Pangenome-resolved polymorphic transposable elements reveal human regulatory evolution in action
Transposable elements are a major source of gene-regulatory functions. Yet this contribution is understood largely from ancient insertions already fixed in the genome: the successes, seen long after the fact. The polymorphic phase before fixation or loss remains poorly resolved because such alleles could be scored only as present or absent. We resolved segregating transposable-element alleles as…
Transposable elements play a significant role in gene regulation, but their contribution is mainly understood from ancient insertions that have become fixed in the genome. However, the polymorphic phase leading up to fixation or loss has been difficult to discern due to the limitations in scoring such alleles as merely present or absent.
To overcome this challenge, researchers resolved segregating transposable-element alleles by using 231 haplotype-resolved human pangenomes along with matched long-read multi-omics. These findings revealed that the origins of these elements extend beyond recent transposition events. Their regulatory consequences depend on factors such as methylation and transcript context, often being overlooked by gene-level analyses.
Importantly, these transposable elements provide mechanisms at trait-associated loci and can be either advantageous or detrimental to selection. Ultimately, regulatory innovation before fixation is not a one-way accumulation process, but rather a complex mixture of gain, remodeling, and loss.
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