Down syndrome in humans is caused by trisomy of chromosome 21. DSCR4 (Down syndrome critical region 4) is a de novo-originated protein-coding gene present only in human chromosome 21 and its homologous chromosomes in apes. Despite being located in a medically critical genomic region and an abundance of evidence indicating its functionality, the roles of DSCR4 in human cells are unknown. We used a bioinformatic approach to infer the biological importance and cellular roles of this gene. Our analysis indicates that DSCR4 is likely involved in the regulation of interconnected biological pathways related to cell migration, coagulation and the immune system. We also showed that these predicted biological functions are consistent with tissue-specific expression of DSCR4 in migratory immune system leukocyte cells and neural crest cells (NCCs) that shape facial morphology in the human embryo. The immune system and NCCs are known to be affected in Down syndrome individuals, who suffer from DSCR4 misregulation, which further supports our findings. Providing evidence for the critical roles of DSCR4 in human cells, our findings establish the basis for further experimental investigations that will be necessary to confirm the roles of DSCR4 in the etiology of Down syndrome.
The class Branchiopoda (Crustacea) shows great diversity in morphology and lifestyle among its constituent higher-level taxa: Anostraca, Notostraca, Laevicaudata, Spinicaudata, Cyclestherida and Cladocera. The phylogenetic relationships among these taxa have long been controversial. We sequenced three orthologous nuclear genes that encode the catalytic subunit of DNA polymerase delta and the largest and second-largest subunits of RNA polymerase II in the expectation that the amino acid sequences encoded by these genes might be effective in clarifying branchiopod phylogeny and estimating the times of divergence of the major branchiopodan taxa. The results of phylogenetic analyses based on these amino acid sequences support the monophyly of Branchiopoda and provide strong molecular evidence in support of the following phylogenetic relationships: (Anostraca, (Notostraca, (Laevicaudata, (Spinicaudata, (Cyclestherida, Cladocera))))). Within Cladocera, comparison of the nucleotide sequences of these same genes shows Ctenopoda to be the sister group of Haplopoda + Anomopoda. Three statistical tests based on the present amino acid sequence data—the approximately unbiased test, Kishino–Hasegawa test and weighted Shimodaira–Hasegawa test—tend to refute most of the previous molecular phylogenetic studies on Branchiopoda, which have placed Notostraca differently than here; however, our results corroborate those of one recent phylogenomic study, thus confirming the effectiveness of these three genes to investigate relationships among branchiopod higher taxa. Divergence time estimates calibrated on the basis of fossil evidence suggest that the first divergence of extant branchiopods occurred about 534 Ma during the early Cambrian period and that diversification within the extant branchiopod lineages started in or after the late Permian.
Small ubiquitin-related modifier (SUMO) is a post-translational modification factor composed of about 100 amino acid residues. Most plant species express a family of SUMO isoforms. We found three novel homologs of rice (Oryza sativa L.) SUMO genes, OsSUMO4, OsSUMO5 and OsSUMO6, in addition to the known SUMO genes OsSUMO1–OsSUMO3. Phylogenetic tree analysis revealed that rice SUMO genes have diverged considerably during their evolution. All six of these SUMO genes complemented the phenotype of the SUMO-deficient pmt3Δ mutant of fission yeast. Among the amino acid sequences of rice SUMO proteins, consensus motifs (ΨKXE/D) of the SUMO acceptor site were found in OsSUMO3, OsSUMO4, OsSUMO5 and OsSUMO6. The heat shock protein HSF7 is known to be SUMOylated in Arabidopsis thaliana. SUMOylation using a bacterial expression system revealed that the rice HSF7 homolog was modified by the six rice SUMOs, and further suggested that OsSUMO1, OsSUMO3, OsSUMO4 and OsSUMO6 are involved in its multiple SUMOylation.
Albino mutants (white coat and red eyes) of tanuki (Nyctereutes procyonoides viverrinus) have been repeatedly found in the Central Alps area of Japan. We recently reported that an albino tanuki from Iida, a city in this area, lacks the third exon of the TYR gene encoding tyrosinase, which is essential for melanin synthesis. The absence of this exon was due to the chromosomal deletion of a complex structure. In the present study, we analyzed TYR of another albino tanuki that was found in Matsusaka, a city located outside the mountainous area. In this animal, the third exon was also lost, and the loss was due to a deletion in which the structure was identical to that of the Iida mutant. Our results indicate, in consideration of the complex structure of the deletion, that the two albino animals inherited a single deletion that arose in their common ancestor. Iida and Matsusaka are approximately 170 km apart. This is, to our knowledge, the first report of an albino mutant gene that is widely distributed in mammalian natural populations. As the origin of this mutation is not known, the distance covered by the mutant gene remains unclear. If we assume that the mutation occurred halfway between Iida and Matsusaka, we can predict the migration distance to be approximately 85 km; however, if the mutation occurred at any other place, a longer distance would be predicted. Natural selection against albino tanuki may be relaxed because of a recent increase in food resources and refuge in urban areas.
It is vital to measure the levels of genetic diversity and differentiation between populations in a species to understand the current genetic structure and evolution of the species. Here, MIG-seq (multiplexed inter-simple sequence repeat genotyping by sequencing) was employed to assess the genetic variation in two tropical leguminous tree species, Dalbergia cochinchinensis and D. nigrescens, in Cambodia and Thailand. Sequence data for 255–618 loci, each with an approximate length of 100 bp, were obtained, and the nucleotide diversity, Tajima’s D and FST were computed. The estimates calculated from the data obtained by MIG-seq were compared to those obtained by Sanger sequencing of nine nuclear coding genes in D. cochinchinensis in our previous study. The nucleotide diversity at the MIG-seq loci was slightly higher than that at silent sites in the coding loci, whereas the FST values at the MIG-seq loci were generally lower than those at the coding loci, although the differences were not significant. Moreover, nucleotide diversities within populations of the two species were similar to each other, at approximately 0.005. Three and four population clusters were genetically recognized in D. cochinchinensis and D. nigrescens, respectively. Although the populations were differentiated from each other, the levels of differentiation among them, as measured by FST, were higher in D. cochinchinensis than in D. nigrescens. This indicates higher levels of gene flow between the populations in the latter species. We recommend using MIG-seq for quick surveys of genetic variation because it is cost-effective and results in smaller variance in the estimates of population genetic parameters.