Even though most of my posts on MassGenomics concern human genetics and genomics, today I’d like to highlight a milestone in another species, one that many humans care fiercely about. This guy:
Cat lovers, rejoice! This month in the Proceedings of the National Academy of Sciencs, Mike Montague, Wes Warren, and colleagues published the first complete reference genome for the domestic cat. Their analyses offer insights into the genetics underlying feline biology, evolution, and most recently, domestication.
The cat recently surpassed the dog as the most popular pet in the world, with a global population size estimated at 600 million. Many people credit ancient Egypt with cat domestication, but there’s archaeological evidence showing that cats and humans lived together 5,000 years ago in China, and ~9,500 years ago in Cyprus. In both cases, the new relationship seemed to arise when people turned to agriculture to feed themselves. It seems obvious what happened: farming and storing grains drew rodents, and rodents drew cats.
The path to domestication for cats differs from that of most other domesticated animals that were selectively bred for food (livestock), herding, hunting, or security (dogs). Most of the 30-40 cat breeds recognized today originated within the last 150 years, and were selected mainly for aesthetic traits rather than functional ones. That’s a fancy way of saying we bred cats to be pretty, not to be useful.
The Cat Genome
The 19 chromosomes in the reference cat genome (18 autosomes and an X-chromosome) span 2.35 billion base pairs. It contains about 19,500 protein-coding genes and 1,850 non-coding RNAs, numbers that are very similar to the dog. The authors first looked at the ~10,000 genes that had orthologs (matches in another species) in the tiger, dog, cow, and human genomes.
Genes Under Positive Selection
They searched in particular for genes under positive natural selection, and put those findings in context with what we know about cats relative to other carnivores.
Cats have the broadest hearing range among carnivores. There are at least six genes that look to be under positive selection in cats that are associated with hearing capacity; we know this because mutations in these genes cause nonsyndromic recessive hearing loss or deafness. At least 20 genes under positive selection in cats are associated with vision-related pathways, which fits with the importance of visual acuity for these natural-born hunters.
Felines are “crepescular” hunters, meaning that they’re most active in the twilight periods before sunrise and after sunset. Thus it was fascinating to see positive selection on genes like CHM and CNGB3, in which mutations can cause retinal diseases featuring night blindness (i.e. choroideremia and retinitis pigmentosa) in humans.
Cats rely less on their sense of smell for huntings than dogs do, which is apparent from the smaller repertoire of olfactory receptor genes in the feline genome. However, the cat ancestor had more genes encoding vomeronasal sensation. The vomeronasal organ is a sort of auxiliary sense of smell, mainly used to detect pheremones. It’s been suggested that there’s a tradeoff between olfactory and vomeronasal capacity in evolution, and the cat’s genome supports that: sense of smell was traded for pheremone detection, on which cats rely for social communication.
Wildcats and Domestication Genes
What about genes that might be involved in the domestication process? To search for these, the authors combined sequencing data from 22 cats, including both domestic and wildcat breeds. Wildcats (Felis silvestris) are small cats found in Africa, Europe, and parts of Asia. They tend to be larger than domestic cats, with longer legs and more robust bodies. There are numerous subspecies of wildcat, but they generally fall into one of three specialties:
- Forest wildcats, like the European wildcat.
- Steppe wildcats, whose ancestors migrated to the Middle East and tend to have smaller bodies, longer tails, and lighter fur.
- Bay or bush wildcats, which have paler coats and more defined patterns (stripes and spots).
As you might have guessed, house cats are thought to have been domesticated from those fancy-looking bay wildcats, probably an African subspecies.
When the authors looked for evidence of selection, they found regions harboring genes like:
- PCDHA1 and PCDHB4, which play a role in neural connection establishment/maintenance and fear conditioning.
- GRIA1, a glutamate receptor gene involved in associating stimulus with reward.
- DCC, encoding the netrin receptor, which is expressed in dopaminergic neurons. Knockouts of this gene in mice produced animals with defects in memory, behavior, and reward.
So it looks like cats chose to domesticate themselves because they noticed that, if they came in and helped out with the rodent control, we would reward them with food. And they stayed because they were afraid that we wouldn’t feed them if they remained in the wild. The last assertion might not be correct based on observations of my neighbor feeding strays, but please, no one tell the cats that.
More on Cats and Domestication
If you want more great stories about the cat genome and domestication, you’ll find good articles in Wired Magazine and the Washington Post. Senior author Wes Warren also appeared on NPR’s Science Friday last week.
Montague MJ, Li G, Gandolfi B, Khan R, Aken BL, Searle SM, Minx P, Hillier LW, Koboldt DC, Davis BW, Driscoll CA, Barr CS, Blackistone K, Quilez J, Lorente-Galdos B, Marques-Bonet T, Alkan C, Thomas GW, Hahn MW, Menotti-Raymond M, O’Brien SJ, Wilson RK, Lyons LA, Murphy WJ, & Warren WC (2014). Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication. Proceedings of the National Academy of Sciences of the United States of America PMID: 25385592