Co-option of the lineage-specificLAVAretrotransposon in the gibbon genome

Abstract

Transposable elements (TEs) can shape gene regulation networks by being co-opted as enhancers.However, the contribution of lineage-specific TE insertions to recent adaptations remains poorly understood. Gibbons present a suitable model to study these contributions, as they have evolved many distinct traits, including heavily rearranged genomes and a novel TE called LAVA. The LAVA retrotransposon is still active in the gibbon genome and is thought to have contributed to evolution of gibbon-specific traits. In this study, we characterized fixed and polymorphic LAVA insertions across multiple gibbon genomes and found that 10% of all LAVA elements overlap chromatin states associated with enhancer function. Moreover, LAVA was enriched in multiple transcription factor motifs, was bound by the important lymphoid transcription factor PU.1, and was associated with higher levels of gene expression in cis. Interestingly, despite the highly similar genomic distribution and epigenetic characteristics of fixed and polymorphic LAVA, only fixed LAVA insertions showed strong signatures of positive selection, and were enriched near genes implicated in DNA repair. Altogether, our population genetics, epigenetics, and evolutionary analyses indicate that several LAVA insertions have been coopted in the gibbon genome as cis-regulatory elements. Specifically, a subset of the fixed LAVA insertions appear to have been co-opted to enhance regulation of DNA repair genes, likely as an adaptive mechanism to improve genome integrity in response to the genomic rearrangements occurring in the gibbon lineage. evolution of gene-regulatory adaptations remains poorly understood, especially in non-human primates.Among primates, the endangered gibbons (Hylobatidae) present an attractive model for exploring functional contributions of a lineage-specific TE. Gibbons (or small apes) have an intriguing evolutionary history, and have evolved many unique traits [e.g. locomotion via brachiating, monogamy, etc. (9)]. Most notably, the gibbon lineage has experienced drastic genomic rearrangements since its divergence from the common Hominidae ancestor ~17 million years ago (mya) (10). These evolutionary rearrangements are not only evident through comparisons with great ape genomes, but also in the vastly different karyotypes of the four extant gibbon genera: Nomascus (2n=52), Hylobates (2n=44), Hoolock (2n=38) and Siamang (2n=50), which split only 5 mya. The factors leading to these evolutionary genome reorganizations are not fully understood, but a gibbon-specific retrotransposon, called LAVA (Fig. 1A), may have played a role (11).The LAVA element is a non-autonomous composite retrotransposon consisting of portions of repeats found in most primate genomes (CT-rich, Alu-like, a truncated SVA element, and portions of AluSz and L1ME5 elements), but the fully assembled element is only found among gibbons (12, 13). In the original analysis of the reference gibbon genome, which was derived from a northern white-cheeked gibbon (Nomascus leucogenys), nearly half of ...

Co-option of the lineage-specificLAVAretrotransposon in the gibbon genome

“…To investigate if LAVA elements have evolved regulatory function in the gibbon genome, we sought to identify LAVA elements displaying epigenetic hallmarks of enhancer activity. We performed chromatin immunoprecipitation sequencing (ChIP-seq) against three activating (H3K4me1, H3K27ac, and H3K4me3) and two repressing histone marks (H3K27me3 and H3K9me3), using Epstein-Barr Virus (EBV)-transformed lymphoblastoid cell lines (LCLs) established from three unrelated NLE individuals previously (12,30) and in this study (Dataset S4) (18). We annotated the epigenetic landscape of the gibbon genome using nine chromatin states, each of which represented a different combination of histone marks (Fig.…”

“…The LAVA VNTR is composed of variable numbers of 30-to 50-bp tandem repeat units, leading to most LAVA elements containing several closely spaced PU.1 binding motifs (12.8 ± 11; mean ± SD). To validate binding of PU.1 to LAVA, we performed ChIP-seq against PU.1 in two gibbon LCLs (Dataset S4) (18). We first used the RepEnrich2 software (34), which takes advantage of both unique and multimapping sequencing reads to assess overall enrichment of repeat families in ChIP-seq samples relative to input (indicating binding), without the need for high mappability or peak calling.…”

Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors

“…To study the evolution of the human hippocampus from a developmental standpoint, we investigated the extent to which TEs contributed to gene expression profiles of human and chimpanzee hippocampal intermediate progenitors. TEs account for nearly ∼50% of the human genome composition and many elegant studies have established that at least a fraction of the TEs can regulate the host genes in humans and other primates (Chuong et al, 2013; Chuong et al, 2016; Cosby et al, 2021; del Rosario et al, 2014; Du et al, 2016; Fuentes et al, 2018; Jacques et al, 2013; Judd et al, 2021; Lynch et al, 2011; Lynch et al, 2015; Mika et al, 2021; Modzelewski et al, 2021; Okhovat et al, 2020; Rayan et al, 2016; Schmidt et al, 2012; Sundaram et al, 2014; Trizzino et al, 2017; Trizzino et al, 2018; Ward et al, 2018; Xie et al, 2013).…”

Evolution and antiviral activity of a human protein of retroviral origin

“…These and additional syntenic SUPYN and SYN2 open reading frame sequences were validated/identified by BLASTn ( 70 ) search with default settings of publicly available Catarrhine primate genomes (ncbi.nih.gov). Mariam Okhovat of the Carbone Lab (Oregon Health and Science University) generously provided BAM files containing read alignment information for SUPYN, SYN1 , and SYN2 generated from whole genome sequencing of Hoolock leuconedys (Hoolock Gibbon), Symphalangus syndactylus (Siamang), Hylobates muelleri (Müller’s Gibbon), Hylobates lar (Lar Gibbon), Hylobates moloch (Silvery Gibbon), Hylobates pileatus (Pileated Gibbon), and Nomascus gabriellae (Yellow-cheeked Gibbon) ( 71 ). Where multiple individuals were sequenced, a consensus sequence was generated using samtools ( 59 ) and JalView ( 72 ).…”

“…Orthologous SUPYN, SYN1, and SYN2 sequences were extracted from the 30-species MULTIZ alignment (13) and formatted for sequence alignment using the phast package (69) Nomascus gabriellae (Yellow-cheeked Gibbon) (71). Where multiple individuals were sequenced, a consensus sequence was generated using samtools (59) and JalView (72).…”