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Unlocking Life’s Origins: Studying Genes Before the Last Universal Common Ancestor

by Lisa Park - Tech Editor

Scientists are gaining unprecedented insight into the earliest stages of life on Earth, peering back beyond the “last universal common ancestor” (LUCA) – the single-celled organism from which all known life descends. A new approach, detailed in research published this week, focuses on a unique class of genes called “universal paralogs” to reconstruct the characteristics of life before , when the findings were released.

For decades, the LUCA has represented a boundary in our understanding of life’s origins. While research on the LUCA has revealed that essential features like cell membranes and DNA were already established around four billion years ago, it left a significant gap in understanding how life initially took shape. The new research, led by Aaron Goldman of Oberlin College, Greg Fournier of MIT, and Betül Kaçar of the University of Wisconsin-Madison, bypasses this limitation by examining genetic material that predates the LUCA itself.

“Although the last universal common ancestor is the oldest organism we can study using evolutionary methods,” Goldman explained, “some of the genes in its genome were much older.” The team’s focus on universal paralogs – genes that appear in multiple copies across nearly all living organisms – provides a window into this earlier period. These genes aren’t simply conserved; they’ve been duplicated and diversified over billions of years, preserving a record of biological changes that occurred before the LUCA.

The concept of paralogs is illustrated by the human genome’s eight different hemoglobin genes, all derived from a single ancestral globin gene that existed approximately 800 million years ago. Repeated copying errors over vast stretches of time created these additional gene versions, each evolving to perform a specialized function. Universal paralogs, however, are far less common, suggesting their origins lie even further back in evolutionary history.

What sets universal paralogs apart is their widespread presence. Found in at least two copies in the genomes of almost all living organisms, their initial duplication is believed to have occurred before the emergence of the LUCA. This ancient duplication event means these genes have been passed down through countless generations, offering a unique opportunity to study life’s earliest forms.

“Due to this deep evolutionary coverage, the authors argue that universal paralogs are an important, but often overlooked, resource for studying the earliest history of life on Earth,” according to the research. The increasing practicality of this approach is driven by advancements in artificial intelligence and specialized AI hardware, which facilitate detailed analysis of ancient genetic patterns.

“Although there are very few universal paralogs that we know of,” Goldman stated, “they can provide us with a lot of information about what life was like before the time of the last universal common ancestor.” Fournier added, “The history of these universal paralogs is the only information we will have about these older cell lineages, and therefore we need to carefully extract as much knowledge from them as possible.”

The initial analysis focused on all known universal paralogs, revealing that these genes are involved in fundamental cellular processes: building proteins and transporting molecules across cell membranes. This suggests that protein production and membrane transport were among the earliest biological functions to evolve. These processes are essential for all known life, indicating their importance in the very beginnings of cellular organization.

Researchers at Oberlin College further investigated a universal paralog family involved in inserting enzymes and other proteins into cell membranes. By reconstructing the ancestral protein produced by the original gene, they found that it could still bind to cell membranes and interact with the protein-producing machinery. This suggests the ancient protein played a role in incorporating proteins into early membranes, providing clues about how primitive cells might have functioned.

The implications of this research extend beyond simply pushing back the timeline of life’s origins. It offers a new framework for understanding the conditions and processes that allowed life to emerge in the first place. By studying the functions of these ancient genes, scientists can begin to reconstruct the environment in which the LUCA evolved and the characteristics of the cells that preceded it.

Kaçar emphasized the potential for future discoveries, stating, “By following universal paralogs, we can connect the earliest stages of life on Earth with the tools of modern science. They give us the chance to turn the deepest unknowns of evolution and biology into discoveries that we can actually test.” The ultimate goal is to build a more complete picture of evolution leading up to the LUCA, shedding light on how life as we know it came to be.

The research team anticipates that continued advancements in computational tools will allow them to identify additional families of universal paralogs and study their ancient ancestors in greater detail. This ongoing work promises to unlock further secrets about the origins of life and the conditions that made it possible on Earth – and potentially, elsewhere in the universe.

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