Genomic evidence reveals a radiation of placental mammals uninterrupted by the KPg boundary

Significance We produced a genome-scale dataset from representatives of all placental mammal orders to infer diversification timing relative to the Cretaceous–Paleogene (KPg) boundary. Our sensitivity analyses show that divergence time estimates within placentals are considerably biased by the specific way in which a given dataset is processed. We examined the performance of various dating approaches using a comprehensive scheme of likelihood analyses and computational simulations, allowing us to identify the optimal molecular clock parameters, gene sets, and gene partitioning schemes for reliable dating. Based on the optimal methodology, we present a hypothesis of mammalian divergence timing that is more consistent with the fossil record than previous molecular clock reconstructions, suggesting that placental mammals underwent a continuous radiation across the KPg boundary. The timing of the diversification of placental mammals relative to the Cretaceous–Paleogene (KPg) boundary mass extinction remains highly controversial. In particular, there have been seemingly irreconcilable differences in the dating of the early placental radiation not only between fossil-based and molecular datasets but also among molecular datasets. To help resolve this discrepancy, we performed genome-scale analyses using 4,388 loci from 90 taxa, including representatives of all extant placental orders and transcriptome data from flying lemurs (Dermoptera) and pangolins (Pholidota). Depending on the gene partitioning scheme, molecular clock model, and genic deviation from molecular clock assumptions, extensive sensitivity analyses recovered widely varying diversification scenarios for placental mammals from a given gene set, ranging from a deep Cretaceous origin and diversification to a scenario spanning the KPg boundary, suggesting that the use of suboptimal molecular clock markers and methodologies is a major cause of controversies regarding placental diversification timing. We demonstrate that reconciliation between molecular and paleontological estimates of placental divergence times can be achieved using the appropriate clock model and gene partitioning scheme while accounting for the degree to which individual genes violate molecular clock assumptions. A birth-death-shift analysis suggests that placental mammals underwent a continuous radiation across the KPg boundary without apparent interruption by the mass extinction, paralleling a genus-level radiation of multituberculates and ecomorphological diversification of both multituberculates and therians. These findings suggest that the KPg catastrophe evidently played a limited role in placental diversification, which, instead, was likely a delayed response to the slightly earlier radiation of angiosperms.