From hormones to secondary metabolism: the emergence of metabolic gene clusters in plants

Gene clusters for the synthesis of secondary metabolites are a common feature of microbial genomes. Well-known examples include clusters for the synthesis of antibiotics in actinomycetes, and also for the synthesis of antibiotics and toxins in filamentous fungi. Until recently it was thought that genes for plant metabolic pathways were not clustered, and this is certainly true in many cases; however, five plant secondary metabolic gene clusters have now been discovered, all of them implicated in synthesis of defence compounds. An obvious assumption might be that these eukaryotic gene clusters have arisen by horizontal gene transfer from microbes, but there is compelling evidence to indicate that this is not the case. This raises intriguing questions about how widespread such clusters are, what the significance of clustering is, why genes for some metabolic pathways are clustered and those for others are not, and how these clusters form. In answering these questions we may hope to learn more about mechanisms of genome plasticity and adaptive evolution in plants. It is noteworthy that for the five plant secondary metabolic gene clusters reported so far, the enzymes for the first committed steps all appear to have been recruited directly or indirectly from primary metabolic pathways involved in hormone synthesis. This may or may not turn out to be a common feature of plant secondary metabolic gene clusters as new clusters emerge.     

What Are Imprinted Genes Doing in the Brain?

As evidence for the existence of brain?expressed imprinted genes accumulates, we need to address exactly what they are doing in this tissue, especially in terms of organizational themes and the major challenges posed by reconciling imprinted gene action in brain with current evolutionary theories attempting to explain the origin and maintenance of genomic imprinting. We are at the beginning of this endeavor and much work remains to be done but already it is clear that imprinted genes have the potential to influence diverse behavioral processes via multiple brain mechanisms. There are also grounds to believe that imprinting may contribute to risk of mental and neurological disease. As well as being a source of basic information about imprinted genes in the brain (e.g., via the newly established website, www.bgg.cardiff.ac.uk/imprinted_tables/index.html), we have used this chapter to identify and focus on a number of key questions. How are brain?expressed imprinted genes organized at the molecular and cellular levels? To what extent does imprinted action depend on neurodevelopmental mechanisms? Do imprinted gene effects interact with other epigenetic influences, especially early on in life? Are imprinted effects on adult behaviors adaptive or just epiphenomena? If they are adaptive, what areas of brain function and behavior might be sensitive to imprinted effects? These are big questions and, as shall become apparent, we need much more data, arising from interactions between behavioral neuroscientists, molecular biologists and evolutionary theorists, if we are to begin to answer them.     

The rise and fall of Hox gene clusters

Although all bilaterian animals have a related set of Hox genes, the genomic organization of this gene complement comes in different flavors. In some unrelated species, Hox genes are clustered; in others, they are not. This indicates that the bilaterian ancestor had a clustered Hox gene family and that, subsequently, this genomic organization was either maintained or lost. Remarkably, the tightest organization is found in vertebrates, raising the embarrassingly finalistic possibility that vertebrates have maintained best this ancestral configuration. Alternatively, could they have co-evolved with an increased ;organization' of the Hox clusters, possibly linked to their genomic amplification, which would be at odds with our current perception of evolutionary mechanisms? When discussing the why's and how's of Hox gene clustering, we need to account for three points: the mechanisms of cluster evolution; the underlying biological constraints; and the developmental modes of the animals under consideration. By integrating these parameters, general conclusions emerge that can help solve the aforementioned dilemma.     

Evolution of Conserved Non-Coding Sequences Within the Vertebrate Hox Clusters Through the Two-Round Whole Genome Duplications Revealed by Phylogenetic Footprinting Analysis

As a result of two-round whole genome duplications, four or more paralogous Hox clusters exist in vertebrate genomes. The paralogous genes in the Hox clusters show similar expression patterns, implying shared regulatory mechanisms for expression of these genes. Previous studies partly revealed the expression mechanisms of Hox genes. However, cis-regulatory elements that control these paralogous gene expression are still poorly understood. Toward solving this problem, the authors searched conserved non-coding sequences (CNSs), which are candidates of cis-regulatory elements. When comparing orthologous Hox clusters of 19 vertebrate species, 208 intergenic conserved regions were found. The authors then searched for CNSs that were conserved not only between orthologous clusters but also among the four paralogous Hox clusters. The authors found three regions that are conserved among all the four clusters and eight regions that are conserved between intergenic regions of two paralogous Hox clusters. In total, 28 CNSs were identified in the paralogous Hox clusters, and nine of them were newly found in this study. One of these novel regions bears a RARE motif. These CNSs are candidates for gene expression regulatory regions among paralogous Hox clusters. The authors also compared vertebrate CNSs with amphioxus CNSs within the Hox cluster, and found that two CNSs in the HoxA and HoxB clusters retain homology with amphioxus CNSs through the two-round whole genome duplications.     

