Distributed across two continents and thousands of islands, the Asian tropics are among the most species-rich areas on Earth. The origins of this diversity, however, remain poorly understood. Here, we reveal and classify contributions of individual tropical Asian regions to their overall diversity by leveraging species-level phylogenomic data and new fossils from the most species-rich Asian palm lineage, the rattans and relatives (Arecaceae, Calamoideae). Radiators (Borneo) generate and distribute diversity, incubators (Indochina, New Guinea, and Sulawesi) produce diversity in isolation, corridors (Java, Maluku, Sumatra, and the Thai-Malay Peninsula) connect neighboring regions, and accumulators (Australia, India, Palawan, and the Philippines) acquire diversity generated elsewhere. These contrasting contributions can be explained by differences in region size and isolation, elucidating how the unique island-dominated geography of the Asian tropics drives their outstanding biodiversity.
The post-transcriptional modification of tRNAs plays a crucial role in tRNA structure and function. Pathogenic variants in tRNA-modification enzymes have been implicated in a wide range of human neurodevelopmental and neurological disorders. However, the molecular basis for many of these disorders remains unknown. Here, we describe a comprehensive cohort of 43 individuals from 31 unrelated families with bi-allelic variants in tRNA methyltransferase 1 (TRMT1). These individuals present with a neurodevelopmental disorder universally characterized by developmental delay and intellectual disability, accompanied by variable behavioral abnormalities, epilepsy, and facial dysmorphism. The identified variants include ultra-rare TRMT1 variants, comprising missense and predicted loss-of-function variants, which segregate with the observed clinical pathology. Our findings reveal that several variants lead to mis-splicing and a consequent loss of TRMT1 protein accumulation. Moreover, cells derived from individuals harboring TRMT1 variants exhibit a deficiency in tRNA modifications catalyzed by TRMT1. Molecular analysis reveals distinct regions of TRMT1 required for tRNA-modification activity and binding. Notably, depletion of Trmt1 protein in zebrafish is sufficient to induce developmental and behavioral phenotypes along with gene-expression changes associated with disrupted cell cycle, immune response, and neurodegenerative disorders. Altogether, these findings demonstrate that loss of TRMT1-catalyzed tRNA modifications leads to intellectual disability and provides insight into the molecular underpinnings of tRNA-modification deficiency caused by pathogenic TRMT1 variants.