Decoding Dialects Key to Understanding the Language of DNA

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One of the most striking discoveries of the past century is that the language of DNA, the cellular blueprint that sits in all cells, is shared across all living organisms. Just as letters of the English alphabet are arranged to create sentences, paragraphs and stories, the alphabet of DNA is combined to create genes, chromosomes and genomes. This alphabet is composed of four molecules known as ATCG. Different combinations of these molecules produce the diversity of life on earth in the same way that different combinations of sentences produced both “Hamlet” and “Winnie the Pooh”.

Even though English has become a universal language spoken across the globe, there are numerous regional dialects that vary to different degrees. Carbonated beverages are referred to as pop in the Midwest, soda on the East Coast and coke in the South, for instance. In much the same way, organisms have their own dialects: preferences to use certain words and phrases more frequently than others. Therefore, the DNA of a redwood tree would be translated very poorly by the cellular machinery of a chimpanzee.

Technological breakthroughs in the ability to sequence DNA over the last decade have given researchers the full genomes of thousands of organisms. Using a variety of computational tools, researchers have begun to quantitatively study the variation in particular DNA “words” and “phrases” across the genomes of different species. This has allowed them to generate and test hypotheses about how variation in DNA dialect actually affects individual organisms and how it can be used for medical purposes, such as the production of vaccines.

For example, in 2008 researchers created a synthetic virus that codes for the same disease-causing proteins as a natural strain, but did so using a dialect that the host cells found difficult to understand. As a result, the viruses, when injected into mice, were unable to reproduce themselves as quickly as a natural virus would have. This extra time allowed the mice to develop immunity to the synthetic strain. And because the synthetic strain was so similar to the natural strain, the mice developed immunity to both. Following this general blueprint may lead to safe vaccines for novel viruses in the future. However, it all rests on our ability to understand the small differences between DNA dialects so that we can exploit those differences.

Some genes, such as those that confer antibiotic resistance, can actually be transferred between different organisms and species. But, how organisms cope with dialect problems when sharing genetic information is still relatively unknown. Understanding the history of gene transfers and the mechanism that allows their successful transfer may allow researchers to predict the conditions under which antibiotic resistance will and will not spread. Antibiotic resistant bacterial infections kill 90,000 people annually in the U.S., according to the Centers for Disease Control and Prevention, and are on the rise globally. Researchers may one day be able to save countless lives by preventing future transfers of unwanted antibiotic resistant genes.

The ability of microorganisms to translate DNA is fundamental in modern biological research. Scientists purposefully transfer genes between microorganisms to produce therapeutic proteins or industrially relevant chemicals, such as insulin or biofuels, in large quantities. Rather than isolating proteins from human cells, it is much simpler and faster to let bacteria, such as E. coli, over­produce the protein of interest by giving it the necessary genes. Of course, we now know that genes taken from one organism and given to another are often translated slowly and poorly. Re­writing these genes in a way that bacteria can better understand is akin to taking a complicated piece of literature and simplifying the sentences so that they are more easily understood. This can increase the genes’ production rates, lower drug costs for consumers, and accelerate the pace of biological research.

Understanding how different DNA dialects originate, spread, and are translated within cells may help develop safe and effective vaccines, limit the spread of antibiotic resistant genes, and lead to cheaper drugs and chemicals. Much of this research is still in very early stages, and has been made possible only recently with decreasing costs of DNA sequencing. As these costs continue to decline, more species sequences will be available, giving us a larger library of genetic stories. These stories will help us understand the language of DNA, and the different dialects that make us all unique. Whether it’s molecular, spoken or written word, it’s not just what you say, but how you say it.

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