The uplift of the Tibet Plateau (TP) during the Miocene is crucial to understanding the evolution of Asian monsoon regimes and alpine biodiversity. However, the northern Tibet Plateau (NTP) remains poorly investigated. We use pollen records of montane conifers ( Tsuga , Podocarpus , Abies , and Picea ) as a new paleoaltimetry to construct two parallel midrange paleoelevation sequences in the NTP at 1332 ± 189 m and 433 ± 189 m, respectively, during the Middle Miocene [~15 million years ago (Ma)]. Both midranges increased rapidly to 3685 ± 87 m in the Late Miocene (~11 Ma) in the east, and to 3589 ± 62 m at ~7 Ma in the west. Our estimated rises in the east and west parts of the NTP during 15 to 7 Ma, together with data from other TP regions, indicate that during the Late Miocene the entire plateau may have reached a high elevation close to that of today, with consequent impacts on atmospheric precipitation and alpine biodiversity.
When and how the TP underwent uplift and deformation are still under heated debate. We present paleomagnetic evidence for the NB in the northeastern central TP to help decipher the potential plateau deformation mechanism. Magnetostratigraphy with zircon U‐Pb age of volcanic rock demonstrates that the NB basin deposited during 52.5–35.0 Ma. Paleomagnetic declinations indicate that the basin experienced counterclockwise rotation of 25.9 ± 7.2° during 52–46 Ma and clockwise rotation of 24.4 ± 9.7° during 41–35 Ma, which coexisted with the intrusion and explosion of volcanic rocks at 51–46 and 39–35 Ma. We proposed a stepwise compression and extrusion model to interpret the basin deposition, rotation, and volcanism by northward compression and eastward extrusion of the eastern Lhasa and Qiangtang Blocks (Proto‐TP) in relation to the Sichuan Basin as early response to the India‐Asia collision.
Allostery is fundamental to many biological processes. Due to the distant regulation nature, how allosteric mutations, modifications, and effector binding impact protein function is difficult to forecast. In protein engineering, remote mutations cannot be rationally designed without large-scale experimental screening. Allosteric drugs have raised much attention due to their high specificity and possibility of overcoming existing drug-resistant mutations. However, optimization of allosteric compounds remains challenging. Here, we developed a novel computational method KeyAlloSite to predict allosteric site and to identify key allosteric residues (allo-residues) based on the evolutionary coupling model. We found that protein allosteric sites are strongly coupled to orthosteric site compared to non-functional sites. We further inferred key allo-residues by pairwise comparing the difference of evolutionary coupling scores of each residue in the allosteric pocket with the functional site. Our predicted key allo-residues are in accordance with previous experimental studies for typical allosteric proteins like BCR-ABL1, Tar, and PDZ3, as well as key cancer mutations. We also showed that KeyAlloSite can be used to predict key allosteric residues distant from the catalytic site that are important for enzyme catalysis. Our study demonstrates that weak coevolutionary couplings contain important information of protein allosteric regulation function. KeyAlloSite can be applied in studying the evolution of protein allosteric regulation, designing and optimizing allosteric drugs, and performing functional protein design and enzyme engineering.
The tectonic evolution of the eastern Paleo‐Tethys in the Three‐Rivers headwater region remains uncertain, especially because of the lack of quality paleomagnetic data from the east Eastern Qiangtang Terrane (EQT). Here, we present an integrated paleomagnetic and zircon U‐Pb geochronologic study of the Gadikao Formation (Fm.) volcanic rocks in the EQT. This previously assumed Carboniferous or Permian rock unit is now zircon U‐Pb dated to ∼254–248 Ma. Our new high quality (29 sites and 257 samples) inferred primary paleomagnetic results yield a robust Permo‐Triassic boundary paleopole of 59.7°N and 228.2°E (A95 = 3.3°), with a paleolatitude of 10.0 ± 3.3°N for the study area. Integrated with other reliable Permo‐Triassic paleomagnetic data of the EQT and the Tarim Block and other lines of geologic evidence, we propose that the EQT drifted continuously northward during 300–200 Ma and the Paleo‐Tethys Ocean probably closed at ∼232–220 Ma around the Qamdo region, most likely at 230 Ma.