三个相关组，而氨基末端结构域形成四个组。Kunitz结构域组和氨基末端结构域组之间的成对比较表明，dN始终大于dS。此外，Kunitz结构域中的非同义替换往往是激进的（改变电荷或极性），而氨基末端结构域中的非同义替换既没有保守替换率优势，也没有激进替换率优势。总之，TKDPs的快速进化，以及它们在发育过程中受限的时间表达，可能反映了蛋白质-蛋白质相互作用的建立，这种相互作用已经进化以适应反刍有蹄类动物不寻常的上皮绒毛膜胎盘。
