No abstract

The Late Paleogene surface height and paleoenvironment for the core area of the Qinghai-Tibetan Plateau (QTP) remain critically unresolved. Here, we report the discovery of the youngest well-preserved fossil palm leaves from Tibet. They were recovered from the Late Paleogene (Chattian), ca. 25.5 ± 0.5 million years, paleolake sediments within the Lunpola Basin (32.033°N, 89.767°E), central QTP at a present elevation of 4655 m. The anatomy of palms renders them intrinsically susceptible to freezing, imposing upper bounds on their latitudinal and altitudinal distribution. Combined with model-determined paleoterrestrial lapse rates, this shows that a high plateau cannot have existed in the core of Tibet in the Paleogene. Instead, a deep paleovalley, whose floor was <2.3 km above mean sea level bounded by (>4 km) high mountain systems, formed a topographically highly varied landscape. This finding challenges prevailing views on tectonic processes, monsoon dynamics, and the evolution of Asian biodiversity.

Mutations in the SCN1A gene have been identified in epilepsy patients with widely variable phenotypes and modes of inheritance and in asymptomatic carriers. This raises challenges in evaluating the pathogenicity of SCN1A mutations. We systematically reviewed all SCN1A mutations and established a database containing information on functional alterations. In total, 1,257 mutations have been identified, of which 81.8% were not recurrent. There was a negative correlation between phenotype severity and missense mutation frequency. Further analyses suggested close relationships among genotype, functional alteration, and phenotype. Missense mutations located in different sodium channel regions were associated with distinct functional changes. Missense mutations in the pore region were characterized by the complete loss of function, similar to haploinsufficiency. Mutations with severe phenotypes were more frequently located in the pore region, suggesting that functional alterations are critical in evaluating pathogenicity and can be applied to patient management. A negative correlation was found between phenotype severity and familial incidence, and incomplete penetrance was associated with missense and splice site mutations, but not truncations or genomic rearrangements, suggesting clinical genetic counseling applications. Mosaic mutations with a load of 12.5-25.0% were potentially pathogenic with low penetrance, suggesting the need for future studies on less pathogenic genomic variations.