Cellular research: the past is the key to unlocking the present, and the present is
the key to understanding the past
Institute for Chemical and Life Sciences, Faculty of Science and Technology,
Tokyo Institute of Technology
Professor Kan Tanaka
Where we came from is a question we all have. Compared to the origin of the universe andthe origin of the earth, there are many things we do not know about the origin and early evolutionof life, even though these are our direct roots.

I have been working from the viewpoint that thekey to unlocking the mysteries of evolution may lie in the mechanisms of the cell as we know ittoday.
The minimum unit of life on earth is the cell. There are two types of cells: prokaryotic cells,such as bacteria that do not have a cell nucleus, and eukaryotic cells that contain cell organelles(organelles) such as the nucleus and mitochondria inside the cell, both of which carry out life
activities according to the central dogma centered on the DNA genome.

Various theories havebeen proposed regarding the origin and evolution of these cells, but the current prevailing theoryis that life originated on earth as prokaryotic cells, and eukaryotic cells evolved through their
symbiosis. However, it is still unclear how prokaryotic cells emerged from non-living matter andhow eukaryotic cells evolved from prokaryotic cells.

Knowing the origin of cells leads tounderstanding their basic functions and mechanisms. Conversely, a deeper understanding ofcurrent cellular mechanisms should allow us to infer cell evolution. However, our knowledge has
not yet reached that level, and solving this mystery is one of the most important challenges ofmodern biology.
Our approach to these mysteries has been to study primitive microorganisms. When we thinkof eukaryotic cells, we think of animal and plant cells. However, these cells are very complex, andit is advantageous to use simpler microorganisms to study their basic mechanisms.

Theadvantage of microbial research can be recognized from the fact that Dr. Ohsumi's discovery ofautophagy was established in yeast research, and the basics of biology, central dogma, wereestablished in bacterial and phage studies. From this perspective, we are conducting our studying
using the unicellular algae Cyanidioschyzon merolae. Among
eukaryotic cell organelles, mitochondria and chloroplasts
have their own DNA genome and are thought to bedescendants of bacteria that symbiotically coexisted within
the cell in prehistoric times. Since cellular symbiosis is an
event closely related to the origin of eukaryotic cells and thePrimitive model eukaryotic cell

Cyanidioschyzon

subsequent origin of plant cells, clarification of how thesesymbionts "live" in the present-day cells will surely provide

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clues to the origin and early evolution of eukaryotic cells.
A Cyanidioschyzon cell contains one mitochondrion and one chloroplast; each multiplies by
repeating a replication cycle consisting of DNA replication and division. Of course, there is alsoa cell cycle centered on the nucleus. Therefore, in a Cyanidioschyzon cell, the three independent
replication cycles are coordinated under a certain relationship and function as a single cell. The
cell cycle begins with nuclear DNA replication, but in the replication cycle of the Cyanidioschyzon
cell, mitochondrial and chloroplast DNA replication occurs before nuclear DNA replication. We
have investigated the molecular mechanism that determines the order of DNA replication in detailand discovered how nuclear DNA replication awaits organelle DNA replication.

Until organelle

DNA replication occurs, nuclear DNA is not replicated because the cyclin proteins necessary for
nuclear DNA replication are actively degraded. When organelle DNA replication occurs, a signal
molecule (MgProto) is released from the chloroplast into the cytoplasm, inhibiting cyclin
degradation and inducing nuclear DNA replication. Chloroplasts are derived from photosyntheticbacteria (cyanobacteria), which cannot grow in the dark.

When cells divide under suchconditions, the proportion of chloroplast-free cells gradually increases. This very simple trick
was probably created in the early evolution of chloroplasts to stabilize the symbiosis by waiting forthe cell cycle to progress in the dark.

And as a result, we could assume that plant cells evolved

not to proliferate in the dark.
As described above, studying the relationship between the nucleus and symbiosis-derived
organelles will lead to a better understanding of the basic mechanisms of the present eukaryotic
cell and provide various insights into the origin of the eukaryotic cell. Going back even further,
the origin of prokaryotic cells should have been the very origin of life, but imagining that process
is even more difficult than considering the origin of eukaryotic cells.

However, complex cells

such as today’s bacteria did not arise suddenly but, in fact, evolved step by step from simpler
systems. The key to unlocking this path may be found in today’s cells.

Related Research Results
Kan Tanaka and Mitsumasa Hanaoka (2013) Hypothesis and theory: The early days of plastid
retrograde signaling with respect to replication and transcription. Front. Plant Physiol. 3, 301.
Yuki Kobayashi, Sousuke Imamura, Mitsumasa Hanaoka and Kan Tanaka (2011) A tetrapyrroleregulated ubiquitin ligase controls algal nuclear DNA replication. Nature Cell Biol. 13, 483-487.
Yuki Kobayashi, Yu Kanesaki, Ayumi Tanaka, Haruko Kuroiwa, Tsuneyoshi Kuroiwa and KanTanaka (2009) Tetrapyrrole signal as a cell cycle coordinator from organelle to nuclear DNA
replication in plant cells. Proc. Natl. Acad. Sci. USA 106, 803-807.

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