RepeatFiller newly identifies megabases of aligning repetitive sequences and improves annotations of conserved non-exonic elements

Abstract

Transposons and other repetitive sequences make up a large part of complex genomes. Repetitive sequences can be co-opted into a variety of functions and thus provide a source for evolutionary novelty. However, comprehensively detecting ancestral repeats that align between species is difficult since considering all repeat-overlapping seeds in alignment methods that rely on the seed-and-extend heuristic results in prohibitively high runtimes. Here, we show that ignoring repeat-overlapping alignment seeds when aligning entire genomes misses numerous alignments between repetitive elements. We present a tool -RepeatFiller -that improves genome alignments by incorporating previouslyundetected local alignments between repetitive sequences. By applying RepeatFiller to genome alignments between human and 20 other representative mammals, we uncover between 22 and 84 megabases of previously-undetected alignments that mostly overlap transposable elements. We further show that the increased alignment coverage improves the annotation of conserved non-exonic elements, both by discovering numerous novel transposon-derived elements that evolve under constraint and by removing thousands of elements that are not under constraint in placental mammals. In conclusion, RepeatFiller contributes to comprehensively aligning repetitive genomic regions, which facilitates studying transposon co-option and genome evolution.Source code: https://github.com/hillerlab/GenomeAlignmentTools

Convergent and lineage-specific genomic differences in limb regulatory elements in limbless reptile lineages

“…We used axtChain (Kent et al, 2003) (default parameters except -linearGap = loose) to build co-linear alignment chains. The chains were subsequently processed by RepeatFiller (Osipova et al, 2019) (default parameters) to incorporate previously-undetected alignments between repetitive sequences and by chainCleaner (Suarez et al, 2017) (default parameters) to improve alignment specificity. Chains were converted to alignment nets using a modified version of chainNet (Kent et al, 2003) that computes real scores of partial nets.…”

Prevalent Introgression Underlies Convergent Evolution in the Diversification ofPungitiusSticklebacks

“…The lav files were then converted into psl format and chain together axt alignment using UCSC Genome Browser tools lavToPsl and axtChain. Next, newly detected repeat-overlapping alignments were incorporated into pairwise alignment chains using RepeatFiller ( Osipova et al 2019 ). Highly sensitive local pairwise alignment for loci flanked by aligning blocks was obtained using patchChain.perl ( Hiller et al 2013 ; Sharma and Hiller 2017 ), and the accuracy of local pairwise alignments was improved using chainCleaner ( Suarez et al 2017 ).…”

High-quality haploid genomes corroborate 29 chromosomes and highly conserved synteny of genes inHyleshawkmoths (Lepidoptera: Sphingidae)

“…Genomes were aligned using LASTZ 1.04.03 [85] with parameters (K = 2400, L = 3000, Y = 9400, H = 2000 and the lastz default scoring matrix). Then, we used axtChain [30] (default parameters except linearGap=loose) to compute co-linear alignment chains, RepeatFiller [86] (default parameters) to capture previously missed alignments between repetitive regions and chainCleaner [87] (default parameters except minBrokenChainScore=75000 and -doPairs) to improve alignment specificity. H. vespertilio was used as reference and H. euphorbiae , B. mori and M. sexta as queries.…”

“…To compare contiguity between H. euphorbiae, H. Genomes were aligned using LASTZ 1.04.03 [85] with parameters (K = 2400, L = 3000, Y = 9400, H = 2000 and the lastz default scoring matrix). Then, we used axtChain [30] (default parameters except linearGap=loose) to compute co-linear alignment chains, RepeatFiller [86] (default parameters) to capture previously missed alignments between repetitive regions and chainCleaner [87] (default parameters mapped to the H. euphorbiae genome using BLAT [30,31]. The alignment together with the M. sexta (XM_037446381) BLAT sequence results from both Hyles genomes was used to produce a small phylogenetic tree using the online RaxML [88] BlackBox portal (https://raxml-ng.vital-it.ch/#/) to illustrate orthology and variability.…”