Epigenomics and TE Evolution

Epigenetics has revolutionized our understanding of gene regulation, yet remarkably little is known about how epigenetic marks, such as small RNA (sRNA), DNA methylation, and histone modifications, evolve within and between populations.AthChr1TEGE

My work in this area has mainly been focused on inferring the evolutionary impact of epigenetic silencing of transposable element (TE) insertions in the genome of the model plant Arabidopsis thaliana, and a close relative, A. lyrata. TEs are selfish genetic elements that populate the genomes of virtually all eukaryotic species. To ensure their persistence, TEs increase in copy number at a cost to the fitness of their hosts. ATEGElabelccordingly, host organisms have evolved defense mechanisms that silence, or render inactive, individual TE copies. In plants, this is achieved in part by methylation of the TE sequences, which prevents their transcription.

My work (Ref 2) suggests that silencing of TEs by sRNA-directed DNA methylation, which has the well-described benefit of preventing the proliferation of harmful new insertions, can also impose a cost when TEs are inserted near genes. This is because silencing of these TEs can also perturb the expression of nearby genes. This has been shown for specific loci, but my work suggests that it is a genome-wide phenomenon, and may lead to stronger selection against methylated TE insertions near genes and their preferential loss from gene dense regions of chromosomes. Because of this, it may be useful to think of epigenetic silencing of TEs as an evolutionary tradeoff.Tradeoff

In collaboration with Detlef Weigel’s group at the Max Planck Institute for Developmental Biology, I examined variation in transposable element (TE) content and 24-nt small RNA (sRNA) between Arabidopsis thaliana and Arabidopsis lyrata (Ref 7). These two species are separated by 10 million years of evolution, and exhibit large differences in genome size (A. lyrata > A. thaliana), chromosome number (8 vs 5), and TE copy number (A. lyrata > A. thaliana).

We examined gene expression levels at ~20,000 orthologs between the two species, and found that genes that differed in the presence of a proximal TE insertion (and especially a sRNA targeted TE) consistently had divergent gene expression patterns compared to the genome-wide average. Importantly, the direction of this difference was consistent with co-regulation of TEs and nearby genes by sRNA-directed DNA methylation.

My future work will aim to understand the evolutionary forces that shape epigenetic diversity in populations since divergence from a common ancestor. I will begin by extending my work on the evolutionary impact of epigenetic silencing of TEs. This work will combine analysis of next generation sequencing data, molecular genetic analysis, and exploration of theoretical models of evolutionary epigenomics.