Professor Yang Jianrong: '(My) presentation will showcase the intriguing aspects and biological relevance of the phenotypic mutations.'
[Editor’s Note: Professor Yang Jianrong, a researcher and professor at with Sun Yat-sen University in Guangzhou, China, is a confirmed speaker at the upcoming Ninth Annual Mutational Scanning Symposium, March 25-27, in Melbourne, Australia. Here, he discusses his motivation for participating in the symposium and details of his presentation.]
Why did you agree to speak at the symposium?
Since I've been working with deep mutational scanning (DMS) data for over a decade, I'm always eager to get connected with colleagues and learn about creative uses of DMS. An old friend of mine, Dr. Xiaoyan Jia from Guangzhou Women and Children’s Medical Center, told me about the symposium. After learning about it, I knew I had to participate. Last year, I joined the Atlas of Variant Effect Alliance as a member of the Data Coordination and Dissemination workstream, but missed the previous symposium. So, when our workstream lead, Dr. Alan Rubin, invited me to speak this year, I accepted without hesitation.
What is the topic of your presentation?
I’ll be presenting my recent research on using DMS data to study interactions between phenotypic mutations — specifically, mistranscriptions and mistranslations. These molecular errors are often regarded as stochastic noise in genetic information transmission and tend to be overlooked, but they can have big impacts on human health. For instance, mistranslation occurs roughly once every 2,000 codons, meaning greater than 20 percent of human proteins contain at least one mistranslation. It can be highly cytotoxic, contribute to neurodegenerative diseases through protein destabilization and aging.
While studying genome-wide mistranslation rates and mistranscription rates in several model organisms, we found an unexpected negative correlation between the two. After further investigation, we realized that DMS data containing double mutants provides key insights into the evolutionary genetic mechanism behind this phenomenon. Essentially, we found that pervasive negative epistasis between mutations—revealed through DMS—explains the negative correlation we observed.
What do you hope symposium participants will learn from your presentation?
I expect that most attendees are familiar with genetic mutations, but less with phenotypic mutations. This presentation will, therefore, showcase the intriguing aspects and biological relevance of the phenotypic mutations. It will also highlight how DMS elucidates epistasis. This understanding is crucial for evolutionary predictions in biomedical contexts, such as in studies of pathogens.
Are there any speakers you are looking forward to hearing from and why?
I’m looking forward to hearing from Dr. Maitreya Dunham, as we share research interests in experimental evolution using yeast. I’m also eager to meet other colleagues, like Dr. Alan Rubin and Dr. Alex Wagner, to discuss ongoing developments in our DCD workstream, as well as Dr. Irene Gallego Romero, to learn more about her latest research on human evolution. Besides these conversations, I’d like to hear from other speakers about specific applications of DMS data, especially novel ways it can help solve Variants of Unknown Significance in human Mendelian diseases.
