Every animal alive today, from jellyfish to jaguars, carries in its chromosomes a kind of genetic scar tissue, traces of ancient mergers, breaks, and shuffles that occurred hundreds of millions of years ago and were apparently never undone. That is the central finding of a sweeping new study published in Science Advances, which analyzed 5,821 chromosome-scale genomes spanning 4,454 species and 19 animal phyla to reconstruct, in unprecedented detail, how animal chromosomes have changed — or stayed the same — since the dawn of the animal kingdom.

The study, led by Lehigh University’s Darrin Schultz while he was at the University of Vienna, and Arno Blümel, Dalila Destanović, Fatih Sarigol, and Oleg Simakov of the University of Vienna, draws on genome sequencing data that has exploded over the past decade, growing from just 45 chromosome-level animal genomes in 2015 to thousands available today. Using this trove, the team built what they call "evolutionary genome topology," a set of computational tools that let them compare genome architecture across enormous evolutionary distances — something that direct DNA sequence comparison usually cannot do once species have diverged for hundreds of millions of years.

“With my earlier work, I was sequencing the genomes of the animals and the close relatives of animals,” says Schultz, assistant professor of biological sciences. “We had some discoveries about how some of the more distantly related groups of animals are related to each other and to us. I saw that there is a big gap in our understanding of how animal genome evolution occurred over the entire 700 million years that animals have existed. And so, we developed methods on how to compare the genomes across the entire animal tree.”

The 29 building blocks of animal genomes

The researchers' work builds on the concept of "ancestral linkage groups," or ALGs. These are 29 sets of genes that appear to have traveled together on the same chromosomes since the last common ancestor of nearly all animals, an organism that lived more than 700 million years ago. Despite the astonishing diversity of body plans that have evolved since then, these 29 gene groupings still show up, in various combinations or preserved separately, across the animal tree of life.

“This is the first time that anybody has done an analysis of all animal genomes,” Schultz says. “People have done this before for subclades within animals, like big studies about birds, big studies about vertebrates. This is the first one that is at this scale.”

Chromosomes evolve mainly by fusing together, and sometimes by breaking apart. When two ancient chromosomes fuse, their genes can either stay in tidy, separate blocks or gradually intermix through a process in which chromosomal inversions shuffle genes from the two original chromosomes together over time. The study found that all 406 possible pairwise combinations of the 29 ancestral linkage groups have been sampled somewhere in the animal kingdom. This suggests that evolution has explored essentially every possible way to fuse two ancient chromosomes together, even if it hasn't explored every possible arrangement within them.

This has downstream consequences for how species diverge. By projecting genomes from thousands of species into a mathematical "space" that captures their overall chromosomal architecture, the researchers found that genomes cluster tightly by evolutionary relatedness. Close relatives sit near each other, while genomes with heavy rearrangement, such as fruit flies, mosquitoes, roundworms, and segmented worms called clitellate annelids, drift toward distant, distinct regions of that space. Even lineages that have independently undergone extreme genome scrambling — squid and octopuses, mosquitoes, and earthworm relatives, for example — do not converge on similar-looking genome architectures. Each clade appears to find its own idiosyncratic route away from the ancestral state, rather than all roads leading to the same destination.

Beyond simply cataloging which chromosomes fused with which, the team examined what happens at a finer scale. When genes from two previously separate chromosomes end up next to each other after a fusion event, do they just sit there or do they start interacting? The researchers found evidence for what they call "entanglement," cases where genes brought into proximity by ancient chromosomal mixing have developed stable, long-term physical and potentially regulatory relationships that persist across entire animal groups, sometimes for hundreds of millions of years.

One striking example involves two genes. One is involved in translation machinery, the other in cellular pH regulation. In most invertebrates, these genes sit on entirely different chromosomes. But in more than 90% of vertebrate species sampled, they've become tightly linked: positioned head-to-head, less than 5,000 base pairs apart. In humans, a shared genetic switch controls both genes together. The authors suggest these pairings, once formed, may be hard to undo. That could lock in new patterns of gene regulation, potentially driving the evolution of new traits. 

A resource for the field

Beyond its specific findings, the study represents a substantial infrastructure contribution to evolutionary biology. Schultz and his colleagues have developed a curated database spanning 59 percent of recognized animal phyla, along with open-source software tools that other researchers can use to explore chromosome evolution in their own study organisms.

The authors caution that their approach samples only roughly a quarter of the genes in a typical animal genome and emphasizes ancient, slow-evolving markers over clade-specific genes. Still, the work establishes a baseline timeline and rate for chromosomal change across animal history. It contributes to a foundation, the authors write, for understanding "how present-day genome configurations are consequences of evolution's past" and how they may constrain what evolutionary paths remain open in the future.

What’s next

This work connects with larger scale efforts in Schultz’s lab. The team combines field research, laboratory experiments, DNA analysis and computer-based genomics to understand how changes in chromosomes have shaped the animal kingdom.  They are also developing new tools, including open-source software, single-cell techniques and multi-omic approaches, to study how changes in genomes influence the way cells develop and specialize. Ultimately, this research may help scientists better understand how genome evolution relates to human disease.

Schultz is also a member of the Lehigh Oceans Research Center, which brings together researchers across disciplines to explore some of the ocean’s biggest questions, from deep-sea ecosystems and marine life to climate, chemistry, evolution, and the history of our planet. Students are part of this work, gaining hands-on experience while contributing to research that expands our understanding of the ocean. In Schultz's lab, that work includes deep-sea research with remotely operated vehicles, plankton trawling, and blue-water diving to study comb jellies, sponges, jellyfish, and other animal groups that are key to understanding the earliest splits in the animal family tree.

"We're especially excited to understand how genomes changed early in animal evolution and shaped the future direction of life on our planet," Schultz says. "We also want to know what that tells us about the 'rules of life' that govern how chromosomes change in evolution and disease."