The effect of stress on genome regulation and structure

Abstract

Background: Stresses exert evolutionary pressures on all organisms, which have developed sophisticated responses to cope and survive. These responses involve cellular physiology, gene regulation and genome remodelling.

Scope: In this review, the effects of stress on genomes and the connected responses are considered. Recent developments in our understanding of epigenetic genome regulation, including the role of RNA interference (RNAi), suggest a function for this in stress initiation and response. We review our knowledge of how different stresses, tissue culture, pathogen attack, abiotic stress, and hybridization, affect genomes. Using allopolyploid hybridization as an example, we examine mechanisms that may mediate genomic responses, focusing on RNAi-mediated perturbations.

Conclusions: A common response to stresses may be the relaxation of epigenetic regulation, leading to activation of suppressed sequences and secondary effects as regulatory systems attempt to re-establish genomic order.

Fig. 1.

Left: generalized RNAi pathway. Double-stranded RNA (dsRNA) produced, for example, by convergent transcription, serves as a substrate for the enzyme Dicer, which cuts dsRNA molecules into short (approx. 21–22 nucleotide long) fragments. An RNA-dependent RNA polymerase (RdRP) amplifies these small RNAs. The RNAi silencing complex (RISC) contains the ARGONAUTE (AGO) protein, mediates the annealing of the small RNA strands to the cognate mRNA and induces degradation or blocks translation. Right: action of RNAi on DNA. A specialized RISC complex (RITS) (Verdel et al., 2004) targets loci homologous to small RNAs for epigenetic suppression, presumably through recognition of DNA sequence or of nascent RNA, leading to recruitment of histone methylases, which add methyl groups to lysine residues (in particular in positions K9 and K27) on histone 3 (H3). Methylated H3K9 may recruit heterochromatin protein 1 or DNA methylases, which transfer methyl groups to the DNA and ultimately lead to heterochromatin formation. CH3 (inverted): methylated DNA; CH3 (right way up): methylated histones.

Fig. 2.

Arrangements of long terminal repeat (LTR) retrotransposons and possible effects. LTRs can function as promoters or enhancers and drive expression not only of the associated retrotransposon genes, but also of adjacent genes. Transcription, indicated by the grey arrows, leads to synthesis of complementary RNAs, which anneal forming double-stranded RNA (dsRNA) and trigger RNAi initiation. (A) Two LTR retrotransposons are positioned in a head-to-head configuration and read-through RNAs of both elements result in dsRNA. (B) An LTR retrotransposon is inserted inside another causing the formation of partially overlapping complementary transcripts. (C) Inverted repeat formed by an LTR retrotransposon leading to an RNA with internal complementarity (hairpin). (D) A solo-LTR inside the intron of a gene. Solo LTRs are remnants of retrotransposons that have ‘lost’ the rest of their element. Similar scenarios have been observed in wheat (Kashkush et al., 2003).

Fig. 3.

Three hypothetical examples of parental incompatibilities. (A) The cytoplasm of the egg-parent (species E) contributes a microRNA specific for a paternally expressed transposon. The intraspecific cross leads to RNAi. In the cross of the egg-parent (species E) to a different species (G) the lack of a microRNA specific to a transposon expressed in the G parent prevents transposon suppression, triggering genomic instability. (B) A multi-protein complex involved in heterochromatic regulation has diverged since the separation of two species from a common ancestor. In intraspecific crosses all protein subunits are compatible. In interspecific crosses productive and unproductive assemblies take place depending on the random combination of protein subunits. If these complexes act at very low concentration inside the cell, their activity would vary stochastically in meristematic cells, in some reaching a critical threshold for activity and producing different imprinted states. (C) Genes encoding the subunits of the same complex illustrated in B have diverged in expression between species A and species G. Species G expresses higher amounts of the blue subunit and lower amounts of the green and brown subunits. In the hybrid, the excess of blue subunit titrates the substoichiometric amounts of green and brown subunits inactivating the complex.

Fig. 4.

Hypothetical genome regulation under normal and stress conditions. Under normal conditions heterochromatin maintenance mechanisms repress transcription of repetitive DNA (left). Stress can cause the relaxation of epigenetic imprints. RNAi and other heterochromatin maintenance pathways fail, resulting in the activation of transposons (right). If the shock does not lead to death the cell undergoes a stochastic remodelling of its genome resulting in altered epigenetic marks and in novel gene expression. CH3 (inverted): methylated DNA; CH3 (right way up): methylated histones.