DOI Bioasymmetry


Research Director: Hirofumi Doi
(President, CEO, Celestar Lexico-Sciences, Inc.)
Research Term: 1995-2000


The Doi Bioasymmetry project focused on the asymmetric replication of DNA and its role in cell differentiation and tissue development.

Reseach Results

New "index of rareness":  Since the genome needs to be treated as a whole, the proteome (proteins coded by the genome) was analyzed while looking for the frequencies of oligopeptides. An asymmetrical usage among the oligopeptides was noticed, suggesting that some "rare" oligopeptides are responsible for specific functions of proteins. A new "index of rareness" of oligopeptides was introduced in the proteome of the archaeon Methanococcus jannaschii using its complete genome data. This index was then applied to Pfu DNA polymerase from another archaeon, Pyrococcus furiosus. The amino acid residues of the enzyme having a high score of rareness were identified to be responsible for DNA elongation activity.

Change in gene expression:  Cells of budding yeast, Saccharomyces cerevisiae , show a typical asymmetric cell division. One becomes a mother cell and the other a young daughter, resulting in aging of the mother cell via division cycles. The change of Gene expression during asymmetric division cycles was observed using a DNA-array system. Many genes were expressed in young cells instead of old mother cells; particularly, several genes were specifically expressed in young cells. The expressions of several other genes were preferred in old cells. The genomic data necessary to investigate aging arising from asymmetric cell divisions are continuing to be studied.

Transient induction of transcripts:  To study the breakdown of symmetry of spherical mammalian eggs using mice embryos, cDNA libraries were constructed at each cell-stage from the unfertilized egg to the blastocyst stage. Based on cDNA collections made from each stage from egg to blastocyst, 25,438 3-ESTs were derived, and represent 9,718 genes, half of them novel. Thus, a considerable fraction of mammalian genes is dedicated to embryonic expression. This study revealed profound changes in gene expression that include the transient induction of transcripts at each stage. These results raise the possibility that development is driven by the actyionb of a series of stage-specific expressed genes.

Three C3H type zinc-finger genes:  C. elegans embryos repeat asymmetrical cell divisions to make the worm body. A prior machinery including arrangement of cytoskeleton to cause the asymmetric divisions should be installed during oocyte maturation. To find genes related to the prior machinery, the RNA interference technique was used. Three C3H type zinc-finger genes were identified to play crucial roles not only during early embryogeneis but also in the arrangements of chromosome and cytoskeleton during oocyte maturation.


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