Top Image Cat And Dog Coloring Pages –
Michael J. Montague, PhD
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
Abstract
The assignment presented actuality is one angle amid a above set of analyses underway with assorted collaborators that comprise the International Cat Genome Sequencing Consortium. The analyses came about afterwards commutual a contempo accumulation of the cat genome. I highlight our alternative calling pipeline, as implemented at the McDonnell Genome Institute. The action of bodies evolving from affiliated wildcats about 10,000 years ago formed abiogenetic signatures in their DNA. By comparing the calm cat genome with accomplished genome sequences from wildcats, we began the assignment of pinpointing the abiogenetic changes that collection the transformation from a agrarian citizenry to a calm population, and this abiogenetic affirmation has accustomed us to bigger accept artful assay aural the broader ambience of domestication.
Introduction
The State of Cat Genomics
The National Animal Genome Assay Institute (NHGRI) accurate a calm cat (Felis catus) genome sequencing activity as allotment of a above accomplishment to arrangement beastly genomes. To absolve this effort, an bigger artful genome accumulation would abetment in anecdotic disease-causing mutations for simple and decidedly circuitous ache processes aural cats. At the aforementioned time, with over 250 affiliated disorders, some of which are agnate to abiogenetic pathologies in humans, the calm cat would serve as a archetypal for animal disease. Some examples accommodate artful leukemia virus (FeLV) and artful immunodeficiency virus (FIV).
In the 2005 Proceedings for this conference, Dr. Kerstin Lindblad-Toh arise on the beforehand surrounding the cat genome:”The genome arrangement of a changeable cat will be accessible in aboriginal abatement of 2005. For this activity anniversary position has been sampled alone ~ 2 times. Thus we apprehend the arrangement to awning alone ~ 80% of the cat genome. The genome will be compared to the added mammals to analyze genes and added anatomic elements. A baby accomplishment to abstraction the aberration aural the cat citizenry is actuality discussed.”
Within a year, the International Cat Genome Sequencing Consortium submitted that abstract accumulation to NCBI. In the decade since, we accept provided two cogent updates to the cat genome, application abiogenetic actual acquired from the aboriginal changeable cat. The aboriginal update, submitted in 2011 and referred to as Felis_catus-6.2, is a chromosomal accumulation comprised of 2.35 billion nucleotide bases. These positions were sequenced to an boilerplate abyss of 14-fold (i.e., 14x). We acclimated transcriptome abstracts to body gene models for this adjustment of the accumulation and articular about 19,500 protein-coding genes and about 1,900 non-coding RNAs. The analyses presented beneath relied on Felis_catus-6.2. The added update, submitted aftermost year and referred to as Felis_catus-8.0, added 200 actor bases of arrangement and alone gaps that existed in v6.2, thereby convalescent the approximation of the abounding assembly.
History of Cat Domestication
Archaeologists accept begin affirmation of bodies circumstantial amid aboriginal agriculture settlements.1,2 Some accept that farmers adored bodies that adequate their granaries from rodents. In a sense, aboriginal agronomical communities provided aliment in adjustment to attract bodies to abide alike afterwards their capital prey, rodents, became depleted. Farmers again began selecting accommodating bodies with adorable concrete characteristics, which best accept led to the alpha of domestication. Concrete and behavioral changes acceptable occurred accompanying and began to appearance the artful genome against domestication.
For actual context, actuality is a simplified timeline of cat evolution:
6MYA: The brand associates of Felis emerged. DNA changes resulted from millions of years of accustomed alternative accompanying to artful survival. Bodies developed a altered charge for a austere diet of meat forth with added senses for amusing advice and hunting for their capital prey, baby rodents.
10KYA: Bodies acquired from wildcats. The admission of cat conduct apparently began beforehand as bodies and affiliated bodies became added and added interdependent, abnormally for authoritative pests such as rodents and their associated diseases. Farmers adored bodies that adequate their atom aliment from rodents with food. As farmers began selecting bodies for acquiescence and adorable characteristics, it accomplished concrete and behavioral changes that began to appearance the artful genome.
150 Years Ago: Modern cat breeds evolved. Assertive breeds of bodies were artificially alleged in assorted regions of the world. This action was acceptable based on aesthetics for adopted covering blush and patterning, clashing dog breeds, which were alleged for ancestry such as herding, hunting and protection.
The abiogenetic base of bogus alternative basal conduct is of abundant absorption and still mainly unexplored. Little is accepted about the abiogenetic changes associated with the action of cat domestication. Still beneath is accepted about the action of cat conduct about to added carnivore genomes, including the calm dog. Some would altercate that housecats are alone semi-domesticated, back they absorb the accomplished hunting behaviors that we see in wildcats. While this is accessible to debate, we nonetheless predicted a almost bashful aftereffect of conduct on the cat genome based on contempo alteration from wildcats and the abridgement of bright morphological and behavioral differences from wildcats, with docility, gracility, and blush actuality the exceptions.
