Research

As Dobzhansky (1900-1975)'s 'Nothing in biology makes sense except in the light of evolution.', all characteristics of living organisms have emerged through evolution. To fundamentally understand them, we must delve into evolutionary processes. The physiological functions of our bodies are traits acquired by our ancestors over 3.6 billion years, and 'diseases,' where these biological functions are disordered, can only be understood by exploring the evolutionary background in which they arise. Since Darwin published On the Origin of Species over 150 years ago, evolutionary biology has continued to develop. During this time, we have unraveled the mechanisms of heredity at the molecular level, and the ability to directly analyze DNA, the molecule that encodes genetic information, has transformed evolutionary biology. It has shifted from a field that debated theoretical models to one that investigates genetic changes involved in evolution. Now, by linking this to advanced pathology, we can gain an understanding of the 'origin of disease' and potentially revolutionize our foundational knowledge for medical science."

Genetic factors contribute not only to genetic diseases but also to susceptibility to all kinds of illnesses. These genetic factors are encoded in the 'genome DNA,' which can be thought as the blueprint of biological systems. When we observe the precision and beauty of biological functions, it may seem as designed, but upon examining the primary information—genome sequences, it becomes clear that they are, in fact, products of random, haphazard events.

We can see evolutionary process of our genome when compared to other individuals and species. The primary factor driving this evolution is mutation, which is far from orderly. Mutations arise from DNA replication errors, accidental damage, flawed repairs, mistaken copy-and-paste processes during DNA replication or recombination, and even selfish genetic elements selfishly replicating themselves within the genome. This chaotic process contrasts with the higher-order functions it produces. Along with mutations, other evolutionary processes like selection, gene flow, recombination, and genetic drift shape our genome, which results in biological systems.

We are often captivated by the beauty of life and tempted to view evolution as a form of refinement. However, the 'dissonance' of diseases in biological systems embodies this chaotic genome evolution, suggesting that the roots of illness lie within the real processes of our genome evolution. Much of the variability in disease susceptibility among people today is a result of human diversity built up through evolutionary processes. Looking more broadly, we see that certain diseases are shared with other animals, while others are unique to humans. Some illnesses may have roots tracing back to our unicellular ancestors, while others arose only with the emergence of humans. Certain species may have evolved similar diseases to ours, while others have overcome them. Examining this diversity across species can illuminate not only the origins of disease but also potential solutions.

By analyzing genome sequence diversity, we can explore both interspecies and intraspecies diversity, helping us to understand why diseases arise and persist. Recent advancements in genome sequencing technology allow us to analyze entire genomes at a low cost. Many genomes, including those of humans and primates, have already been sequenced and made publicly available. Our lab conducts fundamental 'genome diversity' research using model organisms to experimentally explore the causes of genomic diversity, and applied research comparing diverse genome sequences across and within species to reveal evolutionary patterns of pathogenic mutations and disease-related genes. By connecting evolutionary biology with pathology, we aim to better understand these processes.

To conduct the mission of the Brain Research Institute at Niigata University, our research focuses primarily on neurological disorders, as these are directly related to the ultimate challenge to human brain evolution. We anticipate exciting outcomes and, through collaboration with leading scientists and the unique resources of the institute’s neuropathology expertise, we aim to get experimental evidence and create a roadmap that could lead to medical advancements.

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