Genome-Wide Characterization of the Nuclear Receptor Gene Family in Macrostomum lignano Imply Its Evolutionary Diversification

Abstract

Nuclear receptors (NRs), a series of key transcription factors that are mostly activated by endogenous ligands or environmental xenobiotics, are reportedly good phylogenetic markers of animal genome evolution. As the early diverging class of bilaterians, however, a comprehensive view of the NR family in a marine free-living flatworm Macrostomum lignano and comparative information in flatworms are still lacking, which is of significance to address the evolutionary diversification of the NR family and imply the adaptive evolution in the early diverging Bilateria. Herein, a total of 51, 26, and 23 putative NR genes were identified in M. lignano, Sparganum proliferum, and Clonorchis sinensis, respectively, which were classified into eight subfamilies, implying an extensive expansion of the NR family in M. lignano. It is presumed that the extensive expansion was mainly attributed to the M. lignano-specific hidden polyploidy, segmental, and tandem duplication events. The duplicated NR pairs in M. lignano and the NR orthologs in flatworms all experienced the purifying selection. Phylogenetic analyses indicated the presence of NR3-like genes in M. lignano, which is first reported in flatworms. Intron loss and reduced intron size were mainly contributed to the structural divergence of NR genes in flatworms. The combined data provide indispensable information for a better understanding of the complexity and the adaptive evolution of the NR gene family in metazoans.

Updated knowledge and a proposed nomenclature for nuclear receptors with two DNA binding domains (2DBD-NRs)

“…Our previous study showed that two 2DBD-NRs were present in Rhabditophora Macrostomum lignano [ 16 , 21 ] and four in Schmidtea mediterranea . Three members were present in parasitic species from Platyhelminths including Class Monogenea, Cestoda and Trematoda, respectively [ 12 , 14 , 15 , 17 – 21 ].…”

Updated knowledge and a proposed nomenclature for nuclear receptors with two DNA Binding Domains (2DBD-NRs)

“…Previously, we suggested placing 2DBD-NRs in a new NR subfamily (NR subfamily 7, NR7) when we discovered the 2DBD-NRs [6,8] and this was accepted by some other studies [10,44,45]. However, NR7 was recently used to describe NRs [46] previously known as NR8 members [45] and amphioxus NR1Hs [27,47].…”

“…Phylogenetic analysis of DBD sequences showed that all of these 2DBD-NRs belonged to a monophyletic group and suggested that 2DBD-NRs originated from a common ancestor gene [8]. Recently, 2DBD-NRs were only identified and/or isolated in Platyhelminths [6,[8][9][10][11][12][13][14][15] and in Mollusca [16,17]. Until now, there are very few studies on 2DBD-NRs.…”

Perspective Chapter: Parasitic Platyhelminthes Nuclear Receptors as Molecular Crossroads

“…For a long time, it has not been possible to identify subfamily 3 NRs in Platyhelminthes [21,72], so this class of proteins seems to have been lost in this phylum. However, recent genome sequence analysis studies identified several ERRs (estrogen-related receptor) belonging to subfamily 3 [37,49].…”

“…This new group has not yet been included in the classification system described by the NR Nomenclature Committee [21,34]. However, recent publications already classify it as a subfamily NR7 [37]. Furthermore, nuclear receptors can be classified according to their mechanism of action into four types (I-IV).…”