CRISPR Origins Traced Back to LUCA

A recent British study at the University of Bristol indicates that the last universal common ancestor (LUCA) possessed an early form of the CRISPR-Cas immune system, dating back approximately 4.2 billion years, suggesting that CRISPR evolved just a few hundred million years after the planet formed.

By: Gorm Palmgren - Jul. 15, 2024

The last universal common ancestor (LUCA) refers to the most recent common ancestor from which all current life on Earth descended. It is the point on the tree of life from which the fundamental domains of Archaea and Bacteria diverged.

The presence of 19 class 1 CRISPR–Cas effector protein families, including types I (Cas3 and Cas10) and III (Cas7), in LUCA's genome highlights the ancient origins of CRISPR-based immunity. Although Cas1 and Cas2 were absent, suggesting an incomplete CRISPR system, LUCA's capability to deliver an RNA-based immune response underscores the system's deep evolutionary roots.

This ancestral CRISPR-Cas system likely played a role in RNA sensing and signal transduction, marking the beginning of cellular immune mechanisms against viruses.

"LUCA had this early immune system as a way of avoiding viruses," says Edmund Moody in a comment to Science magazine. He is first author of the study and a genomics expert at the University of Bristol, UK.

Figure 1. A reconstruction of LUCA, within its evolutionary and ecological context. a, A... — Figure 1. A reconstruction of LUCA, within its evolutionary and ecological context. a, A representation of LUCA based on our ancestral gene content reconstruction. Gene names in black have been inferred to be present in LUCA under the most-stringent threshold; those in grey are present at the least-stringent threshold. From Figure 3 in Moody et al., Nature Ecology & Evolution (2024), https://doi.org/10.1038/s41559-024-02461-1

The researchers compared the genomes of 700 modern microbes, using sophisticated genomic analysis tools to identify shared features that arose first. They constructed a phylogenetic tree using 57 marker genes from 350 bacteria and 350 archaea species, tracking gene duplications and mutations to estimate LUCA's timeline and ecological interactions.

LUCA was until recently thought to have lived approximately 3.5-3.8 billion years ago. Still, the new study suggests that it emerged far earlier, namely 4.2 billion years ago and just a few hundred million years after the planet formed.

"How evolution proceeded from the origin of life to early communities at the time of LUCA remains an open question, but the inferred age of LUCA compared with the origin of the Earth and Moon suggests that the process required a surprisingly short interval of geologic time," the authors conclude in their paper.

This comprehensive study not only pinpoints the early existence of the CRISPR-Cas system. It also suggests that LUCA possessed a relatively complex genome, indicating that it was a cellular organism with sophisticated metabolic and genetic systems similar to modern prokaryotes. The study also provides insights into LUCA's lifestyle, which included a diet of hydrogen gas and carbon dioxide.

The research was led by Edmund Moody and Philip Donoghue from the University of Bristol, with contributions from various international collaborators. It was published in Nature Ecology & Evolution on July 12.

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