软体动物维甲酸X受体研究进展

维甲酸X受体(retinoid X receptor,RXR)作为配体依赖的转录因子,是核受体超家族重要的一员.脊椎动物RXR与配体及其辅调节因子相互作用,调控基因的协调表达,在胚胎发育、细胞分化、新陈代谢等许多生理过程中起着重要作用.软体动物RXR的研究因其与腹足类性畸变的关系越来越受到关注.本文综述了目前获得的软体动物RXR基因的结构,比较了软体动物RXR基因各功能结构域与人类和其他动物RXR的相似性.以RXR编码区的氨基酸序列为基础,构建了系统进化树,发现软体动物RXR与脊索动物而不是其他无脊椎动物的RXR聚成一支.软体动物和甲壳动物不同RXR亚型的氨基酸序列比较发现,两类动物可能存在不同的剪切酶或剪切位点.此外论文还针对软体动物RXR的配体、二聚体伙伴以及生理功能等方面的研究进行了综述.     

Phylogenetic dating and characterization of gene duplications in vertebrates: the cartilaginous fish reference

Vertebrates originated in the lower Cambrian. Their diversification and morphological innovations have been attributed to large-scale gene or genome duplications at the origin of the group. These duplications are predicted to have occurred in two rounds, the "2R" hypothesis, or they may have occurred in one genome duplication plus many segmental duplications, although these hypotheses are disputed. Under such models, most genes that are duplicated in all vertebrates should have originated during the same period. Previous work has shown that indeed duplications started after the speciation between vertebrates and the closest invertebrate, amphioxus, but have not set a clear ending. Consideration of chordate phylogeny immediately shows the key position of cartilaginous vertebrates (Chondrichthyes) to answer this question. Did gene duplications occur as frequently during the 45 Myr between the cartilaginous/bony vertebrate split and the fish/tetrapode split as in the previous approximately 100 Myr? Although the time interval is relatively short, it is crucial to understanding the events at the origin of vertebrates. By a systematic appraisal of gene phylogenies, we show that significantly more duplications occurred before than after the cartilaginous/bony vertebrate split. Our results support rounds of gene or genome duplications during a limited period of early vertebrate evolution and allow a better characterization of these events.     

Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor

Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as ubiquitous heterodimerization partners of many nuclear receptors. While it has long been accepted that a wide range of ligands can activate vertebrate/mollusc RXRs, the existence and necessity of specific endogenous ligands activating RXR-USP in vivo is still matter of intense debate. Here we report the existence of a novel type of RXR-USP with a ligand-independent functional conformation. Our studies involved Tribolium USP (TcUSP) as representative of most arthropod RXR-USPs, with high sequence homology to vertebrate/mollusc RXRs. The crystal structure of the ligand-binding domain of TcUSP was solved in the context of the functional heterodimer with the ecdysone receptor (EcR). While EcR exhibits a canonical ligand-bound conformation, USP adopts an original apo structure. Our functional data demonstrate that TcUSP is a constitutively silent partner of EcR, and that none of the RXR ligands can bind and activate TcUSP. These findings together with a phylogenetic analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics.     

Evolution of new characters after whole genome duplications: Insights from amphioxus

Additional copies of genes resulting from two whole genome duplications at the base of the vertebrates have been suggested as enabling the evolution of vertebrate-specific structures such as neural crest, a midbrain/hindbrain organizer and neurogenic placodes. These structures, however, did not evolve entirely de novo, but arose from tissues already present in an ancestral chordate. This review discusses the evolutionary history of co-option of old genes for new roles in vertebrate development as well as the relative contributions of changes in cis-regulation and in protein structure. Particular examples are the FoxD, FGF8/17/18 and Pax2/5/8 genes. Comparisons with invertebrate chordates (amphioxus and tunicates) paint a complex picture with co-option of genes into new structures occurring both after and before the whole genome duplications. In addition, while cis-regulatory changes are likely of primary importance in evolution of vertebrate-specific structures, changes in protein structure including alternative splicing are non-trivial.     

