Bergerac strains of Caenorhabditis elegans revisited: expansion of Tc1 elements imposes a significant genomic and fitness cost

Abstract

The DNA transposon Tc1 was the first transposable element (TE) to be characterized in Caenorhabditis elegans and to date, remains the best-studied TE in Caenorhabditis worms. While Tc1 copy-number is regulated at approximately 30 copies in the laboratory Bristol N2 and the vast majority of C. elegans strains, the Bergerac strain and its derivatives have experienced a marked Tc1 proliferation. Given the historical importance of the Bergerac strain in the development of the C. elegans model, we implemented a modern genomic analysis of three Bergerac strains (CB4851, RW6999, and RW7000) in conjunction with multiple phenotypic assays to better elucidate the (i) genomic distribution of Tc1, and (ii) phenotypic consequences of TE deregulation for the host organism. The median estimates of Tc1 copy-number in the Bergerac strains ranged from 451 to 748, which is both (i) greater than previously estimated, and (ii) likely to be an underestimate of the actual copy-numbers since coverage-based estimates and ddPCR results both suggest higher Tc1 numbers. All three Bergerac strains had significantly reduced trait means compared to the N2 control for each of four fitness-related traits, with specific traits displaying significant differences between Bergerac strains. Tc1 proliferation was genome-wide, specific to Tc1, and particularly high on chromosomes V and X. There were fewer Tc1 insertions in highly expressed chromatin environments than expected by chance. Furthermore, Tc1 integration motifs were also less frequent in exon than non-coding sequences. The source of the proliferation of Tc1 in the Bergerac strains is specific to Tc1 and independent of other TEs. The Bergerac strains contain none of the alleles that have previously been found to derepress TE activity in C. elegans. However, the Bergerac strains had several Tc1 insertions near or within highly germline-transcribed genes which could account for the recent germline proliferation.

Activity and Silencing of Transposable Elements in C. elegans

“…However, in some other isolates of C. elegans, such as the Bergerac strain, transposons do jump in germline cells. These isolates can have highly increased copy numbers of transposons, with up to 748 Tc1 elements in the Bergerac strain [26]. The most active transposons identified in such strains, as well as in strains with mutator mutations isolated in screens for transposon activation, are the related transposons Tc1 and Tc3 [27], which are present in 32 and 22 copies, respectively, in the Bristol strain genome (Table 1).…”

“…Although Tc1 and Tc3 insert into TA dinucleotides, the sequences immediately flanking the TA affect the target choice [55][56][57]. On the level of the chromosomes, the Tc1 elements jump from and into all chromosomes, but reside in regions of repressed chromatin and are underrepresented in domains with highly active chromatin marks [26]. In general, DNA transposons are found on the autosomal chromosome arms of C. elegans [3,57].…”

Activity and Silencing of Transposable Elements in C. <em>elegans</em>

“…However, in other isolates of C. elegans, such as Bergerac, transposons do jump in germline cells. These isolates can have highly increased copy numbers of transposons with up to 748 Tc1 elements in Bergerac [26]. The most active transposons identified in such strains as well as in strains with mutator mutations isolated in screens for transposon activation, are the related transposons Tc1 and Tc3 present in 32 and 22 copies respectively in the Bristol genome (Table I).…”

Reproducible evaluation of transposable element detectors with McClintock 2 guides accurate inference of Ty insertion patterns in yeast

“…Despite these issues, one emerging theme from current evaluation studies is that considerable variation in performance exists among different short-read TE detectors, across organisms and evaluation frameworks [8, 14, 15, 16]. As such, there is not yet any clear basis to select the best short-read TE detector for a new organism, and thus researchers must base tool choice by extrapolation from performance on other taxa or employ multiple methods to ensure robust biological conclusions [17, 18, 19].…”

“…The original McClintock system automated installation of these six “component” TE detection methods, provided a common interface to run all components, reduced the number of shared input files, and generated a standard set of output files [15]. Since its initial development, the McClintock system has been used to support detection of TE insertions and enable biological discoveries in a variety of organisms and biological contexts [15, 16, 17, 18, 19, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44] and to facilitate comparative evaluation of multiple TE detectors [15, 16, 45].…”