Deep hot mantle upwelling is widely revealed around the Qiongdongnan Basin on the northwestern South China Sea margin. However, when and how it influenced the hyper-extended basin is unclear. To resolve these issues, a detailed analysis of the Cenozoic time-varying residual subsidence derived by subtracting the predicted subsidence from the backstripped subsidence was performed along a new seismic reflection line in the western Qiongdongnan Basin. For the first time, a method is proposed to calculate the time-varying strain rates constrained by the faults growth rates, on basis of which, the predicted basement subsidence is obtained with a basin- and lithosphere-scale coupled finite extension model, and the backstripped subsidence is accurately recovered with a modified technique of backstripping to eliminate the effects of later episodes of rifting on earlier sediment thickness. Results show no residual subsidence in 45–28.4 Ma. But after 28.4 Ma, negative residual subsidence occurred, reached and remained ca. −1000 m during 23–11.6 Ma, and reduced dramatically after 11.6 Ma. In the syn-rift period (45–23 Ma), the residual subsidence is ca. −1000 m, however in the post-rift period (23–0 Ma), it is positive of ca. 300 to 1300 m increasing southeastwards. These results suggest that the syn-rift subsidence deficit commenced at 28.4 Ma, while the post-rift excess subsidence occurred after 11.6 Ma. Combined with previous studies, it is inferred that the opposite residual subsidence in the syn- and post-rift periods with similar large wavelengths (>102 km) and km-scale amplitudes are the results of transient dynamic topography induced by deep mantle upwelling beneath the central QDNB, which started to influence the basin at ca. 28.4 Ma, continued into the Middle Miocene, and decayed at ca. 11.6 Ma. The initial mantle upwelling with significant dynamic uplift had precipitated considerable continental extension and faulting in the Late Oligocene (28.4–23 Ma). After ca. 11.6 Ma, strong mantle upwelling probably occurred beneath the Leizhou–Hainan area to form vast basaltic lava flow.
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