Multiple Chromosomal Rearrangements Structured the Ancestral Vertebrate Hox-Bearing Protochromosomes

While the proposal that large-scale genome expansions occurred early in vertebrate evolution is widely accepted, the exact mechanisms of the expansion—such as a single or multiple rounds of whole genome duplication, bloc chromosome duplications, large-scale individual gene duplications, or some combination of these—is unclear. Gene families with a single invertebrate member but four vertebrate members, such as the Hox clusters, provided early support for Ohno's hypothesis that two rounds of genome duplication (the 2R-model) occurred in the stem lineage of extant vertebrates. However, despite extensive study, the duplication history of the Hox clusters has remained unclear, calling into question its usefulness in resolving the role of large-scale gene or genome duplications in early vertebrates. Here, we present a phylogenetic analysis of the vertebrate Hox clusters and several linked genes (the Hox “paralogon”) and show that different phylogenies are obtained for Dlx and Col genes than for Hox and ErbB genes. We show that these results are robust to errors in phylogenetic inference and suggest that these competing phylogenies can be resolved if two chromosomal crossover events occurred in the ancestral vertebrate. These results resolve conflicting data on the order of Hox gene duplications and the role of genome duplication in vertebrate evolution and suggest that a period of genome reorganization occurred after genome duplications in early vertebrates.     

Adaptive Evolution of the STRA6 Genes in Mammalian

Stimulated by retinoic acid 6 (STRA6) is the receptor for retinol binding protein and is relevant for the transport of retinol to specific sites such as the eye. The adaptive evolution mechanism that vertebrates have occupied nearly every habitat available on earth and adopted various lifestyles associated with different light conditions and visual challenges, as well as their role in development and adaptation is thus far unknown. In this work, we have investigated different aspects of vertebrate STRA6 evolution and used molecular evolutionary analyses to detect evidence of vertebrate adaptation to the lightless habitat. Free-ratio model revealed significant rate shifts immediately after the species divergence. The amino acid sites detected to be under positive selection are within the extracellular loops of STRA6 protein. Branch-site model A test revealed that STRA6 has undergone positive selection in the different phyla of mammalian except for the branch of rodent. The results suggest that interactions between different light environments and host may be driving adaptive change in STRA6 by competition between species. In support of this, we found that altered functional constraints may take place at some amino acid residues after speciation. We suggest that STRA6 has undergone adaptive evolution in different branch of vertebrate relation to habitat environment.     

Mapping of the mouse Rxr loci encoding nuclear retinoid X receptors RXR alpha, RXR beta, and RXR gamma.

Recently, a novel subgroup of nuclear hormone receptors called RXRs implicated for retinoid-mediated gene regulation have been identified. RXRs appear to interact with many other nuclear hormone receptors and modulate their functions. We have mapped genetic loci Rxra, Rxrb, and Rxrg encoding three RXR subtypes, RXR alpha, RXR beta, and RXR gamma, respectively, using interspecific backcross mice. None of the Rxr loci cosegregated with each other or with the retinoic acid receptor loci (Rar) mapped previously. Rxra mapped to Chr 2 near the centromere, Rxrb mapped to the H-2 region of Chr 17, and Rxrg was tightly linked to the Pbx gene on distal Chr 1. These results underscore that RXR genes are dispersed in the genome.     

Evolutionary Dynamics of the Interferon-Induced Transmembrane Gene Family in Vertebrates

Vertebrate interferon-induced transmembrane (IFITM) genes have been demonstrated to have extensive and diverse functions, playing important roles in the evolution of vertebrates. Despite observance of their functionality, the evolutionary dynamics of this gene family are complex and currently unknown. Here, we performed detailed evolutionary analyses to unravel the evolutionary history of the vertebrate IFITM family. A total of 174 IFITM orthologous genes and 112 pseudogenes were identified from 27 vertebrate genome sequences. The vertebrate IFITM family can be divided into immunity-related IFITM (IR-IFITM), IFITM5 and IFITM10 sub-families in phylogeny, implying origins from three different progenitors. In general, vertebrate IFITM genes are located in two loci, one containing the IFITM10 gene, and the other locus containing IFITM5 and various numbers of IR-IFITM genes. Conservation of evolutionary synteny was observed in these IFITM genes. Significant functional divergence was detected among the three IFITM sub-families. No gene duplication or positive selection was found in IFITM5 sub-family, implying the functional conservation of IFITM5 in vertebrate evolution, which is involved in bone formation. No IFITM5 locus was identified in the marmoset genome, suggesting a potential association with the tiny size of this monkey. The IFITM10 sub-family was divided into two groups: aquatic and terrestrial types. Functional divergence was detected between the two groups, and five IFITM10-like genes from frog were dispersed into the two groups. Both gene duplication and positive selection were observed in aquatic vertebrate IFITM10-like genes, indicating that IFITM10 might be associated with the adaptation to aquatic environments. A large number of lineage- and species-specific gene duplications were observed in IR-IFITM sub-family and positive selection was detected in IR-IFITM of primates and rodents. Because primates have experienced a long history of viral infection, such rapid expansion and positive selection suggests that the evolution of primate IR-IFITM genes is associated with broad-spectrum antiviral activity.     

