Evolutionary view of the mechanism for immune diversity and genome instability

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Published: 21 Nov 2012
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Dr Tasuku Honjo – Kyoto University Graduate School of Medicine, Japan

Dr Tasuku Honjo talks to ecancer at the IFOM-Kyoto University Joint Symposium in Milan about the evolution of the AID enzyme and his institute in Japan.

Tell us about your institute in Kyoto.

My institute in Kyoto, Kyoto University, is the second oldest university in Japan and it specialises in a huge variety of fields including humanities and medical sciences. I belong to the medical faculty and specialise in molecular immunology which probably you are familiar about vaccination, how we can cope against infectious diseases.

What were the take home messages from your lecture?

What I spoke today is about how vaccination is effective. The vaccination principle, you give the shot and then you are immune for the rest of your life to the same virus or bacteria. That means we need some memory in our body. I am studying how this memory accumulates in our body and the way I study is this memory is very recently acquired during the evolution of life. It happened very recently with a small evolution of a single enzyme and that utilised pre-existing our genome instability, that means evolution depends on change of DNA and that system is also employed for our  memory of bacteria and viruses. The enzyme is called activation-induced cytidine deaminase and we abbreviate it AID.

When in evolution did the enzyme occur?

The first organism we can identify is a lamprey eel. So it’s not exactly our relative; they have a slightly different architecture of their body. Because this enzyme is very important to generate our immune system the enzyme was kept but subsequently other enzymes also jumped in to our body to make a different system, namely we have a reporter system to recognise a huge variety of antigens and the enzyme which I mentioned, AID, reporter recognition, and introduces genetic alteration to give memory in our cells. Memory is contained in the bone marrow derived lymphocytes and the memory is on our DNA, that is the key. Therefore it remains for a lifetime.

What about the instability?

Instability usually is not a good idea, we want to keep our DNA stable, this is the idea. However, suppose if we do not change our DNA at all there would be no evolution. The origin of life just stays as it is so we don’t exist here. So slight changes are important but not too much. Therefore this enzyme, AID, is restricted to the lymphocytes which are derived from the bone marrow cells.

How do you benefit from the institute partnership?

This is just starting. We are trying to establish another permanent collaboration status between IFOM and Kyoto and this is the first trial of how we can interact, how we can benefit, by this kind of interaction. But personally I believe this kind of international collaboration, especially through young scientists, is very critical in our future science.

Do you think this helps accelerate the pace of progress?

Very much because always interaction with different backgrounds, different ideas, different experiences, when they interact there are some new ideas and new creations. This is the essence of the science.