Cat and Human Genomes

Welcome back. Do you remember when former President Trump was stricken with COVID-19? One of the treatments to speed recovery was the antiviral drug remdesivir. A few years earlier, researchers with the University of Missouri-Columbia’s College of Veterinary Medicine had learned that remdesivir was effective in curing cats of a coronavirus-induced disease, feline infectious peritonitis. That opened the door for them to consider the drug for treating humans with COVID-19. Why? Because the receptors for the virus are similar between cats and humans.

Lest you think that was an anomalous or lucky connection, It turns out that cats are more genetically similar to humans than nearly any other mammal. And that similarity can potentially facilitate the expansion of genomic medicine for both cat and human healthcare.

The human genome—some 20,000 to 25,000 genes in 23 pairs of chromosomes in each cell (from www.genomicsengland.co.uk/understanding-genomics/what-is-a-genome/).

Before I go any further, it’s probably best to mention that genomics is the branch of molecular biology concerned with the structure, function, evolution and mapping of genomes--the complete set of genes or genetic material, composed of DNA, that’s present in a cell or organism; genome mapping identifies a series of landmarks in a genome; genome sequencing spells out the order of every DNA base in a genome; and as for DNA bases, there are more than 3 billion base pairs of DNA in the mammal genome.

Comparative Geonomics
Despite the progress in sequencing the human genome, advances in precision medicine rely on more than accurate and complete human genome sequences. Comparing sequences in different species and exploring what variations mean for the biology and disease of other species are significant in developing precision therapeutics. High-quality reference genomes, particularly of species where genomes are conserved (essentially unchanged throughout evolution) and follow the same order as that in humans, are essential.

Comparative genomics by National Human Genome Research Institute of the National Institutes of Health (graphic modified from www.genome.gov/about-genomics/fact-sheets/Comparative-Genomics-Fact-Sheet, August 2020).

Although the discovery of single-gene mutations that cause rare conditions progresses well with the human genome, most common diseases are more complex. Since these are common conditions affecting cats as well as humans, research comparing genomes can possibly help identify the genes and mechanisms causing the diseases.

Toward that end, a University of Missouri-led consortium developed a genome reference assembly from the genomes of 54 domestic cats, annotating the feline variations in the context of human genes. The team is continuing to expand that resource to obtain more accurate genome assemblies that might identify novel variations responsible for traits and conditions of importance to animal and human genomic medicine.

“Dark Matter” DNA
One area of special interest is understanding the functions of “dark matter” DNA.

Of the 3 billion-plus base pairs of DNA that form the mammal genome, only 2% is coded into proteins that help our bodies perform natural functions. The other 98% of DNA--the so-called dark matter DNA--is not fully understood but might include regulatory elements that switch our genes on or off.

Finding regulatory sequences in the cat genome and potentially developing therapies to turn those sequences on or off would be a major breakthrough in managing genetic mutations.

Wrap Up
Whether loved or hated, cats are often undervalued by the scientific community. Research in comparative genetics is proceeding rapidly, and the genome match is such that cats could be the optimal species for advancing precision medicine, especially for inherited diseases that affect both cats and humans.

Henry, dreaming about comparing his genome with Noah’s (photo by Noah Philipson).

There is ample justification for the University of Missouri-led consortium to believe that feline genomics holds great potential and promise for advancing human medicine and mammalian biology.

Thanks for stopping by.

P.S.
Genomics:
www.genome.gov/about-genomics/fact-sheets/A-Brief-Guide-to-Genomics
www.genomicsengland.co.uk/understanding-genomics/what-is-a-genome/
en.wikipedia.org/wiki/Genomics
Comparative geonomics:
www.genome.gov/about-genomics/fact-sheets/Comparative-Genomics-Fact-Sheet
en.wikipedia.org/wiki/Comparative_genomics
Review of feline genomic medicine and consortium research in Trends in Genetics journal: www.cell.com/trends/genetics/fulltext/S0168-9525(21)00142-6
Article on review on EurekAlert! website: www.eurekalert.org/news-releases/923830
Review of feline genome assembly in PLOS Genetics journal: journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008926
Article covering both feline genome reviews on Genetic Engineering & Biotechnology News website: www.genengnews.com/insights/cat-in-the-lab-feline-genomes-fuel-precision-medicine/