Computational analysis and characterization of UCE-like elements (ULEs) in plant genomes

Abstract

Ultraconserved elements (UCEs), stretches of DNA that are identical between distantly related species, are enigmatic genomic features whose function is not well understood. First identified and characterized in mammals, UCEs have been proposed to play important roles in gene regulation, RNA processing, and maintaining genome integrity. However, because all of these functions can tolerate some sequence variation, their ultraconserved and ultraselected nature is not explained. We investigated whether there are highly conserved DNA elements without genic function in distantly related plant genomes. We compared the genomes of Arabidopsis thaliana and Vitis vinifera; species that diverged~115 million years ago (Mya). We identified 36 highly conserved elements with at least 85% similarity that are longer than 55 bp. Interestingly, these elements exhibit properties similar to mammalian UCEs, such that we named them UCE-like elements (ULEs). ULEs are located in intergenic or intronic regions and are depleted from segmental duplications. Like UCEs, ULEs are under strong purifying selection, suggesting a functional role for these elements. As their mammalian counterparts, ULEs show a sharp drop of A+T content at their borders and are enriched close to genes encoding transcription factors and genes involved in development, the latter showing preferential expression in undifferentiated tissues. By comparing the genomes of Brachypodium distachyon and Oryza sativa, species that diverged~50 Mya, we identified a different set of ULEs with similar properties in monocots. The identification of ULEs in plant genomes offers new opportunities to study their possible roles in genome function, integrity, and regulation.

Ultraconserved Elements Occupy Specific Arenas of Three-Dimensional Mammalian Genome Organization

“…These findings tying UCEs to genome organization are especially intriguing in light of the proposal that UCEs may contribute to genome integrity through yet another potent organizational feature of genomes—allelic and homolog pairing (Chiang et al, 2008; Derti et al, 2006; Kritsas et al, 2012; McCole et al, 2014; Vavouri et al, 2007). Indeed, they raise the question of whether UCEs contribute to the establishment of domains, and/or whether the evolution of a domain promotes the fixation of UCEs within the domain.…”

“…While UCEs have been found to encompass a variety of functions, including enhancer, promoter, splicing, and repressive activities (Bejerano et al, 2004; Dickel et al, 2018; Kushawah and Mishra, 2017;Pennacchio et al, 2006; Poitras et al, 2010; Sandelin et al, 2004; Warnefors et al, 2016), these functions arguably fall short of explaining ultraconservation, per se. We have suggested that UCEs may maintain their sequence conservation through a mechanism involving the pairing and comparison of allelic UCEs, followed by loss of fitness should mutations or rearrangements that disrupt UCE pairing be detected (Chiang et al, 2008; Derti et al, 2006; McCole et al, 2014) (see also Elgar and Vavouri, 2008; Kritsas et al, 2012). Such a mechanism would protect genome integrity in the body overall and, at the organ-ismal level, promote ultraconservation over evolutionary timescales.…”

The Most Deeply Conserved Noncoding Sequences in Plants Serve Similar Functions to Those in Vertebrates Despite Large Differences in Evolutionary Rates

“…While they found 489 syntenic LIMEs in animal genomes with 100% identity over 200 bp, they did not find a single syntenic LIME in plants (100% identity over 100 bp). Using less stringent conditions (85% identity over 56 bp), Kritsas et al (2012) found CNSs between Arabidopsis and grape; however, every CNS found was within 2 kb of its gene.…”

“…This is largely due to their algorithm being limited to the 2-kb 59 upstream region of Arabidopsis genes. Using whole-genome BLAST searches between Arabidopsis and grape, Kritsas et al (2012) identified 29 orthologous hits with at least 85% identity over a span of 56 bp or more. Only three of the ultraconserved-like elements (ULEs) overlap deep CNSs.…”

Chromatin and epigenetic features of long-range gene regulation

“…Since their original discovery in vertebrate genomes, CNEs were found around orthologous genes in other metazoa (54) and recently in plants (55,56). With extremely rare exceptions (26), none of these CNEs in Drosophila or C aenorhabditis elegans are similar at sequence level to any of the vertebrate CNEs, suggesting the existence of equivalent elements in the common ancestor followed by parallel, slow turnover in independent lineages.…”