Cat genomes look a lot like ours


The genome of a mouse is, structurally speaking, a chaotic place. At some point in its evolutionary past, the mouse shuffled its ancestral genome like a deck of cards, distorting the architecture that makes most other mammalian genomes look like, well, mammal. “I still see it as the biggest outlier,” Bill Murphy, a geneticist at Texas A&M University, told me. “It’s about as different from any other placental mammal genome you can find, kind of like it’s the moon, compared to everything else on Earth.”

Mouse genomes are still incredibly useful. Through years of painstaking tinkering, meticulous mapping, and an incredible amount of breeding, researchers have deciphered the murine genetic code so thoroughly that they can age animals up or down or change their susceptibility to cancer, findings that have big implications for humans. But the genomic disorder of the mouse makes it less suitable for research that could help us understand how our own genetic codes are packaged and stored. That’s why some researchers turned to other subjects for study, just one rung up the food chain.

It turns out that cats harbor genomes that look and behave remarkably like ours. “Other than primates, the cat-human comparison is one of the closest you can get,” Leslie Lyons, a feline genetics expert at the University of Missouri, told me of the organization of the cat. genome.

Lyons and Murphy, two of the world’s foremost experts in feline genetics, have a long-standing mission to strengthen the ranks in their small area of ​​research. In addition to the genetic architecture, cats share our homes, diets, behaviors, many of our microscopic parasites, and some of the chronic diseases including diabetes and heart problems that permeate Western life. “If we could begin to understand why these things happen in some cats, but not in others,” Lyons told me, maybe humans and felines could share a little more health. advantages also.

Feline genomes are now mapped essentially end-to-end, “with near-perfect sequence,” Lyons said, a feat researchers have only recently achieved with humans. Complete genomes create references – perfectly transcribed texts that scientists can browse, with no blank pages or erasures to thwart them. Cats can’t tell us when they’re sick. But more investment in feline genomics could pave the way for precision medicine in cats, in which veterinarians assess the genetic risk for different diseases and intervene as early as possible, giving them “a leap in diagnosis”. Elinor Karlsson, a vertebrate genomics expert at the Broad Institute, told me. Because humans and cats are plagued with some of the same illnesses, identifying their genetic business cards might be good for us as well. Cats can develop, for example, a neurological disorder similar to Tay-Sachs disease, “a disease that kills children,” Emily Graff, veterinary pathologist and geneticist at Auburn University, told me. But gene therapy appears to work wonders against the disease in cats, and Graff’s colleagues plan to adapt treatment for its analogues in children.

The cat genome could also fuel more basic science, Lyons told me. Essentially, all of the cells in our body contain identical genomes, but have extraordinarily different developmental fates. Researchers have been trying for decades to unravel the mechanisms behind this process, which forces cells to force some of their genes into dormancy while keeping others in frequent use. One of the most dramatic examples of this phenomenon is the silence of one of the two X chromosomes in female cells. “We still don’t have a good idea of ​​how Genoa be on and off, ”New York University geneticist South Pinglay told me. “It’s all a chromosome. “

Inactivation of X is what stains the calico layers. These cats are almost exclusively female, and must be genetic mutts: one of their X chromosomes carries an orange furry gene and the other a black one. In a given cell, only one chromosome remains awake. This decision comes early in a cat’s development, and the cells that separate from these lines stay true to the color chosen by their parental cells, creating large patches of color. “This helped us establish that the inactivated X chromosome was relatively stable and remained stable for many cycles of cell division,” Sundeep Kalantry, an X inactivation expert at the University of Michigan, told me. “This is why the calico cat has such a high place in X inactivation.”

Genomes can be so stubborn about inactivating X that they will hold their ground even after being moved around. other cells. The first cloned cat, named Carbon Copy, or CC for short, was genetically identical to a classic colored calico named Rainbow. But CC was born with only undertones of brown and white: she had, apparently, been created from a cell that had closed its orange X and refused to reverse the process.

Many vagaries of gene and chromosome silencing – their permanence or relative impermanence in different contexts, for example – are still being worked out in different species by researchers, including Kalantry, a photo of which the lab website features. captivating of a calico. But they have long known that the shape and structure of a genome, and the arrangement of genes within it, influences how content is expressed. It is believed that most of our genome is made up of annotations and embellishments that shape how the rest is read; DNA fragments can even twist, bend, and travel great distances to punctuate each other. This is a big area where cats can help us, Lyons told me: if their genes are organized like ours, maybe they’re regulated like ours too. “Maybe this is where cats can step in,” she said.

Some people may feel uncomfortable studying felines in the lab. But Murphy notes that a lot of genetic work can be done smoothly. His team have become very adept at extracting gobs of DNA from cat cheek cells, using small wire brushes that they twist in the mouths of animals.

There are huge benefits to working with popular pets as well: community members are often eager to contribute, either directly or through their vets. When cats get sick, researchers can sample them and, in many cases, help them regain health. “I would say about 90 percent of studies in cats are done on models of natural disease,” Murphy told me. And the cats that pass through Lyons’ lab in Missouri, she told me, are adopted after they retire from their scientific careers.

Mice are easy and inexpensive to breed and house in the lab, and they’re already a big step ahead in scientific research. Cats are unlikely to overtake them; they might not even outperform dogs, which are particularly keen working with humans, and I’ve done it intensively, said Gita Gnanadesikan, a canine researcher at the University of Arizona. As research volunteers, cats tend to be more sullen and reserved. (Dogs have drawbacks too. We know a lot about their genomes, but dog breeds have been so genetically siled that their populations “aren’t diverse, so they’re not as good a model for humans,” m ‘Karlsson said.)

But cats have their place, experts told me, as part of an entire menagerie of animals that humans would benefit from better understanding. “In genetics there is this tension: are you trying to learn all you can about a small number of organisms, or branch out and try to learn small details about a larger number of organisms. ‘cash? Gnanadesikan told me. “I think one of the answers to that is right… yes.”

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