By Liu Bo and Paul B. Brown*
Albert Szent-Gyorgyi de Nagyrápolt (1893-1986) won a Nobel Prize in 1937 for his discovery of vitamin C. He was one of the more interesting scientists of the 20th century. In addition to his discovery of vitamin C, he also participated in the Hungarian resistance during World War II, and later in the war, Adolf Hitler personally signed a warrant for his arrest. He immigrated to the US from his native Hungary in 1947 and established the Institute for Muscle Research at the Marine Biological Laboratory in Woods Hole, MA. Szent-Gyorgyi was interested in how cells functioned and this interest led him in many directions; antioxidant vitamins, cellular energy producing cycles, muscle fiber contractions, cancer and the use of quantum mechanics in cellular biology.
Nutrition has been described as an old and complex science in these articles, suggesting similar research questions and approaches will continually be employed as we determine the nutritional needs of new and emerging aquaculture species. We use Dr. Szent-Gyorgyi’s quote to remind us that even the oldest, most stubbornly entrenched scientific disciplines, are continually moving forward and progressing. There are a lot of thinkers out there. In this article, we consider one of the areas where nutrition and genetics may merge in the future and the possible ramifications of this merger in aquacultural applications.
Epigenetics refers to a pattern of gene expression within a cell or an organism, but a pattern not influenced by DNA sequence alteration. That is, not a mutation as most people would describe a mutation. Epigenetics is, however, a milder form of mutation that may be as much as “100,000 times more likely” to occur than a classic change in DNA content (Frank Johannes, University of Groningen, Netherlands). At present, epigenetic mechanisms include DNA methylation, histone modification, and chromatin conformational changes. DNA methylation is the most widely investigated epigenetic mechanism and we will restrict our consideration of epigenetics here to methylated DNA.
Chemically, methyl groups (CH3) are about the simplest biochemical compounds in nature and their metabolism is referred to as one carbon metabolism (1-C). When this simple 1-C molecule is attached to DNA, it blocks expression of the gene. The binding of 1-C to DNA is not haphazard, it is specific to the chemicals that makeup DNA and specific to genes. At the heart of epigenetics lies the interaction between nutrition and genetics.
Figure 1 is a schematic diagram of 1-C metabolism, which begins with the essential amino acid methionine and relies on several vitamins [folic acid, B12, B6 (pyridoxine), riboflavin, and choline] as well as two other nonessential amino acids, cysteine and betaine. Research in mammals found that inadequate supplies of the essential nutrients involved in 1-C metabolism will alter DNA methylation patterns and resulting gene expression. While these studies have not been conducted in aquaculture species, it is reasonable to assume conservation of these metabolic interactions across all vertebrates.
Figure 2 is the beginning of an interactive biochemical map showing the interaction between nutrition and epigenetics. The center column depicts the information from above and follows through to the processes we want to maximize in aquaculture (growth, reproduction, health, etc.). The two columns on the right and left depict the complex interactions that are likely to occur as a result of the basic interaction of nutrition and epigenetics. Nutrition is complex. Genetics is complex. If we combine the two, we double the fun (at the very least).
What does this complex discussion have to do with aquaculture? As stated earlier, we strongly suspect this will be a primary line of research in aquaculture in the future. Currently, there are only anecdotal data indicating epigenetic regulation of gene expression in aquacultural scenarios.
In Part 2 of this series, we will consider the available evidence and early experiments in this area of research.
Dr. Paul Brown is Professor of Fisheries and Aquatic Sciences in the Department of Forestry and Natural Resources of Purdue University. Brown has served as Associate Editor for the Progressive Fish-Culturist and the Journal of the World Aquaculture Society, among many others.
Dr. Liu Bo, Visiting Scholar at Purdue University, is Associate Professor at the Chinese Academy of Fisheries Science, Freshwater Fisheries Research Center, Wuxi City, China.