Genomic signatures reveal new evidences for selection of important traits in domestic cattle.

We investigated diverse genomic selections using high-density single nucleotide polymorphism data of five distinct cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-known genes such as KIT, MC1R, ASIP, GHR, LCORL, NCAPG, WIF1, and ABCA12, we found evidence for a variety of novel and less-known genes under selection in cattle, such as LAP3, SAR1B, LRIG3, FGF5, and NUDCD3. Selective sweeps near LAP3 were then validated by next-generation sequencing. Genome-wide association analysis involving 26,362 Holsteins confirmed that LAP3 and SAR1B were related to milk production traits, suggesting that our candidate regions were likely functional. In addition, haplotype network analyses further revealed distinct selective pressures and evolution patterns across these five cattle breeds. Our results provided a glimpse into diverse genomic selection during cattle domestication, breed formation, and recent genetic improvement. These findings will facilitate genome-assisted breeding to improve animal production and health.

[1]  Tad S Sonstegard,et al.  Genome wide CNV analysis reveals additional variants associated with milk production traits in Holsteins , 2014, BMC Genomics.

[2]  D. Bickhart,et al.  A genome-wide association study of calf birth weight in Holstein cattle using single nucleotide polymorphisms and phenotypes predicted from auxiliary traits. , 2014, Journal of Dairy Science.

[3]  Leif Andersson,et al.  Current perspectives and the future of domestication studies , 2014, Proceedings of the National Academy of Sciences.

[4]  M. Goddard,et al.  Selection for complex traits leaves little or no classic signatures of selection , 2014, BMC Genomics.

[5]  D. Bickhart,et al.  Assessing signatures of selection through variation in linkage disequilibrium between taurine and indicine cattle , 2014, Genetics Selection Evolution.

[6]  R. Nielsen,et al.  Classic Selective Sweeps Revealed by Massive Sequencing in Cattle , 2014, PLoS genetics.

[7]  G. Chillemi,et al.  Signatures of selection in five Italian cattle breeds detected by a 54K SNP panel , 2014, Molecular Biology Reports.

[8]  D. Bickhart,et al.  A genome-wide survey reveals a deletion polymorphism associated with resistance to gastrointestinal nematodes in Angus cattle , 2014, Functional & Integrative Genomics.

[9]  M. Förster,et al.  A genome-wide scan for signatures of differential artificial selection in ten cattle breeds , 2013, BMC Genomics.

[10]  D. Bickhart,et al.  Genomic divergence of zebu and taurine cattle identified through high-density SNP genotyping , 2013, BMC Genomics.

[11]  M. P. Heaton,et al.  Worldwide Patterns of Ancestry, Divergence, and Admixture in Domesticated Cattle , 2013, PLoS genetics.

[12]  Holly C. Beale,et al.  Derived variants at six genes explain nearly half of size reduction in dog breeds , 2013, Genome research.

[13]  Hongen Zhang,et al.  RCircos: an R package for Circos 2D track plots , 2013, BMC Bioinformatics.

[14]  F. Schenkel,et al.  Genome-wide association study for birth weight in Nellore cattle points to previously described orthologous genes affecting human and bovine height , 2013, BMC Genetics.

[15]  H. Blum,et al.  Novel Insights into the Bovine Polled Phenotype and Horn Ontogenesis in Bovidae , 2013, PloS one.

[16]  F. Schenkel,et al.  Study of whole genome linkage disequilibrium in Nellore cattle , 2013, BMC Genomics.

[17]  Li Jiang,et al.  Genome-Wide Detection of Selective Signature in Chinese Holstein , 2013, PloS one.

[18]  K. Lindblad-Toh,et al.  The genomic signature of dog domestication reveals adaptation to a starch-rich diet , 2013, Nature.

[19]  E. G. Cothran,et al.  Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds , 2013, PLoS genetics.

[20]  G. Chillemi,et al.  Identification of a Short Region on Chromosome 6 Affecting Direct Calving Ease in Piedmontese Cattle Breed , 2012, PloS one.

[21]  D. Gianola,et al.  A High Resolution Genome-Wide Scan for Significant Selective Sweeps: An Application to Pooled Sequence Data in Laying Chickens , 2012, PloS one.

[22]  M. Groenen,et al.  Strong signatures of selection in the domestic pig genome , 2012, Proceedings of the National Academy of Sciences.

[23]  Christopher R. Gignoux,et al.  Limited Evidence for Classic Selective Sweeps in African Populations , 2012, Genetics.

[24]  Bertrand Servin,et al.  Detecting Signatures of Selection Through Haplotype Differentiation Among Hierarchically Structured Populations , 2012, Genetics.

[25]  J. Eder,et al.  SNP-based association mapping of the polled gene in divergent cattle breeds. , 2012, Animal genetics.

[26]  H. Blum,et al.  Bovine Polledness – An Autosomal Dominant Trait with Allelic Heterogeneity , 2012, PloS one.

[27]  Mathieu Gautier,et al.  A Quasi-Exclusive European Ancestry in the Senepol Tropical Cattle Breed Highlights the Importance of the slick Locus in Tropical Adaptation , 2012, PloS one.

[28]  Alvaro G. Hernandez,et al.  Whole-genome resequencing of two elite sires for the detection of haplotypes under selection in dairy cattle , 2012, Proceedings of the National Academy of Sciences.

[29]  Larsson Omberg,et al.  Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies , 2012, PLoS genetics.

