Transposition favors the generation of large effect mutations that may facilitate rapid adaption

Abstract

Transposable elements (TEs) are mobile parasitic sequences that have been repeatedly coopted during evolution to generate new functions and rewire gene regulatory networks. Yet, the contribution of active TEs to the creation of heritable mutations remains unknown. Using TE accumulation lines in Arabidopsis thaliana we show that once initiated, transposition produces an exponential spread of TE copies, which rapidly leads to high mutation rates. Most insertions occur near or within genes and targets differ between TE families. Furthermore, we uncover an essential role of the histone variant H2A.Z in the preferential integration of Ty1/copia retrotransposons within environmentally responsive genes and away from essential genes. We also show that epigenetic silencing of new Ty1/copia copies can affect their impact on major fitness-related traits, including flowering time. Our findings demonstrate that TEs are potent episodic (epi)mutagens that, thanks to marked chromatin tropisms, limit the mutation load and increase the potential for rapid adaptation.

Fig. 1

TE insertions accumulate in the epiRILs. a Crossing scheme used to generate the epiRIL population. b Sequencing alignment tracks for epiRIL 394 and Col-0. Concordant and discordant mate-pair reads, as well as the sense or antisense orientation for the latter, are indicated in gray, brown and cyan, respectively c Number and identity of insertions accumulated in wild-type, ddm1 and the epiRILs. Number of hemizygous insertions are indicated in brackets. Pie charts show the proportion of insertions matching different full-length reference TE sequences. d (epi)QTL mapping of the number of insertions produced by ATCOPIA93, VANDAL21, and ATENSPM3. The full-length reference TE sequence located within the single (epi)QTL interval in each case is indicated. Box-plots indicate the variation in the number of insertions in the epiRILs in relation to the parental origin of the relevant (epi)QTL interval. For each boxplot, the lower and upper bounds of the box indicate the first and third quartiles, respectively, and the center line indicates the median. Source data of Figs. 1b and 1c are provided as a Source Data file

Fig. 2

Transposition follows a chain reaction in the epiRILs. a Dynamics of insertion accumulation for the three TE families. Observed data obtained at F8 and F9 for ten epiRILs is shown for epiRILs harboring new private insertions. b Average rate across generations of TE-induced (black line) and small size mutations (red line) obtained using the epiRILs and MA lines, respectively (bottom panels). Gray area represents 95% C.I. Transposition and excision rates per copy per generation, as well as TE copy number (CN) required for triggering concerted epigenetic silencing are indicated

Fig. 3

TEs exhibit strong and diverse chromatin-associated insertion biases towards genes. a Circos representation of private TE insertions detected for VANDAL21, ATENSPM3, and ATCOPIA93 within wild-type intervals. Centromere positions are indicated by black dots. b Fraction of TE insertions in genes, TEs and intergenic regions. c Fraction of essential genes among genes targeted by VANDAL21, ATENSPM3 or ATCOPIA93 in the epiRILs. Statistical significance for each comparison was obtained using the Chi-square test. d Metagene analysis showing the distribution of new insertions. e Relative abundance of insertion sites in relation to the nine chromatin states defined in A. thaliana. f Levels of DNAse hypersensitivity (DH; top panel), H3K7me3 (middle panel), and H2A.Z (bottom panel) around VANDAL21, ATENSPM3, and ATCOPIA93 insertion sites, respectively. Source data are provided as a Source Data file

Fig. 4

H2A.Z guides the integration of Ty1/Copia retrotransposons. a Experimental strategy for determining the role of H2A.Z in the integration of ATCOPIA93. b Number of new ATCOPIA93 insertions detected in HTA9 HTA11 and hta9 hta11 F3 seedlings (top). Fraction of essential genes among those targeted by ATCOPIA93 (bottom). Statistically significant differences were calculated using the chi-square test. c Meta-analysis of levels of H2A.Z levels around ATCOPIA93 insertion sites. d Density of ATCOPIA93 insertions over well positioned nucleosomes. e Phylogenetic analysis of Tos17, Ty1 and 110A. thaliana Ty1/Copia LTR-retrotransposons. f Experimental strategy for studying transposition of the heat-responsive ATCOPIA78 LTR-retrotransposon in A. thaliana. g Number of new ATCOPIA78 insertions detected in F1 seedlings of nrpd1 plants grown under control or heat-stress conditions. h Meta-analysis of A. thaliana, rice (O. sativa) and yeast (S. cerevisiae) H2A.Z levels around ATCOPIA78, Tos17, and Ty1 insertion sites, respectively. For A. thaliana, experimental and natural insertions are indicated by solid and dotted lines, respectively. Source data of Figure panels. b, d, g, and h are provided as a Source Data file

Fig. 5

ATCOPIA preferentially targets environmentally responsive genes. a GO term analysis of genes with ATCOPIA93 or ATCOPIA78 insertions in the epiRILs or other experimental settings, or in nature. b Genome browser view of RNA-seq coverage of three genes hit by ATCOPIA93 in epiRIL394. c. Nectar secretion in flowers of epiRIL394 at F9 and F17. A nectar droplet is only observed at F17 (circle). d Structure of the FLC locus with the position of the ATCOPIA78 insertion in accession Ag-0 (top). Relative expression level of FLC at 10 and 60 days after germination (DAG) in plants containing (red) or lacking (blue) the ATCOPIA78 insertion and grown under control conditions (ctl.) or subjected to heat stress (HS) at the seedling stage (bottom). Data are mean ± s.d. (n > 9 independent samples, one biological experiment) and statistical significance for differences was obtained using the MWU test. e. Flowering time (mean ± s.d.; n > 9 independent samples, two independent experiments) for the same plants as in d. f Monthly mean temperature at collection sites for Ag-0 and 25 accessions sharing the same FLC haplotype but lacking the ATCOPIA78 insertion. Source data of Figure panels d and e are provided as a Source Data file