Co-option of transposable elements (TEs) to become part of existing or new enhancers is an important mechanism for evolution of gene regulation. However, contributions of lineage-specific TE insertions to recent regulatory adaptations remain poorly understood. Gibbons present a suitable model to study these contributions as they have evolved a lineage-specific TE called LAVA (LINE-AluSz-VNTR-Alu_LIKE), which is still active in the gibbon genome. The LAVA retrotransposon is thought to have played a role in the emergence of the highly rearranged structure of the gibbon genome by disrupting transcription of cell cycle genes. In this study, we investigated whether LAVA may have also contributed to the evolution of gene regulation by adopting enhancer function. We characterized fixed and polymorphic LAVA insertions across multiple gibbons and found 96 LAVA elements overlapping enhancer chromatin states. Moreover, LAVA was enriched in multiple transcription factor binding motifs, was bound by an important transcription factor (PU.1), and was associated with higher levels of gene expression in cis. We found gibbon-specific signatures of purifying/positive selection at 27 LAVA insertions. Two of these insertions were fixed in the gibbon lineage and overlapped with enhancer chromatin states, representing putative co-opted LAVA enhancers. These putative enhancers were located within genes encoding SETD2 and RAD9A, two proteins that facilitate accurate repair of DNA double-strand breaks and prevent chromosomal rearrangement mutations. Co-option of LAVA in these genes may have influenced regulation of processes that preserve genome integrity. Our findings highlight the importance of considering lineage-specific TEs in studying evolution of gene regulatory elements.

共同选择转座因子（TEs）成为现有或新的增强子的一部分是基因调控进化的重要机制。然而，沿袭特定的TE插入对最近的法规适应的贡献仍然知之甚少。长臂猿提出了一个合适的模型来研究这些贡献，因为它们进化出了特定于谱系的TE，称为LAVA（LINE- Alu Sz-VNTR- Alu _LIKE），在长臂猿基因组中仍然活跃。认为LAVA逆转录转座子通过破坏细胞周期基因的转录在长臂猿基因组的高度重排结构的出现中起作用。在这项研究中，我们调查了LAVA是否也可能通过采用增强子功能来促进基因调控的进化。我们对跨多个长臂猿的固定和多态LAVA插入进行了表征，发现96个LAVA元素与增强染色质状态重叠。此外，LAVA富含多个转录因子结合基序，被重要的转录因子（PU.1）结合，并与顺式中较高的基因表达水平相关。我们在27个LAVA插入物中发现了长臂猿特有的纯化/阳性选择标记。这些插入中的两个固定在长臂猿谱系中，并与增强子的染色质状态重叠，代表推定的LAVA增强子。这些推定的增强子位于编码SETD2和RAD9A的基因内，这两种蛋白可促进DNA双链断裂的精确修复并防止染色体重排突变。这些基因中LAVA的共同选择可能影响了保持基因组完整性的过程的调控。我们的发现强调了在研究基因调控元件的进化过程中考虑谱系特异性TE的重要性。