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Feline Genomes Offer Clues to Cat Traits, Domestication

NEW YORK (GenomeWeb) – A team led by researchers from Washington University, Texas A&M University, and the University of Missouri has used comparative genomics to search for genetic signatures associated with biological and behavioral features found in the domestic cat, Felis silvestris catus.

In a study published in the early, online edition of the Proceedings of the National Academy of Sciences yesterday, the researchers presented a new, high-quality reference genome for the domestic cat. By comparing this sequence to re-sequenced genomes for representatives from half a dozen other domestic cat breeds as well as two European wildcats (F. silvestris silvestris) and two Eastern wildcats (F. silvestris lybica), they uncovered signs of positive selection that seem to correlate with domestication, for example.

These included selective signals in and around genes believed to govern behaviors such as reward seeking, memory, and fear — perhaps due to the means by which humans incrementally nudged the felines toward a more domesticated lifestyle.

"Humans most likely welcomed cats because they controlled rodents that consumed their grain harvests," co-senior author Wesley Warren, a researcher based at the Genome Institute at Washington University, said in a statement. "We hypothesized that humans would offer cats food as a reward to stick around."

While past studies have found evidence for dog domestication stretching back some 30,000 years or more, cats appear to have been cohabitating closely with humans for only about 9,500 years.

As such, cats are "really only semi-domesticated," Warren said, noting that cats as we know them "only recently split off from wild cats, and some even still breed with their wild relatives."

Nevertheless, he and his colleagues did see genetic signs of domestication in F. silvestris catus when they established a new, high-quality cat reference genome and compared it with re-sequenced genomes from wildcats, domestic cats, and sequences from other animals.

As part of an ongoing effort to tap the cat genome as a source of information on cat biology and on hereditary and infectious diseases that affect both cats and humans, the researchers started by producing a high-quality cat genome assembly.

Using a combination of Sanger and Roche 454 sequencing methods, the team sequenced genomic DNA from Cinnamon, a female Abyssinian cat with a well-documented family pedigree.

Those reads were then stitched together to produce a 2.35 billion base reference genome, covered to an average depth of 14-fold, which contained almost 19,500 predicted protein-coding genes and nearly 1,900 non-coding RNAs.

With this reference assembly as a guide, the team re-sequenced six more domestic cat breeds — the Egyptian Mau, Maine Coon, Norwegian Forest, Birman, Japanese Bobtail, and Turkish Van — with Illumina instruments and pooled DNA from four to five purebred representatives per breed, in most cases. Pooled samples from four European or Eastern wildcats were sequenced separately, again using Illumina instruments.

When they compared wild and domestic cat sequences to one another and to the genomes of the dog, tiger, cow, and human, the study's authors saw signs of selection in the feline lineage that appear to square with cats' carnivorousness and hunting skills. These included positive selection patterns affecting genes involved in hearing, vision in low light, and lipid metabolism.

The cat genome appeared to house fewer smelling-related genes than the dog genome, consistent with differences in the animals' hunting methods. On the other hand, the cat genome was replete with genes believed to contribute to pheromone detection.

Although wild and domestic cats shared many genetic features, the team detected selection differences in genes associated with neural crest cell function and survival that appear to mediate reward-related behaviors in other animals.

Targeted sequencing on a larger group of domestic cats made it possible to narrow in on new mutations in a gene called KIT that appear to explain the characteristic white feet found in the Birman cat breed, the study authors added, noting that white coloring in general is another cat trait that has been linked to domestication.

Nevertheless, "[t]he number of genomic regions with strong signals of selection since cat domestication appears modest compared with those in domestic dogs," they wrote, "which is concordant with a more recent domestication history, the absence of strong selection for specific physical characteristics, as well as limited isolation from wild populations."