Transposable element-mediated rearrangements are prevalent in human genomes

Abstract

Transposable elements constitute about half of human genomes, and their role in generating human variation through retrotransposition is broadly studied and appreciated. Structural variants mediated by transposons, which we call transposable element-mediated rearrangements (TEMRs), are less well studied, and the mechanisms leading to their formation as well as their broader impact on human diversity are poorly understood. Here, we identify 493 unique TEMRs across the genomes of three individuals. While homology directed repair is the dominant driver of TEMRs, our sequence-resolved TEMR resource allows us to identify complex inversion breakpoints, triplications or other high copy number polymorphisms, and additional complexities. TEMRs are enriched in genic loci and can create potentially important risk alleles such as a deletion in TRIM65, a known cancer biomarker and therapeutic target. These findings expand our understanding of this important class of structural variation, the mechanisms responsible for their formation, and establish them as an important driver of human diversity.

Dynamics of transposable element accumulation in the non-recombining regions of mating-type chromosomes in anther-smut fungi

“…TE copies thereby accumulating at the margin of the non-recombining regions may impact their evolution (Maloisel & Rossignol, 1998; Ben-Aroya et al ., 2004; Yelina et al ., 2012; Kent et al ., 2017). TEs can trigger chromosomal rearrangements (Balachandran et al ., 2022), and they recruit silencing marks, such as DNA methylation and heterochromatin formation, that can suppress recombination (Maloisel & Rossignol, 1998; Ben-Aroya et al ., 2004; Yelina et al ., 2012, 2015; Bachtrog, 2013; Li et al ., 2016; Kent et al ., 2017). TEs can also induce deleterious mutations, which can select for recombination suppression that ensures the sheltering of the genetic load they create (Jay et al ., 2022).…”

“…However, TE activity of replication and insertion is generally deleterious to its host genome (Payer & Burns, 2019; Andrenacci et al ., 2020; Burns, 2020). Their insertions can indeed disrupt gene coding or regulatory sequences (Hancks & Kazazian, 2016), induce epigenetic changes (Castanera et al ., 2016; Choi & Lee, 2020) or promote chromosomal rearrangements via ectopic recombination between non-allelic TE copies (Lim & Simmons, 1994; Han et al ., 2008; Ade et al ., 2013; Bennetzen & Wang, 2014; Balachandran et al ., 2022). TEs can also incur a substantial replication cost as they can represent a large proportion of the genome (Schnable et al ., 2009).…”