我们确定了五个不同的全长人盐皮质激素受体(MR)基因,包含984个氨基酸(MR-984)或988个氨基酸(MR-988)。可以通过Lys的存在或不存在来区分,Cys,Ser,和Trp(KCSW)在它们的DNA结合结构域(DBD)中以及在它们的氨基末端结构域(NTD)中的密码子180和241处的突变。两个人MR-KCSW基因在其NTD中包含(Val-180,Val-241)或(Ile-180,Val-241),和三个人类MR-984基因包含(Ile-180,Ala-241),(Val-180,Val-241),或(Ile-180,Val-241)。尚未克隆具有(Ile-180,Ala-241)的人MR-KCSW。相比之下,黑猩猩包含四个MR:两个MR-988,其DBD中有KCSW,或两台DBD中没有KCSW的MR-984。黑猩猩MR在其NTD中仅包含(Ile180,Val-241)。尚未克隆在NTD中具有(Val-180,Val-241)或(Ile-180,Ala-241)的黑猩猩MR。大猩猩和猩猩各自包含一个在DBD中带有KCSW的MR-988和一个没有KCSW的MR-984,并且这些MR在其NTD中仅包含(Ile-180,Val-241)。尚未克隆NTD中具有(Val-180,Val-241)或(Ile-180,Ala-241)的大猩猩MR或猩猩MR。一起,这些数据表明,在NTD中具有(Val-180,Val-241)或(Ile-180,Ala-241)的人类MR是在人类和黑猩猩从其共同祖先分化后进化而来的。考虑到肾脏MR在人类发育中的多种功能,大脑,心,皮肤,和肺,以及与糖皮质激素受体相互作用的MR活性,我们认为,黑猩猩中不存在的人类MR的进化可能对人类从黑猩猩的进化很重要。人体MR介导的皮质类固醇生理反应的研究,黑猩猩,大猩猩,猩猩和猩猩可以提供对人类及其近亲进化的见解。
We identified five distinct full-length human mineralocorticoid receptor (MR) genes containing either 984 amino acids (MR-984) or 988 amino acids (MR-988), which can be distinguished by the presence or absence of Lys, Cys, Ser, and Trp (KCSW) in their DNA-binding domain (DBD) and mutations at codons 180 and 241 in their amino-terminal domain (NTD). Two human MR-KCSW genes contain either (Val-180, Val-241) or (Ile-180, Val-241) in their NTD, and three human MR-984 genes contain either (Ile-180, Ala-241), (Val-180, Val-241), or (Ile-180, Val-241). Human MR-KCSW with (Ile-180, Ala-241) has not been cloned. In contrast, chimpanzees contain four MRs: two MR-988s with KCSW in their DBD, or two MR-984s without KCSW in their DBD. Chimpanzee MRs only contain (Ile180, Val-241) in their NTD. A chimpanzee MR with either (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD has not been cloned. Gorillas and orangutans each contain one MR-988 with KCSW in the DBD and one MR-984 without KCSW, and these MRs only contain (Ile-180, Val-241) in their NTD. A gorilla MR or orangutan MR with either (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD has not been cloned. Together, these data suggest that human MRs with (Val-180, Val-241) or (Ile-180, Ala-241) in the NTD evolved after humans and chimpanzees diverged from their common ancestor. Considering the multiple functions in human development of the MR in kidney, brain, heart, skin, and lungs, as well as MR activity in interaction with the glucocorticoid receptor, we suggest that the evolution of human MRs that are absent in chimpanzees may have been important in the evolution of humans from chimpanzees. Investigation of the physiological responses to corticosteroids mediated by the MR in humans, chimpanzees, gorillas, and orangutans may provide insights into the evolution of humans and their closest relatives.