2022/07/06
In Part 1, we introduced the latest research of Professor Haruhiko Siomi and his colleagues, who have shown for the first time that eggs do not develop normally in golden hamsters that lack PIWI genes, which suppress transposon expression.
Part 2 begins with Prof. Siomi sharing the story of how transposons hold the key to maintaining species diversity.
Read Part 1 Here
While proliferated transposon expression may be associated with infertility, complete suppression of transposon activity during germ cell formation would prevent the creation of new mutations and halt biological evolution.
To preserve the potential for evolution, we also need a mechanism that produces new mutations at a particular frequency.
“According to Darwin's theory of evolution, an organism evolves through new mutations and their natural selection, and the lack of mutation would lead to no selection and, therefore, no survival. This is why I think our bodies are able to express transposons to some extent during the germ cell formation process and allow new mutations.”
Time and again, humans have been exposed to pandemics of infectious diseases such as COVID-19, but there are always survivors. This is precisely because of genome-level diversity, where infection-resistant genes are conserved at a certain frequency, even after an epidemic.
“That triggers the start of a new generation, and history repeats itself. In other words, transposons are the source of the mutations that we have within us. If we were to suppress them completely, that would mean zero mutations, and we would neither be able to evolve nor survive.
Genomic mutations are often single nucleotide units, but with transposons, large gene fragments can be jostled into place, creating massive changes. When newly transposed elements happen to be used as regulatory sequences, significant changes in gene expression can be expected. Of course, we cannot know whether all mutations will be good for us, but there will always be some among them that will allow us to cope with things like climate change, for example.”
The first of these reprogrammings occurs in early embryos. The genome is stripped of modifications once around the time that the fertilized egg divides into two, four, and eight cells.
“From there, when the genome is 'cleared' and development begins, structural changes in the genome and modifications specific to that stage are promoted, which is how our bodies are ultimately formed. That is the first time, and the other reprogramming happens at the very beginning of germ cell formation when the genome is once again stripped bare. From there, DNA methylation and different histone modifications are gradually added in the process of forming sperm and eggs to create a structure specific to mature sperm and a chromatin structure specific to eggs.”
This is how our genome is twice laid bare. When this happens, transposons that have been suppressed by various mechanisms are strongly expressed.
“We call this a ‘transposon expression burst,’ which occurs twice during the mammalian life cycle. And until recently, people wondered why such a dangerous thing would happen. The thinking was that these transposon expression bursts could cause jumps to new locations, making a mess of the genome.”
To their surprise, however, researchers found that transposons didn’t jump very often following one of these bursts.
“When a burst takes place, transposons are expressed, but not much jumping occurs. As we tried to understand the mechanism that causes expression but not jumping, it became clear that, in the case of germ cells, this was due to the PIWI-piRNA pathway I mentioned earlier. However, this has yet to be explained in early embryos, which is what we are now working to understand.”
Prof. Siomi and his colleagues think they are getting close to an answer.
“In a few more years, we believe that we will be able to elucidate the mechanism that prevents transposons from jumping when they are expressed in bursts during the crucial early embryonic period.”
“In my case, I had majored in organic chemistry at a university I chose after failing to get into my first pick. Although I studied hard and went on to earn a master's degree, I realized that I wanted to do other kinds of research in the future. At the time, I heard about a new laboratory in my field of interest that was recruiting people for a graduate school at Kyoto University, so I went to see if I could join. I hadn't studied medicine when I was an undergrad, but fortunately, the professor took a liking to me, and I was able to pass the entrance exam. At the lab, under the guidance of leading researchers including Nobel laureate Dr. Honjo. I was able to absorb a great deal of knowledge while studying the genetics of cancer.”
Haruhiko Siomi
Prof. Haruhiko Siomi received his master's degree from the Gifu University Graduate School of Agriculture in 1984 before entering a doctoral program at the Kyoto University Graduate School of Medicine. He completed his doctorate in 1988 and became a researcher at the Institute for Virus Research, Kyoto University. In 1990, he went to the University of Pennsylvania to serve as an HHMI fellow before becoming a postdoctoral fellow and assistant research professor in the Department of Biochemistry and Biophysics at the university’s School of Medicine. Starting in 1999, he served as a professor at the University of Tokushima's Institute for Genome Research and Graduate School of Medicine before assuming his current position in 2008. Since 2021, he has also served as Vice-President of Research at the Keio University School of Medicine.