Inversions play an important role in disease and evolution but are difficult to characterize because their breakpoints map to large repeats. We increased by sixfold the number (n = 1,069) of previously reported great ape inversions by using single-cell DNA template strand and long-read sequencing. We find that the X chromosome is most enriched (2.5-fold) for inversions, on the basis of its size and duplication content. There is an excess of differentially expressed primate genes near the breakpoints of large (>100 kilobases (kb)) inversions but not smaller events. We show that when great ape lineage-specific duplications emerge, they preferentially (approximately 75%) occur in an inverted orientation compared to that at their ancestral locus. We construct megabase-pair scale haplotypes for individual chromosomes and identify 23 genomic regions that have recurrently toggled between a direct and an inverted state over 15 million years. The direct orientation is most frequently the derived state for human polymorphisms that predispose to recurrent copy number variants associated with neurodevelopmental disease.

倒位在疾病和进化中发挥着重要作用，但很难表征，因为它们的断点映射到大量重复。通过使用单细胞 DNA 模板链和长读长测序，我们将之前报道的类人猿倒位的数量增加了六倍（ n = 1,069）。我们发现，根据 X 染色体的大小和重复内容，倒位最富集（2.5 倍）。在大的（>100 千碱基 (kb)）倒位的断点附近存在过量的差异表达灵长类基因，但在较小的事件中没有。我们发现，当类人猿谱系特异性重复出现时，与祖先位点相比，它们优先（约 75%）以倒置方向出现。我们为单个染色体构建了兆碱基对规模的单倍型，并鉴定了 23 个基因组区域，这些区域在 1500 万年来一直在正向状态和反向状态之间反复切换。直接定向是人类多态性最常见的衍生状态，易导致与神经发育疾病相关的反复拷贝数变异。