DNA methylation and structural and functional bimodality of vertebrate promoters

Human promoters divide into 2 classes, the low CpG (LCG) and the high CpG (HCG), based on their CpG dinucleotide content. The LCG class of promoters is hypermethylated and is associated with tissue-specific genes, whereas the HCG class is hypomethylated and associated with broadly expressed genes. By analyzing several chordate genomes separated for hundreds of millions of years, here we show that the divide between low CpG and high CpG promoters is conserved in several distantly related vertebrate taxa (including human, chicken, frog, lizard, and fish) but not in close invertebrate outgroups (sea squirts). Furthermore, LCG and HCG promoters are distinctively associated with tissue-specific and broadly expressed genes in these distantly related vertebrate taxa. Our results indicate that the function of DNA methylation on gene expression is conserved across these vertebrate taxa and suggest that the 2 classes of promoters have evolved early in vertebrate evolution, as a consequence of the advent of global DNA methylation.     

Comparative analyses of DNA methylation and sequence evolution using Nasonia genomes

The functional and evolutionary significance of DNA methylation in insect genomes remains to be resolved. Nasonia is well situated for comparative analyses of DNA methylation and genome evolution, since the genomes of a moderately distant outgroup species as well as closely related sibling species are available. Using direct sequencing of bisulfite-converted DNA, we uncovered a substantial level of DNA methylation in 17 of 18 Nasonia vitripennis genes and a strong correlation between methylation level and CpG depletion. Notably, in the sex-determining locus transformer, the exon that is alternatively spliced between the sexes is heavily methylated in both males and females, whereas other exons are only sparsely methylated. Orthologous genes of the honeybee and Nasonia show highly similar relative levels of CpG depletion, despite ~190 My divergence. Densely and sparsely methylated genes in these species also exhibit similar functional enrichments. We found that the degree of CpG depletion is negatively correlated with substitution rates between closely related Nasonia species for synonymous, nonsynonymous, and intron sites. This suggests that mutation rates increase with decreasing levels of germ line methylation. Thus, DNA methylation is prevalent in the Nasonia genome, may participate in regulatory processes such as sex determination and alternative splicing, and is correlated with several aspects of genome and sequence evolution.     

Genome-wide and single-base resolution DNA methylomes of the Pacific oyster Crassostrea gigas provide insight into the evolution of invertebrate CpG methylation

Background

Studies of DNA methylomes in a wide range of eukaryotes have revealed both conserved and divergent characteristics of DNA methylation among phylogenetic groups. However, data on invertebrates particularly molluscs are limited, which hinders our understanding of the evolution of DNA methylation in metazoa. The sequencing of the Pacific oyster Crassostrea gigas genome provides an opportunity for genome-wide profiling of DNA methylation in this model mollusc.

Results

Homologous searches against the C. gigas genome identified functional orthologs for key genes involved in DNA methylation: DNMT1, DNMT2, DNMT3, MBD2/3 and UHRF1. Whole-genome bisulfite sequencing (BS-seq) of the oyster’s mantle tissues revealed that more than 99% methylation modification was restricted to cytosines in CpG context and methylated CpGs accumulated in the bodies of genes that were moderately expressed. Young repeat elements were another major targets of CpG methylation in oysters. Comparison with other invertebrate methylomes suggested that the 5’-end bias of gene body methylation and the negative correlation between gene body methylation and gene length were the derived features probably limited to the insect lineage. Interestingly, phylostratigraphic analysis showed that CpG methylation preferentially targeted genes originating in the common ancestor of eukaryotes rather than the oldest genes originating in the common ancestor of cellular organisms.

Conclusions

Comparative analysis of the oyster DNA methylomes and that of other animal species revealed that the characteristics of DNA methylation were generally conserved during invertebrate evolution, while some unique features were derived in the insect lineage. The preference of methylation modification on genes originating in the eukaryotic ancestor rather than the oldest genes is unexpected, probably implying that the emergence of methylation regulation in these ''relatively young’ genes was critical for the origin and radiation of eukaryotes.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1119) contains supplementary material, which is available to authorized users.     

Myxosporea (Myxozoa,Cnidaria) Lack DNA Cytosine Methylation

DNA cytosine methylation is central to many biological processes, including regulation of gene expression, cellular differentiation, and development. This DNA modification is conserved across animals, having been found in representatives of sponges, ctenophores, cnidarians, and bilaterians, and with very few known instances of secondary loss in animals. Myxozoans are a group of microscopic, obligate endoparasitic cnidarians that have lost many genes over the course of their evolution from free-living ancestors. Here, we investigated the evolution of the key enzymes involved in DNA cytosine methylation in 29 cnidarians and found that these enzymes were lost in an ancestor of Myxosporea (the most speciose class of Myxozoa). Additionally, using whole-genome bisulfite sequencing, we confirmed that the genomes of two distant species of myxosporeans, Ceratonova shasta and Henneguya salminicola, completely lack DNA cytosine methylation. Our results add a notable and novel taxonomic group, the Myxosporea, to the very short list of animal taxa lacking DNA cytosine methylation, further illuminating the complex evolutionary history of this epigenetic regulatory mechanism.     

DNA methylation with a sting: an active DNA methylation system in the honeybee

The existence of DNA methylation in insects has been a controversial subject over a long period of time. The recently completed genome sequence of the honeybee Apis mellifera has revealed the first insect with a full complement of DNA methyltransferases. A parallel study demonstrated that these enzymes are catalytically active and that Apis genes can be methylated in specific patterns. These findings establish bees as a model to analyze the function of DNA methylation systems in invertebrate organisms and might also be important to understand evolutionary aspects of DNA methylation in higher eukaryotes.     

Hox基因及其在海胆中的研究进展

Hox(homeobox genes)基因是存在于染色体上的一段高度保守序列,其蛋白产物作为转录因子也是高度保守的。这些基因调节胚胎发育,尤其在脊椎动物前-后轴(antero-posterior axis)的发育过程中起着重要作用,并指导脊椎动物的体型形成。海胆是海洋中一类比较常见的无脊椎动物和主要的海水养殖动物,它的Hox基因对它动-植物轴(animal-vegetalaxis)的形成有调控作用,并对进化研究和养殖生产具有重要意义。综述了近年来Hox基因在海胆中的研究进展。