Quantitative Analysis of Spatial Distributions of All tRNA Genes in Budding Yeast

In the budding yeast nucleus, transfer RNA (tRNA) genes are considered to localize in the vicinity of the nucleolus; however, the use of Hi-C and fluorescent repressor-operator system techniques has clearly indicated that the tRNA genes are distributed not only around the nucleolus but also at other nuclear locations. However, there are some discrepancies between Hi-C data analysis and the results indicated from fluorescence microscopy data. To fill these gaps, we systematically clarified the spatial arrangements of all tRNA genes in the budding yeast nucleus using the genome simulation model developed by us. The simulation results revealed that out of 275 tRNA genes, 58% were found to be spatially distributed around the centromeres, 16% were distributed around the ribosomal DNA regions, and the remaining 26% were distributed between the centromeres and ribosomal DNA regions. Furthermore, 1% of all tRNA genes were found to be spatially distributed around the nuclear envelope, 30% were distributed around the center of the nucleus, and the remaining 69% were distributed between the nuclear envelope and the center of the nucleus. The percentage distributions were highly similar to those of the 176 tRNA genes encoding tRNAs having an anticodon for the optimal codons. The simulation results also revealed that the spatial arrangements of tRNA genes were affected by linear genomic distance from the tethering elements such as the centromeres or telomeres; however, the distance was only one of the factors to determine spatial distribution. This study also investigates whether tRNA gene transcriptional levels depend on the arrangements in the budding yeast nucleus by integrating the genome simulation model with tRNA sequencing data. The results suggest that the transcriptional levels did not depend on the arrangements in the nucleus. By using the genome simulation model, we showed the possibility of quantitatively analyzing genome structures.