New Look at the Last Universal Common Ancestor

Despite their incredible diversity, almost all lifeforms, from bacteria to blue whales, share the same genetic code. The origins and timing of this code have sparked heated scientific debate.

Sawsan Wehbi, a PhD student in the Genetics Graduate Interdisciplinary Program at the University of Arizona, found compelling evidence that the textbook explanation of the evolution of the universal genetic code needs to be revised.

This is a novel approach to an old problem. Wehbi is the first author of a study that was published in the journal PNAS and suggests that the order in which the building elements of the code, amino acids, were recruited differs from the “consensus” of genetic code evolution.

The genetic code is this amazing thing in which a string of DNA or RNA containing sequences of four nucleotides is translated into protein sequences using 20 different amino acids. It is a mind-bogglingly complicated process, and our code is surprisingly good. It is nearly optimal for a whole bunch of things, and it must have evolved in stages.”

Joanna Masel, Study Senior Author and Professor, The University of Arizona

The study found that while amino acids that bind to metals joined much sooner than previously believed, early life preferred smaller amino acid molecules over larger and more complicated ones that were added later. Lastly, the team found that the genetic code of today probably evolved from earlier codes that are now extinct.

The authors contend that the current hypothesis of the code’s evolution is faulty since it is based on deceptive lab tests rather than evolutionary data. For instance, the renowned 1952 Urey-Miller experiment, which sought to replicate the conditions on early Earth that most likely saw the emergence of life, forms a fundamental part of traditional perspectives on the evolution of the genetic code.

The experiment’s ramifications have been questioned, despite its value in showing that simple chemical reactions might produce life's basic blocks, including amino acids, from nonliving matter.

For instance, it produced no sulfur-containing amino acids, even though sulfur was a common element on early Earth. Sulfuric amino acids are, therefore, thought to have entered the code considerably later. However, the outcome is unsurprising, given that sulfur was left out of the experiment’s ingredients.

According to co-author Dante Lauretta, Regents Professor of Planetary Science and Cosmochemistry at the University of Arizona Lunar and Planetary Laboratory, early life’s sulfur-rich nature has implications for astrobiology, particularly in understanding the possible habitability and biosignatures of extraterrestrial environments.

On worlds like Mars, Enceladus, and Europa, where sulfur compounds are prevalent, this could inform our search for life by highlighting analogous biogeochemical cycles or microbial metabolisms. Such insights might refine what we look for in biosignatures, aiding the detection of lifeforms that thrive in sulfur-rich or analogous chemistries beyond Earth.”

Dante Lauretta, Study Co-Author and Regents Professor, Planetary Science and Cosmochemistry, Lunar and Planetary Laboratory, University of Arizona

The researchers employed a new approach to evaluate amino sequences across the tree of life, all the way back to the last universal common ancestor, or LUCA, a hypothetical population of organisms that lived roughly 4 billion years ago and represents the shared progenitor of all species on Earth today. Unlike prior research, which analyzed full-length protein sequences, Wehbi and her team concentrated on protein domains, which are shorter segments of amino acids.

If you think about the protein being a car, a domain is like a wheel. It is a part that can be used in many different cars, and wheels have been around much longer than cars.”

Sawsan Wehbi, PhD Student, Genetics Graduate Interdisciplinary Program, University of Arizona

To determine when a certain amino acid was most likely recruited into the genetic code, the researchers employed statistical data analysis methods to examine the enrichment of each individual amino acid in protein sequences stretching back to LUCA and beyond.

An amino acid that appears preferentially in ancient sequences was likely introduced early on. In contrast, LUCA’s sequences are deprived of amino acids that were recruited later yet were available by the timeless ancient protein sequences emerged.

The team discovered almost 400 families of sequences dating back to LUCA. More than 100 began even earlier and had already diversified before LUCA. Although these amino acids were late additions to the code, they were found to possess more aromatic ring structures, such as tryptophan and tyrosine.

Masel concluded, “This gives hints about other genetic codes that came before ours, and which have since disappeared in the abyss of geologic time. Early life seems to have liked rings.”