Genome sequencing project reveals new secrets about cat evolution

Together with an interdisciplinary team of collaborators, researchers at the Texas A&M School of Veterinary Medicine & Biomedical Sciences (VMBS) have unearthed new information about the history of cat evolution. This information explains how cats, including well-known species like tigers, lions, and domestic cats, evolved into different species and sheds light on the relationship between various genetic changes in cats and survival skills like the ability to smell prey.

The effort, which was published today in Nature Genetics, compared the genomes of numerous cat species to help researchers understand why, compared to other animal groups like primates, cat genomes often feature less complicated genetic changes (such rearrangements of DNA segments). It also provided fresh information on the regions of the cat's DNA that are most prone to evolve quickly and their function in species differentiation.

Specializing in cat evolution, Dr. Bill Murphy is a professor of veterinary integrative biosciences at VMBS. "Our goal was to better understand how cats evolved and the genetic basis of the trait differences between cat species," Murphy stated. "In order to produce more comprehensive cat genomic maps, we sought to make use of certain novel technologies.

"Our findings will open doors for people studying feline diseases, behavior, and conservation," he stated. "They'll be working with a more complete understanding of the genetic differences that make each type of cat unique."

Different takes on a topic

The reason why feline chromosomes—cellular structures that carry the genetic information for characteristics like fur color, size, and sensory abilities—are more stable than those of other animal groups is one of the many mysteries the scientists were attempting to solve.

"We've known for a while now that cat chromosomes across species are very similar to each other," Murphy stated. For instance, there is very little genetic difference between domestic cats and lions. Compared to what is often observed in big apes, there seem to be considerably fewer duplications, rearrangements, and other forms of variation."

This type of genetic variety in the primate order has facilitated the evolution of several species, including great apes and humans.

"The great ape genomes tend to break and rearrange, and even human genomes have very unstable regions," Murphy stated. "These variations may predispose certain individuals to have genetic conditions, like autism and other neurological disorders."

Murphy discovered that the frequency of something called segmental duplications—DNA segments that are extremely close copies of other DNA segments found elsewhere in the genome—seems to be the key to this variance between cats and apes.

"Primate genome researchers have been able to link these segmental duplications to chromosome rearrangements," he stated. The likelihood of chromosomal rearrangements increases with the number of segmental duplications present in an individual's DNA, and so forth.

By analyzing the genomes of many different cat species, we found that whereas primates have seven times more segmental duplications than cats, cats only have a small percentage of these duplications compared to other animal groups. We think we now understand why cat genomes are more stable—that's a significant distinction," the speaker stated.

A needle with two helixes

Even while there aren't as many significant genetic rearrangements in the DNA of cats, there are still a lot of distinctions. Murphy and his associates now have a clearer understanding of which regions of the cat's DNA are responsible for these alterations, particularly those that characterize speciation, or the distinctions between species, thanks to their study.

"It turns out that there's a large region on the center of the X chromosome where most of the genetic rearrangements are happening," Murphy stated. "In fact, there's one specific repetitive element within this region called DXZ4 that evidence tells us is largely responsible for the genetic isolation of at least two cat species, the domestic and jungle cat."

Murphy refers to DXZ4 as a satellite repeat; rather than being a normal gene that codes for a physical characteristic such as fur color, it helps with the three-dimensional structure of the X chromosome and most likely contributed significantly to the speciation of cats.

"The exact process is still unknown, but by comparing the genomes of all these cats, we can estimate more accurately how quickly DXZ4 developed in one species relative to all the others. We have discovered that DXZ4 is one of the cat genome's fastest-evolving regions; it is changing at a rate that surpasses that of 99.5% of the entire genome," the scientist stated.

"Because of the rate at which it mutates, we were able to demonstrate why DXZ4 is probably linked to speciation," Murphy stated.

Identifying hidden genes

The scientists also discovered stronger connections between the quantity of olfactory genes, which control smell perception in cats, and variations in social behavior and how they interact with their environment by using new, extremely precise genome sequences.

"Since cats are predators who rely heavily on smell to detect their prey, their sense of smell is a pretty important part of who they are," Murphy stated. "We've long wanted to know how genetic diversity affects the ability of different cat species to smell in their various habitats since cats are a highly varied family.

"Lions and tigers have a pretty big difference between certain odorant genes involved in detecting pheromones, which are chemicals that different animals release into the environment to communicate information about identity, territory, or danger," he said.

"We believe that the main distinction between the two species is that tigers lead solitary lives whereas lions are very gregarious animals that live in family groupings. Because they are in close proximity to other lions, lions may be less dependent on pheromones and other odorants, as seen by the lower number of these genes in their genomes, the expert speculated.

In contrast, tigers must be able to locate potential mates and detect prey across vast distances.

"Tigers, in general, have large olfactory and pheromone receptor repertoires," Murphy said. "We think this is directly tied to the size of their territories and the variety of environments in which they live."

In contrast, a large variety of olfactory genes seem to have disappeared from domestic cats.

"If they don't have to travel as far to find what they need because they're living with people, it makes sense that natural selection wouldn't preserve those genes," he stated.

Murphy said that the odorant receptors from the fishing cat, a kind of wild cat native to Southeast Asia that has evolved to life in the water, are his favorite example from the study.

"We were able to show that fishing cats have retained many genes for detecting waterborne odorants, which is a pretty rare trait in terrestrial vertebrates," he stated. "All of the other cat species have lost these specific genes over time, but fishing cats still have them."

This new understanding of the cat olfactory genes was made possible by trio binning, a novel method of genome sequencing that enables researchers to read the most challenging parts of a genome.

Also, the new technique greatly simplifies the process of distinguishing paternal and maternal DNA.

"With trio binning, you can now take DNA from an F1 hybrid—an animal whose DNA is split 50-50 between parents of different species—and cleanly separate the maternal and paternal DNA, giving you two complete sets of DNA, one for each parent species," Murphy stated. "The process is much simpler, and the results are more complete."

Completing the gaps

The project's most significant finding is that, despite their numerous similarities, cat species differ from one another.

"These differences are showing us how these animals are perfectly suited for their natural environments," Murphy stated. For conservationists and other people trying to protect or restore species in their native environments, knowing that they are not interchangeable is important.

"For example, you can't assume that tigers from Sumatra and Siberia are the same," he stated. "Their environments are wildly different, and those tiger populations have likely developed specialized genetic adaptations to help them survive in these very different places."

It's also critical for scientists to recognize that the most challenging genomic regions to assemble could hold the key to comprehending vital physiological processes like immunity and reproduction.

Not all genes have been difficult to sequence and investigate, including those related to smell. Previous studies lack this sort of information since scientists have also had difficulty sequencing genes related to immunity and reproduction. Completing genome assemblies is important since it is difficult to research a genetic problem in people, cats, or any other animal without all the components "Murphy added.

For the time being, Murphy and his colleagues will keep using the most cutting-edge genome assembly and sequencing methods on cat genomes to add as much information as they can on the world of cats.

Wes Warren, a professor of genomics at the Bond Life Sciences Center at the University of Missouri, and Bill Murphy, a VMBS professor of veterinary integrative biosciences at Texas A&M, designed the project. Researchers from Louisiana State University, the Guy Harvey Oceanographic Center, the Institute for Systems Biology in Seattle, University College Dublin, and the University of Washington collaborated in other projects.