Keio University Human BiologyMicrobiome-Quantum
Research Center (Bio2Q)

Message to Young Readers
Students at the high school level are often highly
enthusiastic and express a strong desire to pursue aparticular field. But surprisingly, these are often thesame students who end up stagnating. There’s noneed to rush into deciding on a research focus sosoon. Your four years at university should be spent
exploring a variety of subjects for a well-roundededucation. During that time, you can cultivateinterests that develop naturally and try to find a
graduate program that aligns with those interests.
Thinking too much about what you want to do too
early on can narrow your perspective. Read a wide
range of books, watch different kinds of movies, andacquire a broad education. Cherish the process of
discovering what genuinely interests you, and thenpursue that path.

I would like you to cherish theprocess of acquiring broad
knowledge and discovering whattruly interests you.
What is Bio2Q?
Bio2Q is a world-class research center at Keio University. It aims
to use quantum computing and AI to analyze the interaction
between Human Biology and Microbiome, revealing uncharted
territories of the human body and developing new treatments for
intractable diseases.

Keio University Shinanomachi Campus
35 Shinanomachi, Shinjuku-ku, Tokyo
160-8582, Japan

Email: sc-wpi-staff@adst.keio.ac.jp
Web: www.bio2q.keio.ac.jp
Tel: 03-6709-8106 (Weekdays 8:30 AM - 5:00 PM)

Professor
Haruhiko Siomi
Bio2Q Administrative Director/Genome Dynamics Team PI

ISSUE 04

Bio2Q

Bio2Q Researchers
MAR. 2024

It is the first private university to be selected for the World PremierInternational Research Center Initiative (WPI) program promotedby the Ministry of Education, Culture, Sports, Science andTechnology (MEXT).

Please tell us about your lab's research.

Copy-and-Paste Type Transposon

Our lab's research focuses on the study of early embryos within
the field of developmental biology, with a specific emphasis ontransposons, also known as transposable elements or "jumpinggenes," in genomes. Within the genome, which refers to thecomplete set of chromosomes that we have, these are calledtransposons.

↓Reverse Transcription

When transposons insert themselves into essential genes, they
can become the cause of diseases. On the other hand, when
considering evolution over a long time scale, it is believed thattransposons have contributed to changes in genome structureand function by moving around and making many copies ofthemselves.

↑Transcription

3↓InsertDNA (Genome)

Transposon

CopiedTransposon

Cut-and-Paste Type Transposon

CutoutInsert2

DNA (Genome)

Transposon
3

DNA (genome)So, transposons are helpful in the process of a
fertilized egg developing into an embryo?

Example 02

41

For example, humans and chimpanzees are different species. If
we trace back the evolutionary path, there was a divergence atsome point, leading to species differentiation. Although humans
and chimpanzees use almost the same set of genes, they arecontrolled differently. The variation in gene usage contributes tothe differences between species. Transposons are thought tohave played a significant role in such species differentiation.

Gene B

RNA

With the mouse as a model animal, we have found thatsuppressing the expression of transposons, specifically thoseexpressed around the 2-cell stage of early embryos, leads todevelopmental abnormalities. This research provides evidence
that the expression of transposons is essential for normaldevelopment, which is a groundbreaking discovery.

Gene ANew DNA

1Transposon

MovedTransposon

Transposons (mobile genetic elements) are thought to be closelyrelated to evolution.
Gene BHow do transposons move?

Yes, in terms of of their positive aspects, transposons are essential
for embryonic development and are believed to be closely related
to evolution. Transposons can be expressed in response to stress.
For example, transposons can be activated when cells experiencestress, such as a sudden increase in external temperature,exposure to UV radiation, or infection by bacteria or viruses. Froman evolutionary perspective, stress represents a change in theenvironment. To adapt to a new environment and leave behind
individuals better suited for survival, different genome sequences
need to be created. If transposons are expressed and transposedin germ cells in response to stress, when the fertilized egg
develops into an individual, with a new transposon insertion(s),which may be better adapted to the new environment.

There are two main mechanisms of movement: copy-and-pasteand cut-and-paste. In the copy-and-paste mechanism, thetransposon's DNA is transcribed into RNA, and this RNA is thenreverse-transcribed to create a new DNA copy. This new DNA
copy is then inserted into another part of the genome through theaction of specific proteins, effectively increasing the number ofcopies in the genome. This mechanism is common in mammals,
where each transposition event increases the number of copies
by one, leading to genome enlargement.

Humans have experienced major pandemics on the order ofcenturies, such as the Spanish flu in the early 1900s, which
resulted in millions of deaths worldwide. However, individualshave diverse genome sequences, so even when exposed to thesame virus, some may succumb quickly, while others may recoverdespite experiencing high fever. The diversity in our genome
sequences ensures that some individuals will survive. One of themechanisms that is thought to contribute to this diversity from an
evolutionary standpoint is the transposition of transposons inresponse to stress.

The cut-and-paste mechanism involves the transposon cutting
itself out and then re-inserting itself into a different part of thegenome. Since it cuts itself out, the number of copies generally
does not increase. This mechanism is more common in plants.

What would you say is one of the more interesting
experiences you've had during your time in research?

Do transposons have a specific role?
As mentioned earlier, transposons are involved in genome
enlargement and are believed to create new mechanisms forcontrolling gene expression. In other words, they are a source ofgenetic innovation. In a sense, the differences between humans
and chimpanzees can be attributed to where transposons areinserted. For instance, if there is a transposon insertion between
genes A and B in humans but not in chimpanzees, it may cause
genes A and B to be expressed differently in humans andGene A

2chimpanzees. About half of the human genome consists oftransposons and their remnants. Until recently, transposon
research focused exclusively on diseases caused by transposition. However, if they were entirely harmful, there should havebeen mechanisms to eliminate them. The fact that they have notbeen eliminated suggests that transposons may play some
important role. In our lab, we are exploring the positive aspects oftransposons and studying what happens when transposons areinactive.

Example 01

In Example 01, genes A and B are untangled(open), allowing gene expression control factors(transcription factors or chromatin modification
factors) to access the DNA and enable
expression.
In Example 02, the structure of gene B changes
due to a transposon insertion, preventing gene
expression control factors from accessing theDNA, resulting in an inability to express the gene.

A significant moment was when we realized that transposons,which until then had been mainly considered as causes ofdiseases, were actually indispensable for normal development.
For researchers, there's no equivalent of hitting a home run infront of tens of thousands of cheering fans. Even with the mostgroundbreaking discoveries, there are typically no more than afew people present, who may remark how incredible it is. Major
discoveries tend to be quiet affairs.
* 2-cell stage embryo: The stage at which the fertilized egg undergoes division,
resulting in two cells.