Living organisms share an ancestor called the last universal common ancestor, or LUCA. LUCA is estimated to have lived approximately four billion years ago. All plants, animals, and microbes can trace their genealogy back to that original ancestral cell.
Since the 1980s, researchers have worked to determine the biological composition of LUCA by comparing the genomes of present-day organisms to identify similarities. These studies show that LUCA had a lipid membrane surrounding it, an active genetic code, and cellular machinery that allowed it to make proteins. In short, LUCA was not simply a mixture of chemicals. LUCA was a cell consisting of many components.
These results bring up the question of how LUCA came to contain all these biological components.
Researchers at Oberlin College (Oberlin, OH), Massachusetts Institute of Technology (Cambridge, MA), and University of Wisconsin-Madison (Madison, WI) feel they have found a method by which they can look back even further than LUCA. In the journal Cell Genomics, researchers Aaron Goldman from Oberlin, Greg Fournier from MIT, and Betül Kacar from Wisconsin describe the relationship between specific gene families and the events that occurred prior to the existence of LUCA.
“LUCA may be the most ancient organism that has been studied by evolutionary methodologies,” Goldman stated, “however, the genome of LUCA contained several genes that were present at the time of LUCA and had been preserved over time through unrestricted hybridization events.”
The researchers utilized a special type of gene called “universal paralogs.” To comprehend the concept of a paralog, it is important to first understand how a paralog is defined.
Paralogs arise as the result of gene duplication within a genome. Copies of the same gene might diverge in function and, therefore, represent different jobs for the gene. For instance, the gene for hemoglobin in humans exists in multiple forms. At some point in the past, one left its mark on human DNA as it duplicated and became specialized.
Gene duplication is an occurrence that is seen frequently. Approximately seventy percent of the protein-coding genes that exist in humans exist within gene families that each have at least one similar gene. Bacteria and Archaea carry many duplicated genes as well.
On the other hand, universal paralogs are different. Universal paralogs exist in every organism that is alive on the planet. These genes are made up of only a few gene families. The existence of these duplications in every organism today suggests they occurred before LUCA, and the genes were passed on from LUCA to all subsequent organisms.
Because these duplicates existed prior to LUCA, they provide scientists with information about a time prior to LUCA. Therefore, the few existing universal paralogs give scientists and the general public a rare opportunity to gain insight into the development of life prior to LUCA.
Goldman stated, “There are probably not very many universal paralogs. However, they can provide us insight into what life was like prior to LUCA.”
Over the past two and one-half decades, researchers have determined what LUCA likely looked like using phylogenetic methods. Using conserved genes, they concluded that LUCA likely possessed a membrane that regulated what could enter or exit the cell. Proteins that were used in the production and utilization of energy provide supportive evidence for this conclusion.
LUCA likely also contained a DNA genome. This genome would have encoded proteins for transcription of RNA and several types of proteins necessary for the repair of damaged DNA. While much is known about LUCA, there is some degree of uncertainty because there are no known universal DNA-replicating polymerases. LUCA has been suggested by some researchers to have a partially RNA-based life cycle.
It is likely that LUCA had a fully functional apparatus for copying, or translating, RNA into protein since it contained ribosomes constructed along the lines of the same general design as we see today. The molecular copy of the genetic code appeared to have come from LUCA and appears to have proteins that are fundamental to interpreting and constructing protein. LUCA also appeared to produce energy through ATP synthase by using the proton gradient to produce ATP.
LUCA had a very advanced molecular apparatus for creating living cells. These components were in place long before LUCA evolved as we know it today. This is where universal paralogs come into play.
“The only way we will have a history of these Early Lineages of single-celled organisms is through the study of Universal Paralogs,” states Fournier. Therefore, we need to extract all of the knowledge we can from universal paralogs.