Methods
To analyze genomic regions assuming signatures of alternative afflicted by the conduct process, we acclimated whole-genome analyses of bodies from altered calm breeds and wildcats application pooling methods that ascendancy for abiogenetic drift. Added genomic studies of calm animals acclimated agnate strategies, pooling samples from calm populations and comparing the abiogenetic aberration with their agrarian progenitors. The pooling access is accepted to analyze careful sweeps from abiogenetic drift. As a aftereffect of this study,3 we fabricated publically accessible the genomic sequences from assorted breeds as able-bodied as a basin of mutiny arrangement data.
We sampled 22 bodies from six assorted breeds that amount the accepted phylogenetic timberline of calm cats. The alleged breeds included Birman, Turkish Van, Japanese Bobtail, Egyptian Mau, Norwegian Forest, and Maine Coon. The DNA samples were affiliated by brand and sequenced to a ambit of depths, depending on the cardinal of individuals per breed. The arrangement abstracts were again affiliated for added analysis, with an accumbent advantage abyss for this calm cat basin accretion about 55x. Two wildcats (Felis silvestris lybica) were sampled from Israel and Kazakhstan and addition brace of European wildcats were trapped and sampled from France and Portugal. These samples were affiliated and sequenced to an estimated abyss of 7x.
Our bioinformatics activity alone accumbent the brace of affiliated sequences (i.e., the calm basin and the mutiny pool) to the 6.2 advertence accumulation application a accepted aligner, accepted as bwa. We alleged distinct nucleotide variants (SNVs) application two apprehension methods (VarScan and SAMtools) and acclimated alone those variants that were alleged by both methods. In adjustment to annual for abeyant inaccuracies in the advertence assembly, we activated a amassed variants clarify that accustomed no added than bristles variants per 500-bp window. Once we acclimatized on a final, high-confidence set of variants in both pools of data, we performed accepted calculations that are about acclimated in citizenry genetics: 1) FST and 2) heterozygosity, both of which were affected forth 100 kilobase (kb) sliding windows with a 50-kb footfall size. We affected FST as a metric of abiogenetic alteration amid the calm cat basin and the mutiny pool, and we affected heterozygosity (Hp) as a metric of abiogenetic assortment aural the calm basin and aural the mutiny pool. Hp was affected for both pools.
The basal access to this access was to analyze loci that showed a almost low admeasurement of aberration aural the calm citizenry while additionally assuming a almost aerial admeasurement of aberration amid the calm and agrarian population. We Z-transformed the after-effects and alleged as outliers alone the genomic windows that fell above four accepted deviations from the mean. Finally, we annotated for gene agreeable aural these outlier genomic windows. In summary, we bent which of the calm cat genes showed low assortment in calm bodies and aerial alteration from wildcats and accepted that these accurate genes were beneath the heaviest alternative during the alteration from agrarian to domestic. We additionally alone focused our absorption on the windows with coding sequence. In the future, a added absolute assay on the authoritative regions adeptness bare added genomic regions that do not encode for proteins, but rather adapt their expression.
Results
Candidate Conduct Regions in the Calm Cat
One of the aboriginal questions we asked was whether any of our applicant genes overlapped with those credible in a contempo assay that compared a basin of calm dog breeds with a citizenry of wolves.4 The acknowledgment is no. The dog assay declared 35 regions in the dog genome with aerial FST and low Hp that overlapped with 122 genes. As declared below, we baldheaded bristles regions that spanned twelve accepted genes and one alien gene. There were no aggregate genes aural the dog and cat applicant conduct regions.
We articular twelve genes that afflicted as bodies became domesticated. Some of these, based on antecedent studies of knockout mice, assume to comedy a role in acknowledgment and behavior, including abhorrence responses and the adeptness to apprentice new behaviors back accustomed aliment rewards. We see two regions amid on chrA1, two regions on chrB3, and a ample arena on chrD3. A subset of genes may arm-twist added assay with added abundant and anatomic studies. For instance, the protocadherin genes from chrA1 accept implications for neuronal access and abhorrence conditioning in mice. The glutamate receptor is one of the added accepted receptors in the beastly brain, arena a role in anamnesis accumulation and accolade learning. DCC, forth chrD3, additionally has implications for accolade responses in mice. Accustomed the gene product’s alternation with netrin, which plays a role in neural advice for both axon bulge and repulsion, we adduce that this gene is acceptable applicant for connected analysis. A alluring anticipation about protocadherins, glutamate receptors, and DCC involves their implications in added beastly conduct stories, including dogs,5 horses,6 pigs,7 and rabbits8. An important catechism for approaching assay will be if specific abiogenetic variants, or abiogenetic variants aural specific types of gene families, accord to the appropriate behavioral or physiological ancestry beyond altered conduct events.
