Laudet V
URA1160 du CNRS Oncologie Moléculaire, Institut de Biologie de Lille, Institut Pasteur de Lille, France.
J Mol Endocrinol. 1997 Dec;19(3):207-26. doi: 10.1677/jme.0.0190207.
From a database containing the published nuclear hormone receptor (NR) sequences I constructed an alignment of the C, D and E domains of these molecules. Using this alignment, I have performed tree reconstruction using both distance matrix and parsimony analysis. The robustness of each branch was estimated using bootstrap resampling methods. The trees constructed by these two methods gave congruent topologies. From these analyses I defined six NR subfamilies: (i) a large one clustering thyroid hormone receptors (TRs), retinoic acid receptors (RARs), peroxisome proliferator-activated receptors (PPARs), vitamin D receptors (VDRs) and ecdysone receptors (EcRs) as well as numerous orphan receptors such as RORs or Rev-erbs; (ii) one containing retinoid X receptors (RXRs) together with COUP, HNF4, tailless, TR2 and TR4 orphan receptors; (iii) one containing steroid receptors; (iv) one containing the NGFIB orphan receptors; (v) one containing FTZ-F1 orphan receptors; and finally (vi) one containing to date only one gene, the GCNF1 orphan receptor. The relationships between the six subfamilies are not known except for subfamilies I and IV which appear to be related. Interestingly, most of the liganded receptors appear to be derived when compared with orphan receptors. This suggests that the ligand-binding ability of NRs has been gained by orphan receptors during the course of evolution to give rise to the presently known receptors. The distribution into six subfamilies correlates with the known abilities of the various NRs to bind to DNA as homo- or heterodimers. For example, receptors heterodimerizing efficiently with RXR belong to the first or the fourth subfamilies. I suggest that the ability to heterodimerize evolved once, just before the separation of subfamilies I and IV and that the first NR was able to bind to DNA as a homodimer. From the study of NR sequences existing in vertebrates, arthropods and nematodes, I define two major steps of NR diversification: one that took place very early, probably during the multicellularization event leading to all the metazoan phyla, and a second occurring later on, corresponding to the advent of vertebrates. Finally, I show that in vertebrate species the various groups of NRs accumulated mutations at very different rates.
我从一个包含已发表的核激素受体（NR）序列的数据库中构建了这些分子C、D和E结构域的比对。利用这个比对结果，我通过距离矩阵和简约分析进行了系统树重建。使用自展重抽样方法估计每个分支的稳健性。这两种方法构建的系统树给出了一致的拓扑结构。通过这些分析，我定义了六个NR亚家族：（i）一个大的亚家族，聚集了甲状腺激素受体（TRs）、视黄酸受体（RARs）、过氧化物酶体增殖物激活受体（PPARs）、维生素D受体（VDRs）和蜕皮激素受体（EcRs）以及许多孤儿受体，如RORs或Rev-erbs；（ii）一个包含视黄酸X受体（RXRs）以及COUP、HNF4、无尾、TR2和TR4孤儿受体；（iii）一个包含类固醇受体；（iv）一个包含NGFIB孤儿受体；（v）一个包含FTZ-F1孤儿受体；最后（vi）一个目前仅包含一个基因，即GCNF1孤儿受体。除了似乎相关的亚家族I和IV之外，六个亚家族之间的关系尚不清楚。有趣的是，与孤儿受体相比，大多数有配体结合的受体似乎是衍生而来的。这表明在进化过程中，孤儿受体获得了NR的配体结合能力，从而产生了目前已知的受体。分为六个亚家族的情况与各种NR作为同二聚体或异二聚体结合DNA的已知能力相关。例如，能与RXR高效异二聚化的受体属于第一或第四亚家族。我认为异二聚化能力在亚家族I和IV分离之前仅进化了一次，并且第一个NR能够作为同二聚体结合DNA。通过对脊椎动物、节肢动物和线虫中存在的NR序列的研究，我定义了NR多样化的两个主要阶段：一个非常早发生，可能在导致所有后生动物门的多细胞化事件期间，另一个稍后发生，与脊椎动物的出现相对应。最后，我表明在脊椎动物物种中，不同组的NR以非常不同的速率积累突变。