The three authors of this paper summarized information about universal paralogs currently known and sorted these into two categories. The first group is involved in assembling proteins, and the second group is responsible for transporting proteins across cell membranes. Goldman’s laboratory at Oberlin examined one universal paralog family involved in embedding proteins, including enzymes, into membranes of cells.
He used evolutionary and computer-based tools to reconstruct the ancestral gene that existed before the duplication. The reconstructed protein was simpler than its basic descendant but was still able to interact with membrane proteins and bind to the protein-synthesizing machinery. It is likely that these early proteins assisted the first proteins in inserting into very simple membranes.
Recent studies have also examined the development of early parent forms of the enzyme responsible for attaching the amino acid to the tRNA. Data from these studies suggests that as these early enzymes came into evolution, they were much less selective than today’s enzymes in their binding to certain amino acids. Over a long time, as some of the genes were duplicated, their proteins were improved and specialized to perform their functions more effectively than when their function was first established.
Research on translation factors has produced evidence that it is likely that the common ancestor of all translation factors performed many functions in the process of creating proteins. As genes were duplicated, their posterior homologues evolved to perform more specific roles in the process of creating proteins.
According to Kaçar, “Following these universal paralogs allows us to build a bridge between the earliest events on planet Earth leading to the biological world and the research tools of today. It gives us a unique opportunity to directly study the history and evolution of our most profound and enigmatic knowledge of life.”
Using universal paralogs also enables researchers to establish the point at which they can pinpoint the root of the tree of life. Researchers have generally utilized an outgroup as a basis for determining the root of their evolutionary tree. However, when determining the evolutionary history of the entire tree of life, there is no single, clear outgroup.
Paired paralogs can serve as their own point of reference to centralize the analysis of the tree of life. The analysis of ATP synthase subunits and many other universal paralogs provides evidence for placing the tree of life’s root between the bacteria and the branches that lead to the archaea and eukaryote lineage.
Although advances in better algorithms and a broader range of data support this finding of universal paralogs, there are still limitations present. The intervening billions of years of gene losses and mutations have severely obfuscated any distinction of ancient biological signals. Therefore, when applying molecular techniques to understand ancient biological lifeforms, they cannot provide any insight into the period before genetic systems existed.
Through the utilization of universal paralogs, researchers can establish the time scale and develop an understanding of all cellular biological forms before LUCA, including previous biological forms.
Improvements in the accuracy of the biological model for reconstructing ancestral biological sequences, predicting protein structures, and utilizing artificial intelligence will eventually result in the discovery of new families of universal paralogs. In addition, the continued development of more accurate models for the prediction of amino acid substitutions, as well as a greater sample size of all known biological species, will assist in building universal paralogs.
As computational capabilities evolve and improve, researchers will be able to run even greater levels of model accuracy on the proteins present in ancient biological life. Some of these reconstructed ancient proteins may serve as the basis of new types of biological catalysts used in biotechnology.
Knowledge of when LUCA first existed will reshape our understanding of the emergence of biological life. Further, knowledge of the evolutionarily earliest systems will help laboratory researchers design more accurate models for testing to determine how the first cells would have operated.
Reconstructed ancestral proteins may have practical benefits to science as well, particularly in the development of synthetic biology and industrial chemistry. Additionally, the simplistic nature of these reconstructions may provide an avenue for researchers to develop new products for use in extreme conditions.
Furthermore, the work of this group has clarified the foundational framework for the field of evolutionary biology and the deep branches of the tree of life. In this context, it has strong implications for all future biological research in microbiology, medicine, and biotechnology.
The most important implication of universal paralogs is that they allow researchers to extend their work beyond LUCA and into previously unreachable areas of biological history. With the advent of enhanced research tools and comprehensive data, it is likely that scientists will be able to develop a clearer picture of the earliest stages of cellular life on Earth.
Research findings are available online in the journal Cell Genomics.
The original story “Scientists discover how life began before Earth’s first universal ancestor” is published in The Brighter Side of News.
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