Development of an accurate classification system of proteins into structured and unstructured regions that uncovers novel structural domains: its application to human transcription factors

<p>Abstract</p> <p>Background</p> <p>In addition to structural domains, most eukaryotic proteins possess intrinsically disordered (ID) regions. Although ID regions often play important functional roles, their accurate identification is difficult. As human transcription factors (TFs) constitute a typical group of proteins with long ID regions, we regarded them as a model of all proteins and attempted to accurately classify TFs into structural domains and ID regions. Although an extremely high fraction of ID regions besides DNA binding and/or other domains was detected in human TFs in our previous investigation, 20% of the residues were left unassigned. In this report, we exploit the generally higher sequence divergence in ID regions than in structural regions to completely divide proteins into structural domains and ID regions.</p> <p>Results</p> <p>The new dichotomic system first identifies domains of known structures, followed by assignment of structural domains and ID regions with a combination of pre-existing tools and a newly developed program based on sequence divergence, taking un-aligned regions into consideration. The system was found to be highly accurate: its application to a set of proteins with experimentally verified ID regions had an error rate as low as 2%. Application of this system to human TFs (401 proteins) showed that 38% of the residues were in structural domains, while 62% were in ID regions. The preponderance of ID regions makes a sharp contrast to TFs of <it>Escherichia coli </it>(229 proteins), in which only 5% fell in ID regions. The method also revealed that 4.0% and 11.8% of the total length in human and <it>E. coli </it>TFs, respectively, are comprised of structural domains whose structures have not been determined.</p> <p>Conclusion</p> <p>The present system verifies that sequence divergence including information of unaligned regions is a good indicator of ID regions. The system for the first time estimates the complete fractioning of structured/un-structured regions in human TFs, also revealing structural domains without homology to known structures. These predicted novel structural domains are good targets of structural genomics. When applied to other proteins, the system is expected to uncover more novel structural domains.</p

Searches for New Milky Way Satellites from the First Two Years of Data of the Subaru/Hyper Suprime-Cam Survey: Discovery of Cetus~III

We present the results from a search for new Milky Way (MW) satellites from the first two years of data from the Hyper Suprime-Cam (HSC) Subaru Strategic Program (SSP) $\sim 300$~deg$^2$ and report the discovery of a highly compelling ultra-faint dwarf galaxy candidate in Cetus. This is the second ultra-faint dwarf we have discovered after Virgo~I reported in our previous paper. This satellite, Cetus~III, has been identified as a statistically significant (10.7$\sigma$) spatial overdensity of star-like objects, which are selected from a relevant isochrone filter designed for a metal-poor and old stellar population. This stellar system is located at a heliocentric distance of 251$^{+24}_{-11}$~kpc with a most likely absolute magnitude of $M_V = -2.4 \pm 0.6$~mag estimated from a Monte Carlo analysis. Cetus~III is extended with a half-light radius of $r_h = 90^{+42}_{-17}$~pc, suggesting that this is a faint dwarf satellite in the MW located beyond the detection limit of the Sloan Digital Sky Survey. Further spectroscopic studies are needed to assess the nature of this stellar system. We also revisit and update the parameters for Virgo~I finding $M_V = -0.33^{+0.75}_{-0.87}$~mag and $r_h = 47^{+19}_{-13}$~pc. Using simulations of $\Lambda$-dominated cold dark matter models, we predict that we should find one or two new MW satellites from $\sim 300$~deg$^2$ HSC-SSP data, in rough agreement with the discovery rate so far. The further survey and completion of HSC-SSP over $\sim 1,400$~deg$^2$ will provide robust insights into the missing satellites problem.Comment: 12 pages, 12 figures, accepted for publication in PASJ special issu

Genetic diversity and structure in the Sado captive population of the Japanese crested ibis.

The Japanese crested ibis Nipponia nippon is a critically threatened bird. We assessed genetic diversity and structure in the Sado captive population of the Japanese crested ibis based on 24 and 50 microsatellite markers developed respectively for the same and related species. Of a total of 74 loci, 19 showed polymorphisms in the five founder birds of the population, and therefore were useful for the analysis of genetic diversity and structure. Genetic diversity measures, A, ne, He, Hoand PIC, obtained by genotyping of the 138 descendants were similar to those of other species with population bottlenecks, and thus considerably low. The low level of genetic diversity resulting from such bottlenecks was consistent with the results of lower genetic diversity measures for the Sado captive relative to the Chinese population that is the source population for the Sado group as determined using previously reported data and heterozygosity excess by Hardy-Weinberg equilibrium tests. Further, individual clustering based on the allele-sharing distance and Bayesian model-based clustering revealed that the founder genomes were equally at population in total, and with various admixture patterns at individual levels inherited by the descendants. The clustering results, together with the result of inheritance of all alleles of the microsatellites from the founders to descendants, suggest that planned mating in captive-breeding programs for the population has succeeded in maintaining genetic diversity and minimizing kinship. In addition, the Bayesian model-based clustering assumed two different components of genomes in the Sado captive Japanese crested ibis, supporting a considerably low level of genetic diversity