Ciona intestinalis ParaHox genes: evolution of Hox/ParaHox cluster integrity,developmental mode,and temporal colinearity

The Hox gene cluster, and its evolutionary sister the ParaHox gene cluster, pattern the anterior-posterior axis of animals. The spatial and temporal regulation of the genes seems to be intimately linked to the gene order within the clusters. In some animals the tight organisation of the clusters has disintegrated. We note that these animals develop in a derived fashion relative to the norm of their respective lineages. Here we present the genomic organisation of the ParaHox genes of Ciona intestinalis, and note that tight clustering has been lost in evolution. We present a hypothesis that the Hox and ParaHox clusters are constrained as ordered clusters by the mechanisms producing temporal colinearity; when temporal colinearity is no longer needed or used during development, the clusters can fall apart. This disintegration may be mediated by the invasion of transposable elements into the clusters, and subsequent genomic rearrangements.     

The zebrafish genome in context: ohnologs gone missing

Some zebrafish genes appear to lack an ortholog in the human genome and researchers often call them "novel" genes. The origin of many so-called "novel" genes becomes apparent when considered in the context of genome duplication events that occurred during evolution of the phylum Chordata, including two rounds at about the origin of the subphylum Vertebrata (R1 and R2) and one round before the teleost radiation (R3). Ohnologs are paralogs stemming from such genome duplication events, and some zebrafish genes said to be "novel" are more appropriately interpreted as "ohnologs gone missing", cases in which ohnologs are preserved differentially in different evolutionary lineages. Here we consider ohnologs present in the zebrafish genome but absent from the human genome. Reasonable hypotheses are that lineage-specific loss of ohnologs can play a role in establishing lineage divergence and in the origin of developmental innovations. How does the evolution of ohnologs differ from the evolution of gene duplicates arising from other mechanisms, such as tandem duplication or retrotransposition? To what extent do different major vertebrate lineages or different teleost lineages differ in ohnolog content? What roles do differences in ohnolog content play in the origin of developmental mechanisms that differ among lineages? This review explores these questions.     

Cloned sequence repertoires for small- and large-scale biology

How to assign function to the tens of thousands of genes discovered in the chromosomes of a few model species? How to complement the classical genetic approaches that are not always ideally suited to decode complex mechanisms? The solutions to these pressing questions are not simple and rely on the development of novel resources and technologies. Here I critically review what clone collections are available and how they can be exploited for the systematic analysis of gene functions in plants.     

Horizontal gene transfer, genome innovation and evolution

To what extent is the tree of life the best representation of the evolutionary history of microorganisms? Recent work has shown that, among sets of prokaryotic genomes in which most homologous genes show extremely low sequence divergence, gene content can vary enormously, implying that those genes that are variably present or absent are frequently horizontally transferred. Traditionally, successful horizontal gene transfer was assumed to provide a selective advantage to either the host or the gene itself, but could horizontally transferred genes be neutral or nearly neutral? We suggest that for many prokaryotes, the boundaries between species are fuzzy, and therefore the principles of population genetics must be broadened so that they can be applied to higher taxonomic categories.     

Evolutionary conservation of regulated longevity assurance mechanisms

Background

To what extent are the determinants of aging in animal species universal? Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an evolutionarily conserved (public) regulator of longevity; yet it remains unclear whether the genes and biochemical processes through which IIS acts on aging are public or private (that is, lineage specific). To address this, we have applied a novel, multi-level cross-species comparative analysis to compare gene expression changes accompanying increased longevity in mutant nematodes, fruitflies and mice with reduced IIS.

Results

Surprisingly, there is little evolutionary conservation at the level of individual, orthologous genes or paralogous genes under IIS regulation. However, a number of gene categories are significantly enriched for genes whose expression changes in long-lived animals of all three species. Down-regulated categories include protein biosynthesis-associated genes. Up-regulated categories include sugar catabolism, energy generation, glutathione-S-transferases (GSTs) and several other categories linked to cellular detoxification (that is, phase 1 and phase 2 metabolism of xenobiotic and endobiotic toxins). Protein biosynthesis and GST activity have recently been linked to aging and longevity assurance, respectively.

Conclusion

These processes represent candidate, regulated mechanisms of longevity-control that are conserved across animal species. The longevity assurance mechanisms via which IIS acts appear to be lineage-specific at the gene level (private), but conserved at the process level (or semi-public). In the case of GSTs, and cellular detoxification generally, this suggests that the mechanisms of aging against which longevity assurance mechanisms act are, to some extent, lineage specific.     

Mechanisms of genomic imprinting.

