Credit: Pixabay/CC0 public domainThe Human Genome Project had set a lofty goal to map the entire human genome. It seemed that the world was moving into personalized medicine. Evidence from our genetic material would help us in our treatment decisions.It was 2003. Nearly a decade later, we still wait for that promise. Although we may be able to identify a person's breast cancer gene, it is not certain if that person will develop the disease.Rama Singh, an evolutionary biologist at McMaster University, has found that there is another layer that regulates how genes interact and the billions of combinations that can produce certain results. This layer is made up of unexplored biochemical pathways that regulate gene expression through chemical reactions.Singh states, "Once we understood the genes, we thought we knew everything we needed to know." Singh says that individual genes are not the only way to find out the full story. It is how they interact that matters. The impact of single genes on the final expression of traits is usually very small."We must learn more about the combinations that unlock diseases, also known as'missing heritability'. Without knowing the pathways, knowing the genes is like knowing all the stoplights without seeing the layout of the streets.Singh said that coding genes to create identifiable outcomes like brown eyes, receding hair, or high cholesterol can be a difficult mathematical and scientific challenge. However, understanding the pathways that regulate genes activity can greatly simplify the challenge and help unlock the potential that was first discovered by the Human Genome Project."Isolating genes from the chromosome will not explain why there is no disease." Singh says that there is something in the biochemical pathways that we don't yet know how to measure. "We know that environmental and genetic variations have an impact on physical outcomes. But there is another component to this equation: pathway variation. A pathway-based approach is much more than just counting individual genes.Singh explains that there are a staggering number of gene combinations. This includes all genes in the human genome, including previous versions embedded in each cell's genetic history. Singh explains that an organism doesn't actively use all of its genetic material, but cells have backup copies of their own evolution to tap into when conditions change. This concept Singh calls "unnecessary complexity".Singh says that every organism has the ability to access past adaptations, which gives it the ability to adapt to its environment. Biochemical pathways allow cells to draw on this memory whenever necessary.It's similar to having both a savings and checking account. Singh says that while we use our checking account for daily expenses, we also have a savings account which can be accessed if necessary. Singh says that organizations have redundant genetic material they can draw on to help them survive in changing environments.Singh's new research was published in The Journal of Molecular Evolution. It is part of his ongoing efforts to integrate evolutionary biology with medical practice, an area of science he believes holds great promise.Singh dedicates the new paper in his memory to Richard Lewontin (an influential Harvard biologist who passed away July 4th). Singh had previously shared an earlier version of the paper.Rama S. Singh, Decoding Unnecessary Complexity: A Law of Complexity, and a Concept of Hidden Variation behind "MissingHeritability" in Precision Medicine. Journal of Molecular Evolution (2021). Rama S. Singh. Decoding "Unnecessary Complexity". A Law of Complexity, and a Concept Of Hidden Variation behind "Missing Heritability". Precision Medicine (2021). DOI: 10.1007/s00239-021-10023-3
