Author SummaryInsertions and deletions (indels) represent a significant source of evolutionary change. In this manuscript, the authors investigate the patterns of genome-wide rate variation for indels that occurred in the human lineage since its divergence from chimpanzee. Earlier work suggested that insertion and deletion rates are correlated, implying that some genomic factors might affect both types of mutations and thus their patterns of variation across the genome. However, sequences evolving under and without selection were considered together. The present study represents the first attempt to quantify the levels of variation in neutral indel rates in the framework of multiple regression analysis. The finding that insertion versus deletion rates correlate with different genomic features suggests that these two types of mutation are caused in part by distinct molecular mechanisms. This conclusion has direct implications for understanding human genetic diseases, since a large number of them are caused by indels, and contributes to the growing recognition of the importance of fine-scale rearrangement in shaping genome evolution.