A small number of mammalian genes undergo the process of genomic imprinting whereby the expression level of the alleles of a gene depends upon their parental origin. In the past year, attention has focused on the mechanisms that determine parental-specific expression patterns. Many imprinted genes are located in conserved clusters and, although it is apparent that imprinting of adjacent genes is jointly regulated, multiple mechanisms among and within clusters may operate. Recent developments have also refined the timing of the gametic imprints and further defined the mechanism by which DNA methyltransferases confer allelic methylation patterns.     

Birth and death of duplicated genes in completely sequenced eukaryotes

Gene and genome duplications are commonly regarded as being of major evolutionary significance. But how often does gene duplication occur? And, once duplicated, what are the fates of duplicated genes? How do they contribute to evolution? In a recent article, Lynch and Conery analyze divergence between duplicate genes from six eukaryotic genomes. They estimate the rate of gene duplication, the rate of gene loss after duplication and the strength of selection experienced by duplicate genes. They conclude that although the rate of gene duplications is high, so is the rate of gene loss, and they argue that gene duplications could be a major factor in speciation.     

纳他霉素高产菌株Streptomyces gilvosporeus F607基因组及其生物合成基因簇分析

【背景】纳他霉素(Natamycin)是一种天然、广谱、高效的多烯大环内酯类抗真菌剂,褐黄孢链霉菌(Streptomyces gilvosporeus)是一种重要的纳他霉素产生菌。目前S. gilvosporeus基因组序列分析还未有报道,限制了该菌中纳他霉素及其他次级代谢产物合成及调控的研究。【目的】解析纳他霉素高产菌株S. gilvosporeus F607的基因组序列信息,挖掘其次级代谢产物基因资源,为深入研究该菌株的纳他霉素高产机理及生物合成调控机制奠定基础。【方法】利用相关软件对F607菌株的基因组序列进行基因预测、功能注释、进化分析和共线性分析,并预测次级代谢产物合成基因簇;对纳他霉素生物合成基因簇进行注释分析,比较分析不同菌种中纳他霉素生物合成基因簇的差异;分析预测S.gilvosporeusF607中纳他霉素生物合成途径。【结果】F607菌株基因组总长度为8482298bp,(G+C)mol%为70.95%,分别在COG、GO、KEGG数据库提取到5 062、4 428、5063个基因的注释信息。同时,antiSMASH软件预测得到29个次级代谢产物合成基因簇,其中纳他霉素基因簇与S.natalensis、S. chattanoogensis等菌株的纳他霉素基因簇相似性分别为81%和77%。除2个参与调控的sngT和sgnH基因和9个未知功能的orf基因有差异外,S. gilvosporeus F607基因簇中其他纳他霉素生物合成基因及其排列顺序与已知的纳他霉素基因簇高度一致。【结论】分析了S. gilvosporeus全基因组信息,预测了S. gilvosporeus F607中纳他霉素生物合成的途径,为从基因组层面上解析S. gilvosporeus F607菌株高产纳他霉素的内在原因提供了基础数据,为揭示纳他霉素高产的机理及工业化生产和未来新药的发现奠定了良好的基础。     

Small nucleolar RNA genes

Small nucleolar RNAs (snoRNAs) are one of the most numerous and well-studied groups of non-protein-coding RNAs. In complex with proteins, snoRNAs perform the two most common nucleotide modifications in rRNA: 2′-OH-methylation of ribose and pseudouridylation. Although the modification mechanisms and snoRNP structures are highly conserved, the snoRNA genes are surprisingly diverse in organization. In addition to genes transcribed independently, there are genes that are in introns of other genes, form clusters transcribed from a common promoter, or clusters in introns. Interestingly, one type of gene organization usually prevails in different taxa. Vertebrate snoRNAs mostly originate from introns of protein-coding genes; a small group of snoRNAs are encoded by introns of genes for noncoding RNAs.     

Origins and divergence times of mammalian class II MHC gene clusters

The class I and II major histocompatibility complex (MHC) genes are apparently subject to evolution by a birth-and-death process. The rate of gene turnover is much slower in the latter genes than in the former. In placental mammals, the class II region can be subdivided into different orthologous subregions or gene clusters (DR, DQ, DO, and DN), but the origins and evolutionary relationships of these gene clusters are not well established. Here we report the results of our study of the times of origin and evolutionary relationships of these gene clusters in mammals. Our analysis suggests that both class II alpha-chain and beta-chain gene clusters are shared by placental mammals and marsupials, but the gene clusters from nonmammalian species are paralogous to mammalian gene clusters. We estimated the times of divergence between gene clusters in placental mammals using the linearized tree and distance regression methods. Our results indicate that most gene clusters originated 170-200 million years (MY) ago, but that DO beta-chain genes diverged from the other beta-chain gene clusters approximately 210-260 MY ago. The phylogenetic trees for the alpha- and beta-chain genes were not congruent, suggesting that the evolutionary history of the class II gene clusters is more complex than previously thought.