Gene duplications and the early evolution of neural crest development

Neural crest cells are an important cell type present in all vertebrates, and elaboration of the neural crest is thought to have been a key factor in their evolutionary success. Genomic comparisons suggest there were two major genome duplications in early vertebrate evolution, raising the possibility that evolution of neural crest was facilitated by gene duplications. Here, we review the process of early neural crest formation and its underlying gene regulatory network (GRN) as well as the evolution of important neural crest derivatives. In this context, we assess the likelihood that gene and genome duplications capacitated neural crest evolution, particularly in light of novel data arising from invertebrate chordates.     

Chromosome number evolves independently of genome size in a clade with nonlocalized centromeres (carex: cyperaceae)

The effects of chromosome rearrangement on genome size are poorly understood. While chromosome duplications and deletions have predictable effects on genome size, chromosome fusion, fission, and translocation do not. In this study, we investigate genome size and chromosome number evolution in 87 species of Carex, one of the most species-rich genera of flowering plants and one that has undergone an exceptionally high rate of chromosome rearrangement. Using phylogenetic generalized least-squares regression, we find that the correlation between chromosome number and genome size in the genus grades from flat or weakly positive at fine phylogenetic scales to weakly negative at deeper phylogenetic scales. The rate of chromosome evolution exhibits a significant increase within a species-rich clade that arose approximately 5 million years ago. Genome size evolution, however, demonstrates a nearly constant rate across the entire tree. We hypothesize that this decoupling of genome size from chromosome number helps explain the high lability of chromosome number in the genus, as it reduces indirect selection on chromosome number.     

Impact of gene gains,losses and duplication modes on the origin and diversification of vertebrates

The study of the evolutionary origin of vertebrates has been linked to the study of genome duplications since Susumo Ohno suggested that the successful diversification of vertebrate innovations was facilitated by two rounds of whole-genome duplication (2R-WGD) in the stem vertebrate. Since then, studies on the functional evolution of many genes duplicated in the vertebrate lineage have provided the grounds to support experimentally this link. This article reviews cases of gene duplications derived either from the 2R-WGD or from local gene duplication events in vertebrates, analyzing their impact on the evolution of developmental innovations. We analyze how gene regulatory networks can be rewired by the activity of transposable elements after genome duplications, discuss how different mechanisms of duplication might affect the fate of duplicated genes, and how the loss of gene duplicates might influence the fate of surviving paralogs. We also discuss the evolutionary relationships between gene duplication and alternative splicing, in particular in the vertebrate lineage. Finally, we discuss the role that the 2R-WGD might have played in the evolution of vertebrate developmental gene networks, paying special attention to those related to vertebrate key features such as neural crest cells, placodes, and the complex tripartite brain. In this context, we argue that current evidences points that the 2R-WGD may not be linked to the origin of vertebrate innovations, but to their subsequent diversification in a broad variety of complex structures and functions that facilitated the successful transition from peaceful filter-feeding non-vertebrate ancestors to voracious vertebrate predators.     

The amphioxus genome enlightens the evolution of the thyroid hormone signaling pathway

Thyroid hormones (THs) have pleiotropic effects on vertebrate development, with amphibian metamorphosis as the most spectacular example. However, developmental functions of THs in non-vertebrate chordates are largely hypothetical and even TH endogenous production has been poorly investigated. In order to get better insight into the evolution of the thyroid hormone signaling pathway in chordates, we have taken advantage of the recent release of the amphioxus genome. We found amphioxus homologous sequences to most of the genes encoding proteins involved in thyroid hormone signaling in vertebrates, except the fast-evolving thyroglobulin: sodium iodide symporter, thyroid peroxidase, deiodinases, thyroid hormone receptor, TBG, and CTHBP. As only some genes encoding proteins involved in TH synthesis regulation were retrieved (TRH, TSH receptor, and CRH receptor but not their corresponding receptors and ligands), there may be another mode of upstream regulation of TH synthesis in amphioxus. In accord with the notion that two whole genome duplications took place at the base of the vertebrate tree, one amphioxus gene often corresponded to several vertebrate homologs. However, some amphioxus specific duplications occurred, suggesting that several steps of the TH pathway were independently elaborated in the cephalochordate and vertebrate lineages. The present results therefore indicate that amphioxus is capable of producing THs. As several genes of the TH signaling pathway were also found in the sea urchin genome, we propose that the thyroid hormone signaling pathway is of ancestral origin in chordates, if not in deuterostomes, with specific elaborations in each lineage, including amphioxus.     

