An “Oracle” for Predicting Evolution of Gene Regulation; Researchers Create Mathematical Framework to Examine Genome and Detect Signatures of Natural Selection, Deciphering the Evolutionary Past and Future of Non-Coding DNA

Despite the sheer number of genes that each human cell contains, these so-called “coding” DNA sequences comprise just 1% of our entire genome. The remaining 99% is made up of “non-coding” DNA--which, unlike coding DNA, does not carry the instructions to build proteins. One vital function of this non-coding DNA, also called “regulatory” DNA, is to help turn genes on and off, controlling how much (if any) of a protein is made. Over time, as cells replicate their DNA to grow and divide, mutations often crop up in these non-coding regions--sometimes tweaking their function and changing the way they control gene expression. Many of these mutations are trivial, and some are even beneficial. Occasionally, though, they can be associated with increased risk of common diseases, such as type 2 diabetes, or more life-threatening ones, including cancer. To better understand the repercussions of such mutations, researchers have been hard at work on mathematical maps that allow them to look at an organism’s genome, predict which genes will be expressed, and determine how that expression will affect the organism’s observable traits. These maps, called fitness landscapes, were conceptualized roughly a century ago to understand how genetic makeup influences one common measure of organismal fitness in particular: reproductive success. Early fitness landscapes were very simple, often focusing on a limited number of mutations. Much richer data sets are now available, but researchers still require additional tools to characterize and visualize such complex data. This ability would not only facilitate a better understanding of how individual genes have evolved over time, but would also help to predict what sequence and expression changes might occur in the future.

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