Unraveling Genetic Mysteries: Unlocking the Potential of Duplicate Genes through Regulation

Frederic Chain looking at fish.

Asst. Prof. Frederic Chain looking at stickles.

By Brooke Coupal

Genetic mutations are essential for human evolution, but they can also cause harm. 

Humans have about 20,000 genes in their genome (the entire set of DNA instructions found in a cell), and most of them have been created through genetic mutations that produce duplicate genes. Gene duplication allows organisms to evolve new biological functions, such as the ability to better digest starchy foods. However, having extra copies of genes can also cause imbalances associated with a wide range of health conditions, including cancer, cardiovascular disease and neurodevelopment disorders. 

Biological Sciences Asst. Prof. Frédéric Chain is researching a gene-regulation mechanism that could prevent such imbalances and help new genes evolve new functions. 

His work is being funded by a five-year, $1.35 million CAREER award from the National Science Foundation (NSF). The highly competitive grant is awarded to early-career faculty who, according to the NSF, “have the potential to serve as academic role models in research and education, and to lead advances in the mission of their department.”

Why is the regulation of duplicate genes important? 

FC: Every so often, cells in our body make mistakes that lead to DNA mutations that can be inherited. Some of these mutations generate duplicate copies of large segments of DNA that include entire genes. While gene duplication is a vital evolutionary process, genes are usually not a good thing to have duplicated in the short term, because they can cause genetic disorders and diseases. For this reason, most new duplicate genes will be eliminated over time by natural selection, preventing them from evolving new functions. 

I’m interested in how a cell regulates these extra copies to repress their potentially negative effects, allowing for the retention and evolution of duplicate genes. Understanding how the cell’s regulatory machinery handles newly duplicated genes is important in determining the initial processes by which new biological functions emerge in different organisms. The research can also provide insights into developing therapeutic targets for dealing with conditions associated with gene duplication.

What gene regulation mechanism are you studying? 

FC: I’m studying a mechanism in cells called epigenetic modification, where extra proteins and molecules can attach to DNA, affecting DNA shape and the way that genes work. We do not know the evolutionary impact of epigenetic modifications on newly emerged genes. I’m looking at whether this could allow duplicate genes to survive long enough in the genome and develop new functions. We will be using recent technological advances in gene sequencing, including long-read sequencing and epigenomic profiling, to test this hypothesis. 

You’re using stickleback fish to study gene regulation. Why these species? 

FC: Stickleback fish have been studied for over 100 years, mainly for their behavior and ecology, so we know a lot about different populations. They have become an important model organism to study evolution, thanks to having a diversity of population “ecotypes” that have adapted to distinct environments with a broad assortment of traits. Ten thousand years ago, before the last glaciation, stickleback fish mostly survived in marine environments. As those glaciers receded, they created lakes, streams, ponds and other freshwater environments. These fish were able to rapidly adapt to these environments, and new genes might have enabled this. So, they allow us to look at genetic and epigenetic changes that have arisen in different stickleback populations within the last few decades or centuries, and to evaluate how genes of different ages are regulated. 

Are there collaborators with this research project? 

FC: I’m getting support from my Department of Biological Sciences colleagues. Asst. Prof. Natalie Steinel has a stickleback fish lab and helps me with the field and lab work involving those organisms. Asst. Prof. Teresa Lee is an expert in epigenetics, so she can help with the interpretation of epigenetic data. Assoc. Prof. Jessica Garb is an expert in genomics, and she can also assist with data processing. I have external collaborators as well, including Assoc. Prof. Anne Dalziel at Saint Mary’s University, Prof. Catherine Peichel at the University of Bern, Asst. Prof. Trevor Krabbenhoft at the University at Buffalo and Dr. Philine Feulner, group leader of Fish Genomics at the Swiss Federal Institute of Aquatic Science and Technology. 

The diverse range of expertise that my collaborators bring will ensure the success of this research project and offer research opportunities to students in our labs. I have several students, from Ph.D. candidates to a first-year student, assisting me with the research. My goal is to train the next generation to lead the charge in genomics and bioinformatics research. 

Criteria for the NSF CAREER award include community service and a commitment to STEM diversity. How does your project meet these requirements? 

FC: Our research team will use data generated from this study to produce bioinformatics tutorials and run workshops for high school educators to develop genomics curricula to strengthen students’ coding and analytical skills. I’m collaborating with Sheila Kirschbaum, director of the Tsongas Industrial History Center (a partnership between UMass Lowell’s School of Education and the Lowell National Historical Park), to recruit high school teachers from the area. In the summer, we will take on local high school interns who will learn about biological data analysis and participate in our research. Being in Lowell is great because we can access students from underrepresented backgrounds in STEM and hopefully attract them to the field of bioinformatics.