9 Zeh Transposable elements and an epigenetic basis for punctuated equilibria
BE 31 715
Evolution is frequently concentrated in bursts of rapid morphological change and speciation followed by long term stasis. We propose that this pattern of punctuated equilibria results from an evolutionary tug-of-war between host genomes and transposable elements (TEs) mediated through the epigenome.
*Epigenetic regulatory mechanisms (RNA interference, DNA methylation and histone modifications) maintain stasis by suppressing TE mobilization. However, physiological stress disrupts epigenetic regulation and unleashes TEs.
* DNA transposons apparently diverged into 10 of 12 superfamilies(30) in the common ancestor of eukaryotes.(31) Retrotransposons are similarly ancient LTRs, LINEs, SINEs, Dicty intermediate repeat sequence (DIRS) 32). Eukaryotes have been coevolving antagonistically with TEs (33) TEs are highly mutagenic, accounting for 50\% of deleterious mutations in Drosophila(34) and 10\% in mice.(35) In non-coding regions, TE insertions can undermine genomic integrity by acting as foci for unequal homologs recombination, resulting in duplications, deletions and translocations.(37)
*Fundamental mechanisms of epigenetic regulation (RNAi, histone modifications and DNA methylation) arose as a defense against TEs. Key elements (Argonaute, Piwi-like protein, Dicer-like protein and RNA-dependent RNA polymerase) suggests that the common ancestor possessed a sophisticated silencing system involving siRNAs).(38,39)
*To effectively defend against nucleic acid parasites, a cell must distinguish its own transcriptionally active genes from those of mobile elements. Genomic self/non-self recognition derives from small RNA/protein complexes.(40) [outline of mechanisms here]
*Disruption of any of these silencing processes may dramatically increase TE expression and mobilization, often with catastrophic consequences for host fitness. In At, mutations in the chromatin remodeling gene ddm1 result in a 20-fold increase in transposition of the DNA transposon AtMu1.(42) In Mm, the gene Maelstrom (Mael) encodes a protein that interacts with the piRNA pathway in the nuage,(43) a perinuclear structure involved in RNAi-mediated gene regulation in the germ line of animals.(43) Knockout of Mael resulted in demethylation of LINE-1 TEs and a 100-fold increase in the production of LINE-1 ribonucleoproteins in germ cells of Mael -/- males.(44) Accumulation of LINE-1 ribonucleoproteins was associated with extensive DNA damage, defective synapsis, meiotic arrest and male sterility.(44, Dnmt3L 45) In Dm, loss-of-function alleles of Mael and other nuage component genes also exhibit LINE de-repression, in this case, in ovarian tissue, resulting in female sterility.(46)
* In mammals, global demethylation occurs during preimplantation embryonic development and coincides with dramatic increases in TE expression.(54)
*A similar pattern occurs during the early stages of germcell development when the methylation marks required for genomic imprinting are reset. Developmentally regulated demethylation thus enables TEs to escape from transcriptional repression during critical stages and cause heritable transposition mutations.(55,56)
*Examples of new genes and regulatory elemetns due to TE.
* SINE insertions are highly informative markers in rapidly evolving lineages precisely because it is TE mobilization that triggers bursts of evolution, with some fraction of SINE insertions playing a role in the colonization of new fitness peaks.
*Seehausen(106) showed that the propensity for diversification increased along a single branch of the cichlid phylogeny, a lineage of haplochromine cichlids. As predicted by the epi-transposon hypothesis, analysis of 75 SINE loci indicates that this haplochromine lineage has experienced repeated bouts of cichlid-specific SINE insertions followed by extensive radiations within each lake.(108)