Analysis of lamprey and hagfish genes reveals a complex history of gene duplications during early vertebrate evolution

It has been proposed that two events of duplication of the entire genome occurred early in vertebrate history (2R hypothesis). Several phylogenetic studies with a few gene families (mostly Hox genes and proteins from the MHC) have tried to confirm these polyploidization events. However, data from a single locus cannot explain the evolutionary history of a complete genome. To study this 2R hypothesis, we have taken advantage of the phylogenetic position of the lamprey to study the history of gene duplications in vertebrates. We selected most gene families that contain several paralogous genes in vertebrates and for which lamprey genes and an out-group are known in databases. In addition, we isolated members of the nuclear receptor superfamily in lamprey. Hagfish genes were also analyzed and found to confirm the lamprey gene analysis. Consistent with the 2R hypothesis, the phylogenetic analysis of 33 selected gene families, dispersed through the whole genome, revealed that one period of gene duplication arose before the lamprey-gnathostome split and this was followed by a second period of gene duplication after the lamprey-gnathostome split. Nevertheless, our analysis suggests that numerous gene losses and other gene-genome duplications occurred during the evolution of the vertebrate genomes. Thus, the complexity of all the paralogy groups present in vertebrates should be explained by the contribution of genome duplications (2R hypothesis), extra gene duplications, and gene losses.     

Selection on coding regions determined Hox7 genes evolution

The important role of Hox genes in determining the regionalization of the body plan of the vertebrates makes them invaluable candidates for evolutionary analyses regarding functional and morphological innovation. Gene duplication and gene loss led to a variable number of Hox genes in different vertebrate lineages. The evolutionary forces determining the conservation or loss of Hox genes are poorly understood. In this study, we show that variable selective pressures acted on Hox7 genes in different evolutionary lineages, with episodes of positive selection occurring after gene duplications. Tests for functional divergence in paralogs detected significant differentiation in a region known to modulate HOX7 protein activity. Our results show that both positive and negative selection on coding regions are influencing Hox7 genes evolution.     

Evolutionary Conservation in Retinoid Signalling and Metabolism

In accord with the notion that retinoid signalling is of centralimportance in vertebrate evolution, a number of its componentsare evolutionarily conserved. Retinoid X nuclear receptors (RXRs),which interact directly with a number of signalling pathways,are highly conserved among mammals, Xenopus, and chick. We havestudied RXRs in zebrafish and find that they are also very wellconserved with respect to amino acid sequence and function,compared to mammalian RXRs. However, zebrafish has additionalsubtypes (RXR and RXR) which are altered in structure and function.New information which has come to light since these were firstdescribed suggests ways in which these unique subtypes couldfine-tune retinoid signalling in zebrafish. We have performedphylogenetic analysis with the zebrafish RXRs and RXRs fromother species to try to understand the evolutionary relationshipsamong them. In addition, we have found a retinoic acid (RA)-inducible,RA-metabolizing cytochrome P450 (P450RAI/CYP26) which is evolutionarilyconserved among vertebrates and has an important role in controllingretinoid signalling by regulating the level of biologicallyavailable RA.     

A genetic model for the evolution of the glycosphingolipids

The glycosphingolipids have been found in many animal tissues, but the complexity of their molecular structure varies considerably among the different phyla. Relatively simple structures have been found in invertebrate species, while the most complex have been demonstrated in brain tissue of modern fishes and amphibians. The data on the phylogenetic distribution of the glycosphingolipids has been interpreted to indicate that a significant number of gene duplications, involving many different structural genes, may have occurred during a few specific periods of vertebrate evolution. The transition from invertebrate to jawless vertebrate, the divergence of rays and skates from true sharks, the advent of modern bony fishes and the transition from aquatic to terrestrial vertebrates, each could have veen accompained by duplications of genes involved in the synthesis and degradation of glycosphingolipids. The evolutionary study of such a multi-enzyme system may be one means to detect alterations in the genome as a whole. The apparent correspondence in time of these gene duplications involved in glycosphingolipid metabolism and periods of rapid vertebrate evolution which may have been accompanied by significant increases in the amount of cellular DNA suggests that such changes may have occurred via the mechanism of tetraploidization.     

RXR-2, a member of the retinoid x receptor family in Schistosoma mansoni.

A cDNA encoding a second full-length member of the Schistosoma mansoni RXR family (SmRXR-2) was identified. The nucleotide sequence of SmRXR-2 translates into a protein of 784 amino acids with a pI of 7.63 and an approximate mass of 78kDa making it the largest reported RXR to date. Phylogenetic tree analysis provides evidence that SmRXR-2 is the most ancient full-length RXR identified. SmRXR-2 exhibits unique sequence features compared with other RXRs. RT-PCR results demonstrate that the SmRXR-2 gene is constitutively expressed and thus must play multiple roles throughout schistosome development in the vertebrate host.