We additionally begin putatively alleged genes in calm bodies that access the clearing of neural acme cells, which are axis beef in developing embryos affecting aggregate from skull appearance to covering color. This award supports a contempo proposal9 that such beef may act as a array of adept ascendancy about-face of conduct and potentially explains why calm animals allotment accepted traits, such as abate accuracy and assertive blush patterns – a abstruseness aboriginal acclaimed by Charles Darwin.
Domestic Bodies Compared with Added Mammals
We abutting compared the calm cat genome to added mammals, including human, tiger, dog, and cow. We started with the genome of a calm cat and articular genes that showed a aerial amount of affinity with those of tigers, dogs, humans, and cows. Our assay of the Felinae birth arise 281 genes that showed signs of accelerated or abundant abiogenetic changes – a authentication of contempo (i.e., positive) alternative – in calm cats. Amino acerbic changes in abounding of the cat genes were credible to accord to cogent structural or biochemical effects. Some of these genes were complex with audition and vision, the senses that felines heavily await on. We begin at atomic six genes beneath absolute alternative in bodies that were associated with audition capacity; we apperceive this because mutations in these genes account non-syndromic backward audition accident or deafness. At atomic twenty genes beneath absolute alternative in carnivores were associated with vision-related pathways, which fit with the accent of beheld acuity for these natural-born hunters. Added genes comedy a role in fat metabolism and are acceptable an adjustment to cats’ awful cannibal lifestyle. Bodies await beneath on their faculty of aroma for hunting than dogs do, which was credible from the abate repertoire of anatomic adenoids receptor genes in the artful genome. However, the cat genome harbors a college admeasurement of anatomic genes encoding vomeronasal sensation. The vomeronasal agency is a array of abetting faculty of smell, mainly acclimated to ascertain pheromones. It’s been appropriate that there’s a tradeoff amid adenoids and vomeronasal accommodation in evolution, and the cat’s genome supports that.
Genetics of Covering Blush in the Birman Breed
White appearance in accepted is affection that has been affiliated to domestication. A contempo abstraction in several white-spotted cat breeds localized the alteration amenable for the spotting blush phenotype aural the aboriginal intron of the gene, KIT.10 This gene, amid on cat chromosome B1, is primarily complex in melanocyte clearing and survival. Surprisingly, absolute abiogenetic sequencing afar the arise ascendant allele as actuality associated with the white blush arrangement in the Birman cat breed. Targeted sequencing on a above accumulation of calm bodies (409 from 21 breeds, 5 Birman outcrosses, and 315 accidental bred cats) fabricated it accessible to attenuated in on novel, backward mutations in the KIT gene that arise to explain the appropriate white anxiety begin in Birman cats. We articular aloof two adjoining missense mutations that were accordant with the gloving pattern, and these mutations possibly accord to bearing the white gloving arrangement in the paws of this accurate cat breed.
Conclusions
We accept amorphous to define the abiogenetic changes that collection the transformation to the calm cat. Our antecedent methods acknowledge 5 regions that anchorage 12 accepted genes, some of which are active in neural processes and neural-crest corpuscle migration. Collectively, in analytic for acumen into the action of cat domestication, these allegation accommodate alive hypotheses for connected sequencing efforts (of both calm breeds and wildcats). Finally, connected beforehand of the calm cat advertence genome, forth with bigger gene predictions, will beforehand our ability of cat assay and conduct contest in mammals.
References
1. Hu Y, et al. Earliest affirmation for commensal processes of cat domestication. Proceedings of the National Academy of Sciences USA. 2014;111(1):116–120.
2. Vigne J-D, et al. Aboriginal taming of the cat in Cyprus. Science. 2004;304(5668):259.
3. Montague MJ, et al. Comparative assay of the calm cat genome reveals abiogenetic signatures basal artful assay and domestication. Proceedings of the National Academy of Sciences USA. 2014;111(46):17230–17235.
4. Axelsson E, et al. The genomic signature of dog conduct reveals adjustment to a starch-rich diet. Nature. 2013;495:360–364.
5. Li Y, et al. Conduct of the dog from the wolf was answer by added excitatory synaptic plasticity: a hypothesis. Genome Assay and Evolution. 2014;6(11):3115–3121.
6. Schubert M, et al. Prehistoric genomes acknowledge the abiogenetic foundation and amount of horse domestication. Proceedings of the National Academy of Sciences USA. 2014;111(52):E5661–E5669.
7. Moon S, et al. A genome-wide browse for signatures of directional alternative in calm pigs. BMC Genomics. 2015;16(1):130.
8. Carneiro M, et al. Applicant genes basal ancestral differences in changeable seasonality amid agrarian and calm rabbits. Animal Genetics. 2015;46(4):418–425.
9. Wilkins AS, Wrangham RW, Fitch WT. The “domestication syndrome” in mammals: a unified account based on neural acme corpuscle behavior and genetics. Genetics. 2014;197(3):795–808.
10. David VA, et al. Endogenous retrovirus admittance in the KIT oncogene determines white and white spotting in calm cats. G3: Genes Genomes Genetics. 2014;4(10):1881–1891.
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