Prehistoric human migration between Sundaland and South Asia was driven by sea-level rise.

Rapid sea-level rise between the Last Glacial Maximum (LGM) and the mid-Holocene transformed the Southeast Asian coastal landscape, but the impact on human demography remains unclear. Here, we create a paleogeographic map, focusing on sea-level changes during the period spanning the LGM to the present-day and infer the human population history in Southeast and South Asia using 763 high-coverage whole-genome sequencing datasets from 59 ethnic groups. We show that sea-level rise, in particular meltwater pulses 1 A (MWP1A, ~14,500-14,000 years ago) and 1B (MWP1B, ~11,500-11,000 years ago), reduced land area by over 50% since the LGM, resulting in segregation of local human populations. Following periods of rapid sea-level rises, population pressure drove the migration of Malaysian Negritos into South Asia. Integrated paleogeographic and population genomic analysis demonstrates the earliest documented instance of forced human migration driven by sea-level rise.

Vertical stratification of the air microbiome in the lower troposphere.

The troposphere constitutes the final frontier of global ecosystem research due to technical challenges arising from its size, low biomass, and gaseous state. Using a vertical testing array comprising a meteorological tower and a research aircraft, we conducted synchronized measurements of meteorological parameters and airborne biomass (n = 480) in the vertical air column up to 3,500 m. The taxonomic analysis of metagenomic data revealed differing patterns of airborne microbial community composition with respect to time of day and height above ground. The temporal and spatial resolution of our study demonstrated that the diel cycle of airborne microorganisms is a ground-based phenomenon that is entirely absent at heights >1,000 m. In an integrated analysis combining meteorological and biological data, we demonstrate that atmospheric turbulence, identified by potential temperature and high-frequency three-component wind measurements, is the key driver of bioaerosol dynamics in the lower troposphere. Multivariate regression analysis shows that at least 50% of identified airborne microbial taxa (n = ∼10,000) are associated with either ground or height, allowing for an understanding of dispersal patterns of microbial taxa in the vertical air column. Due to the interconnectedness of atmospheric turbulence and temperature, the dynamics of microbial dispersal are likely to be impacted by rising global temperatures, thereby also affecting ecosystems on the planetary surface.

Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes.

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.

Whole-Genome Sequence of Bacillus megaterium Strain SGAir0080, Isolated from an Indoor Air Sample.

Bacillus megaterium strain SGAir0080 was isolated from a tropical air sample in Singapore. Its genome was assembled using single-molecule real-time (SMRT) sequencing and MiSeq reads. It has one chromosome of 5.06 Mbp and seven plasmids (average length, 62.8 kbp). It possesses 5,339 protein-coding genes, 130 tRNAs, and 35 rRNAs.

Complete Genome Sequence of Microbacterium sp. Strain SGAir0570, Isolated from Tropical Air Collected in Singapore.

Microbacterium sp. strain SGAir0570 was isolated from air samples collected in Singapore. Its genome was assembled using single-molecule real-time sequencing and MiSeq short reads. It has one chromosome with a length of 3.38 Mb and one 59.2-kb plasmid. It contains 3,170 protein-coding genes, 48 tRNAs, and 6 rRNAs.

Biophysical Aspect of Huntingtin Protein During polyQ: An In Silico Insight.

Huntington's disease (HD) is a neurodegenerative disorder that is caused by an abnormal elongation of the polyglutamine (polyQ) chain in the Huntington (Htt) protein. At present, the normal function of Htt of neurons as well as the mechanism by which selective neurodegeneration is caused by the expanded polyQ chain in Htt remains ambiguous. A gain of function as a result of the elongated polyQ chain can lead to abnormal interaction of the Htt protein with its interacting partners, thereby resulting in the neuropathological changes seen in the Huntington's disease. Recent research indicates protein kinase C and casein kinase substrate in neurons protein 1 (PACSIN1) as one of the interacting partners of Htt protein. It has proven experimentally that the mutant Htt and PACSIN1 formed aggregates in the cytoplasm. This aggregation is believed to be a cause for Huntington's disease. In our study, we performed in silico investigations to predict the biomolecular mechanism of Htt/PACSIN1 interaction that could be one of the major triggers of the disease. Biomolecular interaction and molecular dynamics simulation analysis were performed to understand the dynamic behavior of native and mutant structures at the atomic level. Mutant Htt showed more interaction with its biological partner than the native Htt due to its expansion of interaction surface and flexible nature of binding residues. Our investigation of native and mutant Htt clearly shows that the structural and functional consequences of the polyQ elongation cause HD. Because of the central role of the Htt-PACSIN1 complex in maintaining connections between neurons, these differences likely contribute to the mechanism responsible for HD progression.

Biophysical aspect of phosphatidylinositol 3-kinase and role of oncogenic mutants (E542K & E545K).

Genetic variations in oncogenes can often promote uncontrolled cell proliferation by altering the structure of the encoded protein, thereby altering its function. The PI3KCA oncogene that encodes for p110α, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is one the most frequently mutated oncogenes in humans. PI3K plays a pivotal role in cell division. PI3K consists of two subunits: the catalytic (p110α) and regulatory (p85α). The regulatory subunit usually controls the catalytic subunit and switches off the enzyme when not required. It is believed that mutations in PI3KCA gene can alter the control of p85α over p110α and can sustain p110α in a prolonged active state. This in turn results in uncontrolled cell division. In this study, we investigate the pathogenic role of two point mutations: E542K and E545K on p110α subunit and how they alter its binding with the regulatory subunit. Molecular interaction and molecular dynamic simulation analysis are performed to study the dynamic behaviour of native and mutant structures at atomic level. Mutant p110α showed less interaction with its regulatory partner p85α than the native did, due to its expanded and rigid structure. Our analysis clearly points out that the structural and functional consequences of the mutations could promote tumour proliferation.

Computational investigation of molecular mechanism and neuropathological implications in Huntington disease.

Huntington's disorder (HD), caused by mutations of the IT-15 gene, is an autosomal genetic disease that causes the breakdown of the nerve cells in the brain. The IT-15 gene encodes the huntingtin (Htt) protein. Htt, along with its interacting partners, are involved in maintaining proper communication among neurons. Our work is based on the interaction behavior between Htt (in three polyglutamine (polyQ) states that is Htt 0Q, 17Q and 36Q) and SH3GL3 interacting protein by using computational methods. We used the HADDOCK docking platform to find out the extent of interaction between Htt polyQ models and SH3GL3. The Htt36Q (mutated) showed higher interaction than Htt17Q (native) with SH3GL3. Molecular dynamics simulation was performed to uncover the structural fluctuations of polyQ models and their complexes. RMSD, Rg, SASA, and total interaction energy graph showed significant results, where as mutant Htt showed higher fluctuations and flexibility than native Htt. The increase in the length of polyQ was found to affect the stability, flexibility, and compactness of the protein and its complex. Our research provided a propitious approach to understand the consequence of polyglutamination in Htt and its relation with HD.