A role for epigenetics in adaptative evolution (original) (raw)
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Chromosomal histone modification patterns – from conservation to diversity
Trends in Plant Science, 2006
The organization of DNA into chromatin regulates expression and maintenance (replication, repair, recombination, segregation) of genetic information in a dynamic manner. The N-terminal tails of the nucleosomal core histones are subjected to post-translational modifications such as acetylation, methylation, phosphorylation, ubiquitination, glycosylation, ADP-ribosylation, carbonylation and sumoylation. These modifications, together with DNA methylation, control the folding of the nucleosomal array into higher order structures and mediate signalling for cellular processes. Although histones and their modifications are highly conserved, recent data show that chromosomal distribution of individual modifications (acetylation, methylation, phosphorylation) can differ along the cell cycle as well as among and between groups of eukaryotes. This implies the possibility of evolutionary divergence in reading the 'histone code'.
Oikos, 2010
Epigenetics, the science of heritable but modifiable information, is now a well accepted component of many research fields. Nevertheless, epigenetics has not yet found broad appreciation in one of the most exciting fields of biology: the comprehension of evolution. This is surprising, since the reason for the existence of this alternative informationtransmitting system lies certainly in the evolutionary advantage it provides. Theoretical considerations support a model in which epigenetic mechanisms allow for increasing phenotypic variability and permit populations to explore the adaptive landscape without modifications of the genotype. The data presented here support the view that modulating the epigenotype of the human bloodfluke Schistosoma mansoni by treatment of larvae with histone deacetylase inhibitor leads indeed to an increase of phenotypic variability. It is therefore conceivable that environmentally induced changes in the epigenotype release new phenotypes on which selection can act and that this process is the first step in adaptive evolution.
Histone Methylome of the Human Parasite Schistosoma Mansoni
RNA Technologies
The trematode Schistosoma mansoni belongs to the group of digenetic parasites which need obligatory multiple hosts to develop. They transit between hosts as free-swimming stages in fresh water ecosystems. They generate phenotypically different developmental stages throughout their lifecycle and receive hugly heterogenous environmental cues. Each developmental stage is characterized by specific posttranslational histone modifications, in particular methylations. The combination of the different marks result in stage specific chromatin structure that is essential for development, sexual biology and pathogenesis. Histone methylation also responds to environmental changes and seems to be involved in an adaptive reponse or adjustment to the environment. Histone methylation thus represent promising source of therapeutic targets. In this chapter we will present the state-ofthe-art of how the dynamics of histone methylation are involved in multiple factors of the schistosome's development, as well as what is still lacking for better understanding it.
Quantitative chromatin immunoprecipitation (Q-ChIP) applied to Schistosoma mansoni
Molecular and Biochemical Parasitology, 2009
The life-cycle of the platyhelminth parasite Schistosoma mansoni is characterized by marked morphological changes between the various stages that are the result of a complex developmental program. In order to study the role of epigenetic mechanisms in regulating this program, and more particularly the role of changes in histone modifications in the control of the transcription of key genes, we have adapted the technique of quantitative chromatin immunoprecipitation (Q-ChIP) to larval stages and adult worms. We have used the classical method involving formaldehyde-induced cross-linking of DNA-associated proteins, followed by ultrasonication to fragment the DNA before immunoprecipitation and have established a protocol for use with schistosomes. We show, using antibodies directed against acetylated histone H4, that the technique is applicable to the parasite and allows the quantification and comparison of the levels of modified histone at gene promoters at different life-cycle stages.
Epigenetic control of gene function in schistosomes: a source of therapeutic targets?
Frontiers in Genetics, 2014
The discovery of the epigenetic regulation of gene expression has revolutionized both our understanding of how genomes function and approaches to the therapy of numerous pathologies. Schistosomes are metazoan parasites and as such utilize most, if not all the epigenetic mechanisms in play in their vertebrate hosts: histone variants, histone tail modifications, non-coding RNA and, perhaps, DNA methylation. Moreover, we are acquiring an increasing understanding of the ways in which these mechanisms come into play during the complex schistosome developmental program. In turn, interest in the actors involved in epigenetic mechanisms, particularly the enzymes that carry out epigenetic modifications of histones or nucleic acid, as therapeutic targets has been stimulated by the finding that their inhibitors exert profound effects, not only on survival, but also on the reproductive function of Schistosoma mansoni. Here, we review our current knowledge, and what we can infer, about the role of epigenetic mechanisms in schistosome development, differentiation and survival. We will consider which epigenetic actors can be targeted for drug discovery and what strategies can be employed to develop potent, selective inhibitors as drugs to cure schistosomiasis.
Molecular and Biochemical Parasitology, 2009
Histone modifications are important epigenetic marks that influence chromatin structure and consequently play a role in the control of eukaryotic transcription. Several histone modifying enzymes have been characterized in Schistosoma mansoni and it has been suggested that the regulation of gene transcription in schistosomes may require the action of these enzymes. However, the influence of chromatin structure on gene transcription in schistosomes has never been investigated. Chromatin immunoprecipitation (ChIP) is the technique of choice to study the relationship between histone modifications and gene expression. Although this technique has been widely used with cultured cells from model organisms and with many unicellular organisms, it remains challenging to apply this technique to non-conventional organisms that undergo complex life cycles. In this work, we describe a native ChIP procedure that is applicable to all the stages of the S. mansoni life cycle and does not require expensive equipment. Immunoprecipitated DNA was analysed on a whole-genome scale using massively parallel sequencing (ChIP-Sequencing or ChIP-Seq). We show that ChIP-Seq and conventional quantitative PCR deliver comparable results for a life-cycle regulated locus, smRHO, that encodes a guanine-protein coupled receptor. This is the first time that the ChIP-Seq procedure has been applied to a parasite. This technique opens new ways for analyzing epigenetic mechanisms in S. mansoni at a whole-genome scale and on the level of individual loci.
The class I histone deacetylases of the platyhelminth parasite Schistosoma mansoni
Biochemical and Biophysical Research Communications, 2008
Histone deacetylases (HDAC) form a conserved enzyme family that control gene expression via the removal of acetyl residues from histones and other proteins and are under increasing investigation as therapeutic targets, notably in cancer and parasitic diseases. To investigate the conservation of these enzymes in the platyhelminth parasite Schistosoma mansoni, we cloned and characterized three class I HDACs, orthologues of mammalian HDAC1, 3 and 8, and confirmed their identities by phylogenetic analysis. The identification of an HDAC8 orthologue showed that it is not vertebrate-specific as previously thought and insertions in its catalytic domain suggest specific enzymatic properties. SmHDAC1, 3, and 8 mRNAs are expressed at all schistosome life-cycle stages. SmHDAC1 repressed transcriptional activity in a mammalian cell line and this activity was dependent on its catalytic activity since transcription was partially restored by treatment with trichostatin A and a catalytic site mutant failed to repress transcription.