New tool enables phylogenomic analyses of entire genomes

Researchers led by electrical engineers at the University of California San Diego have developed a better way to perform the comparative analysis of entire genomes. This approach can be used to study relationships between different species across geological time scales.

This new approach is poised to unlock discoveries regarding how evolution has shaped present-day genomes and also how the tree of life is organized. The new method, named CASTER, is described in a paper published in Science on 23 January 2025.

CASTER is poised to offer biologists a far more scalable approach than state-of-the-art for comparing full genomes. This is especially relevant given the exploding number of sequenced genomes of both living and also extinct species. All these genomes are available for comparative study through phylogenomic analyses. CASTER provides interpretable outputs that will help biologists understand not only the species relationships but also the mosaic of evolutionary histories across the genome.

“Since the early 2000s, countless studies have claimed ‘genome-wide’ phylogeny reconstruction; however, these have been all based on subsampling regions scattered across the genomes, totalling only a small fraction of each full genome that is part of any given study. Analyzing all genomic positions while using complex models had seemed out of reach,” said Siavash Mirarab, an electrical engineering professor at UC San Diego and the corresponding author of the new paper in Science “What excites me is that we can now perform truly genome-wide analyses using every base pair aligned across species with widely available computational resources.”

“Arriving at this milestone required combined efforts from many disciplines, including statistics, computer science, and biology,” said Chao Zhang, the first author on the new Science paper. Zhang completed his PhD at UC San Diego in the Bioinformatics and Systems Biology program. He is now on the faculty of the University of Copenhagen.

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