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      Comparison of village dog and wolf genomes highlights the role of the neural crest in dog domestication

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          Abstract

          Background

          Domesticated from gray wolves between 10 and 40 kya in Eurasia, dogs display a vast array of phenotypes that differ from their ancestors, yet mirror other domesticated animal species, a phenomenon known as the domestication syndrome. Here, we use signatures persisting in dog genomes to identify genes and pathways possibly altered by the selective pressures of domestication.

          Results

          Whole-genome SNP analyses of 43 globally distributed village dogs and 10 wolves differentiated signatures resulting from domestication rather than breed formation. We identified 246 candidate domestication regions containing 10.8 Mb of genome sequence and 429 genes. The regions share haplotypes with ancient dogs, suggesting that the detected signals are not the result of recent selection. Gene enrichments highlight numerous genes linked to neural crest and central nervous system development as well as neurological function. Read depth analysis suggests that copy number variation played a minor role in dog domestication.

          Conclusions

          Our results identify genes that act early in embryogenesis and can confer phenotypes distinguishing domesticated dogs from wolves, such as tameness, smaller jaws, floppy ears, and diminished craniofacial development as the targets of selection during domestication. These differences reflect the phenotypes of the domestication syndrome, which can be explained by alterations in the migration or activity of neural crest cells during development. We propose that initial selection during early dog domestication was for behavior, a trait influenced by genes which act in the neural crest, which secondarily gave rise to the phenotypes of modern dogs.

          Electronic supplementary material

          The online version of this article (10.1186/s12915-018-0535-2) contains supplementary material, which is available to authorized users.

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          Most cited references139

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          Global variation in copy number in the human genome.

          Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.
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            The complete genome sequence of a Neandertal from the Altai Mountains

            We present a high-quality genome sequence of a Neandertal woman from Siberia. We show that her parents were related at the level of half siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neandertal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neandertals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high quality Neandertal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neandertals and Denisovans.
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              The genomic signature of dog domestication reveals adaptation to a starch-rich diet.

              The domestication of dogs was an important episode in the development of human civilization. The precise timing and location of this event is debated and little is known about the genetic changes that accompanied the transformation of ancient wolves into domestic dogs. Here we conduct whole-genome resequencing of dogs and wolves to identify 3.8 million genetic variants used to identify 36 genomic regions that probably represent targets for selection during dog domestication. Nineteen of these regions contain genes important in brain function, eight of which belong to nervous system development pathways and potentially underlie behavioural changes central to dog domestication. Ten genes with key roles in starch digestion and fat metabolism also show signals of selection. We identify candidate mutations in key genes and provide functional support for an increased starch digestion in dogs relative to wolves. Our results indicate that novel adaptations allowing the early ancestors of modern dogs to thrive on a diet rich in starch, relative to the carnivorous diet of wolves, constituted a crucial step in the early domestication of dogs.
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                Author and article information

                Contributors
                jmkidd@umich.edu
                Journal
                BMC Biol
                BMC Biol
                BMC Biology
                BioMed Central (London )
                1741-7007
                28 June 2018
                28 June 2018
                2018
                : 16
                : 64
                Affiliations
                [1 ]ISNI 0000000086837370, GRID grid.214458.e, Department of Human Genetics, , University of Michigan, ; Ann Arbor, MI 48109 USA
                [2 ]ISNI 0000 0001 2216 9681, GRID grid.36425.36, Department of Ecology and Evolution, , Stony Brook University, ; Stony Brook, NY 11794 USA
                [3 ]ISNI 000000041936877X, GRID grid.5386.8, Department of Biomedical Sciences, , Cornell University, ; Ithaca, New York, 14853 USA
                [4 ]ISNI 0000000086837370, GRID grid.214458.e, Department of Computational Medicine and Bioinformatics, , University of Michigan, ; Ann Arbor, MI 48109 USA
                Author information
                http://orcid.org/0000-0002-9631-1465
                Article
                535
                10.1186/s12915-018-0535-2
                6022502
                29950181
                8c5b1844-ec17-419c-954e-fc36a3bd8f95
                © Kidd et al. 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 February 2018
                : 23 May 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: R01GM103961
                Funded by: FundRef http://dx.doi.org/10.13039/100000051, National Human Genome Research Institute;
                Award ID: T32HG00040
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Life sciences
                domestication,canine,selection scan,neural crest,retinoic acid
                Life sciences
                domestication, canine, selection scan, neural crest, retinoic acid

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