Can You Teach an Old Gene New Tricks?

By Grishma Gupta
BMSIS Young Scientist Program

Evolution explains how living things change over successive generations, giving rise to diversity. Across the evolutionary history of Earth, the formation, changes, and extinction of species have been observed. Even though evolution happens very slowly, we see evidence of its action in the shared traits among seemingly unrelated species at the macroscopic and the genetic level. LUCA (Last Universal Common Ancestor) is the most recent common ancestor of all life forms on Earth, and is hypothesized to have lived 3.5 to 3.8 billion years ago. LUCA is said to be a single-celled organism with ring-shaped DNA floating freely within the cell, just like a tiny modern bacteria. The phylogenetic tree shows how LUCA gave rise to two types of simple cells – bacteria and archaea. After that, generations and generations of evolution led to the variety of multicellular organisms we see today in nature.

Fossils provide useful structural details, but not much information can be obtained about the molecules at that time in Earth’s history. Fortunately, molecular biologists have amazing tools that allow them to recreate ancestral genes in the lab that will help yield more information about evolution. Even though we can’t go back in time to obtain samples of these ancestral genes, scientists can predict their sequences based on statistics and our understanding of how genes work.

One of the most popular model organisms is the bacteria E. coli. E. coli is widely studied because it grows quickly in the lab and it’s full genome sequence is known, making it easy to manipulate for experiments.

Betul Kacar and her colleagues performed an experiment where they inserted artificial ancestral genes into the genome of E. coli to examine how the genes resembling different evolutionary time periods adapt to each other. The artificial genes used in this experiment were designed to imitate genes of a 700 million year old member of the phylum Proteobacteria.  

The experiment involved two genes named tufA and tufB. The letters “tuf” stand for “translation unstable factor.” These two genes are capable of producing an abundant and common bacterial protein named EFTu, which stands for “Elongation factor thermo unstable”. The EFTu protein actually stabilizes other proteins during a process critical to cell survival called translation. Translation is the way our genes are expressed as traits. Our body translates parts of the genetic code into instructions for making an enormous variety of proteins that our cells need to function.

The researchers first made artificial tufB and tufA genes in the lab, resembling what might have been in the ancient cell’s DNA. This is relatively easy to do because it is just a strand of DNA of the right sequence.  But, when the artificially-made ancestral tufB gene was inserted into the modern E. coli, fewer bacteria survived. This is because less of the necessary EFTu protein was produced. Why did this happen?

Let us simply this explanation by imagining that the E. coli cell is a company, and TufB is a energetic employee that is skilled at making the company’s main product, EFTu proteins. If TufB is replaced by a slower worker, then fewer EFTu proteins will be made and the company will not make as much profit. In other words, the laboratory-made “ancient” tufB gene is less capable of making EFTu than the modern tufB gene. As a result, the E. coli is less fit to survive. When that is the case, we say it has decreased fitness.

This experiment gave rise to ancient-modern hybrid E. coli cells with a decreased fitness level. After growing the microorganism for several generations, they underwent certain mutations that eventually fixed the harm caused by the replacement of the modern gene with the ancestral one. In a sense, it evolved before our very eyes!

The ability of an ancient gene to interact with all the components necessary for translation in modern E. coli indicate that coevolution of genes can occur. The results obtained from the study are of great importance in understanding the genetic mechanisms that contribute to the evolution of E. coli and may help us better understand the origin of life on Earth.

Research conducted at NASA Astrobiology Institute, Organismic and Evolutionary Biology, Harvard University, Department of Cell and Molecular Biology, Uppsala University, School of Biology, Georgia Institute of Technology, Petit H. Parker Institute for Bioengineering and Bioscience, Georgia Institute of Technology

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