Datasets for: Tandem repeat variation within and between species reveals signatures of selection in humans and chimpanzees

Tandem repeats (TRs) are highly mutable DNA elements that influence gene regulation, protein structure, and disease. Until recently, their repetitive nature has hindered accurate TR sequencing and genotyping, resulting in sparse comparative data across species. In addition, we lack a population-aware model for analyzing TR conservation, divergence, and mutational dynamics. Here, leveraging telomere-to-telomere primate genomes and long-read data from 46 humans and 23 chimpanzees, we constructed a catalog of homologous TR loci and developed a framework to jointly analyze TR variation within- and between-species. Across primates, TR diversity and conservation vary strongly with genomic context, with coding and 5’ UTR TRs exhibiting reduced polymorphism and exceptional length conservation, consistent with pervasive stabilizing selection. Yet, while TRs are depleted in coding sequence, they are enriched in 5’ UTRs despite evolutionary constraint, suggesting a functional importance that outweighs their mutational risks. Heterozygosity varies across motif lengths and is concordant with mutation rate estimates from both evolutionary divergence and trio-based de novo mutation data. Introducing an HKA-like approach to control for locus-specific mutation rates, we identified TRs with signatures of directional and balancing selection. These candidates are enriched in genes involved in nervous system development and synaptic function, highlighting TRs as potential contributors to neural evolution. Further, TR divergence correlates with expression divergence in specific contexts, implicating a subset of regulatory TRs as candidates for adaptive expression evolution. Finally, comparison with chimpanzee data reveals that trait-associated TRs display longer alleles and higher diversity in humans, consistent with lineage-specific runaway mutations and/or directional selection. Together, our results establish a comparative framework for TR evolution, revealing how mutational processes and selection jointly shape repeat variation, and supporting their role as both conserved functional elements and as drivers of evolutionary innovation.