No abstract

Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.Felis catus | domestication | genome T he domestic cat (Felis silvestris catus) is a popular pet species, with as many as 600 million individuals worldwide (1). Cats and other members of Carnivora last shared a common ancestor with humans ∼92 million years ago (2, 3). The cat family Felidae includes ∼38 species that are widely distributed across the world, inhabiting diverse ecological niches that have resulted in divergent morphological and behavioral adaptations (4). The earliest archaeological evidence for human coexistence with cats dates to ∼9.5 kya in Cyprus and ∼5 kya in central China (5, 6), during periods when human populations adopted more agricultural lifestyles. Given their sustained beneficial role surrounding vermin control since the human transition to agriculture, any selective forces acting on cats may have been minimal subsequent to their domestication. Unlike many other domesticated mammals bred for food, herding, hunting, or security, most of the 30-40 cat breeds originated recently, within the past 150 y, largely due to selection for aesthetic rather than functional traits.Previous studies have assessed breed differentiation (6, 7), phylogenetic origins of the domestic cat (8), and the extent of recent introgression between domestic cats and wildcats (9, 10). However, little is known regarding the impact of the domestication process within the genomes of modern cats and how this compares with genetic changes accompanying selection identified...

Lymphoma (lymphosarcoma or malignant lymphoma) is the most common neoplasm of the hematopoietic system of cats and reportedly the cat has the highest incidence for lymphoma of any species. A 21-year retrospective survey of feline lymphoma covering the period 1983-2003 was conducted with the patient database at the Veterinary Medicine Teaching Hospital (VMTH) at the University of California, Davis, School of Veterinary Medicine. This period comprises the post-feline leukemia virus (FeLV) era. Feline lymphoma historically has been highly associated with retrovirus infection. Mass testing and elimination and quarantine programs beginning in the 1970s and vaccination programs in the 1980s dramatically reduced the subsequent FeLV infection rate among pet cats. The results of this survey confirm a significant decrease in the importance of FeLV-associated types of lymphoma in cats. In spite of this decrease in FeLV infection, the incidence of lymphoma in cats treated at the VMTH actually increased from 1982 to 2003. This increase was due largely to a rise in the incidence of intestinal lymphoma, and to a lesser degree, of atypical lymphoma. A high incidence of mediastinal lymphomas in young Siamese or Oriental breeds also was observed, supporting previous studies. Associations of intestinal lymphoma and inflammatory bowel disease and diet should be further considered.

Sheep, mice, cattle, goats and pigs have all been cloned by transfer of a donor cell nucleus into an enucleated ovum, and now we add the successful cloning of a cat (Felis domesticus) to this list. However, this cloning technology may not be readily extendable to other mammalian species if our understanding of their reproductive processes is limited or if there are species-specific obstacles.

Precise comparisons of mammalian gene maps require common anchor loci as landmarks for conserved chromosomal segments. Using a computer script that automates DNA sequence database alignments, we designed 410 evolutionarily conserved primer pair sequences which are specific for anchor locus gene amplification from any mammalian species' DNA. Primer pairs were designed to span introns for polymorphism ascertainment, and to include sufficient exonic sequence (25-400 bp) to allow for gene identification. A total of 318 primer pairs were optimized for domestic cats, and 86% of the sequenced feline PCR products showed homology to the gene of primer origin. A screen of 20 mammals from 11 orders revealed that 35-52% of the 318 primers yielded a single PCR product without further optimization suggesting that nearly 75% can be optimized for any eutherian mammal.

Fifty-one specific pathogen-free (SPF) cats 10 weeks to 13 years of age were infected with a cat-to-cat fecal-oral passed strain of feline enteric coronavirus (FECV). Clinical signs ranged from unapparent to a mild and self-limiting diarrhea. Twenty-nine of these cats were FECV naïve before infection and followed sequentially for fecal virus shedding and antibody responses over a period of 8-48 months. Fecal shedding, as determined by real-time polymerase chain reaction (RT-PCR) from rectal swabs, appeared within a week and was significantly higher in kittens than older cats. FECV shedding remained at high levels for 2-10 months before eventually evolving into one of three excretion patterns. Eleven cats shed the virus persistently at varying levels over an observation period of 9-24 months. Eleven cats appeared to have periods of virus shedding interlaced with periods of non-shedding (intermittent or recurrent shedders), and seven cats ceased shedding after 5-19 months (average 12 months). There was no change in the patterns of virus shedding among cats that were excreting FECV at the time of a secondary challenge exposure. Four cats, which had ceased shedding, re-manifested a primary type infection when secondarily infected. Cats with higher feline coronavirus (FCoV) antibody titers were significantly more likely to shed virus, while cats with lower titers were significantly less likely to be shedding. Twenty-two kittens born to experimentally infected project queens began shedding virus spontaneously, but never before 9-10 weeks of age. Natural kittenhood infections appeared to be low grade and abortive. However, a characteristic primary type infection occurred following experimental infection with FECV at 12-15 weeks of age. Pregnancy, parturition and lactation had no influence on fecal shedding by queens. Methylprednisolone acetate treatment did not induce non-shedders to shed and shedders to increase shedding.

The diaspora of the modern cat was traced with microsatellite markers from the presumed site of domestication to distant regions of the world. Genetic data were derived from over 1100 individuals, representing 17 random-bred populations from five continents and 22 breeds. The Mediterranean was reconfirmed to be the probable site of domestication. Genetic diversity has remained broad throughout the world, with distinct genetic clustering in the Mediterranean basin, Europe/America, Asia and Africa. However, Asian cats appeared to have separated early and expanded in relative isolation. Most breeds were derived from indigenous cats of their purported regions of origin. However, the Persian and Japanese bobtail were more aligned with European/American than with Mediterranean basin or Asian clusters. Three recently derived breeds were not distinct from their parental breeds of origin. Pure breeding was associated with a loss of genetic diversity; however, this loss did not correlate with breed popularity or age.

Recent advances in gene mapping technologies have led to increased emphasis in developing representative genetic maps for several species, particularly domestic plants and animals. These maps are being compiled with two distinct goals: to provide a resource for genetic analysis, and to help dissect the evolution of genome organization by comparing linkage relationships of homologous genes. We propose here a list of 321 reference anchor loci suitable for comparative gene mapping in mammals and other vertebrate classes. We selected cloned mouse and human functional genes spaced an average of 5-10 centiMorgans throughout their respective genomes. We also attempted to include loci that are evolutionarily conserved and represented in comparative gene maps in other mammalian orders, particularly cattle and the domestic cat. We believe that the map may provide the basis for a unified approach to comparative analysis of mammalian species genomes.