[30]  Bertrand Servin,et al.  Genome-Wide Analysis of the World's Sheep Breeds Reveals High Levels of Historic Mixture and Strong Recent Selection , 2012, PLoS biology.

[31]  K. Lindblad-Toh,et al.  A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies , 2012, PLoS genetics.

[32]  Timothy P. L. Smith,et al.  Association, effects and validation of polymorphisms within the NCAPG - LCORL locus located on BTA6 with feed intake, gain, meat and carcass traits in beef cattle , 2011, BMC Genetics.

[33]  P. Wiener,et al.  Deciphering the genetic basis of animal domestication , 2011, Proceedings of the Royal Society B: Biological Sciences.

[34]  Jonathan Pevsner,et al.  Inference of Relationships in Population Data Using Identity-by-Descent and Identity-by-State , 2011, PLoS genetics.

[35]  D. Gianola,et al.  Application of site and haplotype-frequency based approaches for detecting selection signatures in cattle , 2011, BMC Genomics.

[36]  Jacob A. Tennessen,et al.  Parallel Adaptive Divergence among Geographically Diverse Human Populations , 2011, PLoS genetics.

[37]  Andreia J. Amaral,et al.  Genome-Wide Footprints of Pig Domestication and Selection Revealed through Massive Parallel Sequencing of Pooled DNA , 2011, PloS one.

[38]  M. DePristo,et al.  A framework for variation discovery and genotyping using next-generation DNA sequencing data , 2011, Nature Genetics.

[39]  M. Goddard,et al.  Polymorphic Regions Affecting Human Height Also Control Stature in Cattle , 2011, Genetics.

[40]  P. Phillips,et al.  Using Population Genomics to Detect Selection in Natural Populations: Key Concepts and Methodological Considerations , 2010, International Journal of Plant Sciences.

[41]  M. DePristo,et al.  The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. , 2010, Genome research.

[42]  M. Goddard,et al.  Genetic Architecture of Complex Traits and Accuracy of Genomic Prediction: Coat Colour, Milk-Fat Percentage, and Type in Holstein Cattle as Contrasting Model Traits , 2010, PLoS genetics.

[43]  P. Lichtner,et al.  A genome-wide scan for signatures of recent selection in Holstein cattle. , 2010, Animal genetics.

[44]  Paolo Ajmone-Marsan,et al.  Identification of Selection Signatures in Cattle Breeds Selected for Dairy Production , 2010, Genetics.

[45]  H. Imaoka,et al.  Fibroblast-derived HB-EGF promotes Cdx2 expression in esophageal squamous cells , 2010, Laboratory Investigation.

[46]  H. Hoekstra,et al.  Vertebrate pigmentation: from underlying genes to adaptive function. , 2010, Trends in genetics : TIG.

[47]  K. Lindblad-Toh,et al.  Whole-genome resequencing reveals loci under selection during chicken domestication , 2010, Nature.

[48]  Or Zuk,et al.  A Composite of Multiple Signals Distinguishes Causal Variants in Regions of Positive Selection , 2010, Science.

[49]  Richard Durbin,et al.  Fast and accurate long-read alignment with Burrows–Wheeler transform , 2010, Bioinform..

[50]  Stephen J. O'Brien,et al.  Genome-wide scans for footprints of natural selection , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[51]  R. Schnabel,et al.  Diversity and evolution of 11 innate immune genes in Bos taurus taurus and Bos taurus indicus cattle , 2009, Proceedings of the National Academy of Sciences.

[52]  Mathieu Gautier,et al.  A whole genome Bayesian scan for adaptive genetic divergence in West African cattle , 2009, BMC Genomics.

[53]  Tianhua Zhou,et al.  Inhibition of cytokinesis by overexpression of NudCL that is localized to the centrosome and midbody , 2009, Cell Research.

[54]  Catherine André,et al.  Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes , 2009, Science.

[55]  Mathieu Gautier,et al.  The Genome Response to Artificial Selection: A Case Study in Dairy Cattle , 2009, PloS one.

[56]  P. O’Reilly,et al.  Faculty Opinions recommendation of Genome-wide association study identifies eight loci associated with blood pressure. , 2009 .

[57]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[58]  N. Orr,et al.  A Genome Scan for Positive Selection in Thoroughbred Horses , 2009, PloS one.

[59]  M. Goddard,et al.  Mapping genes for complex traits in domestic animals and their use in breeding programmes , 2009, Nature Reviews Genetics.

[60]  Joseph K. Pickrell,et al.  Signals of recent positive selection in a worldwide sample of human populations. , 2009, Genome research.

[61]  D. Wagener,et al.  Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature , 2009, Proceedings of the National Academy of Sciences.

[62]  Robert D Schnabel,et al.  Genome-Wide Survey of SNP Variation Uncovers the Genetic Structure of Cattle Breeds , 2009, Science.

[63]  Timothy P. L. Smith,et al.  Development and Characterization of a High Density SNP Genotyping Assay for Cattle , 2009, PloS one.

[64]  Danielle G. Lemay,et al.  The bovine lactation genome: insights into the evolution of mammalian milk , 2009, Genome Biology.

[65]  M. Goddard,et al.  A genome map of divergent artificial selection between Bos taurus dairy cattle and Bos taurus beef cattle. , 2009, Animal genetics.

[66]  L. Andersson,et al.  Contrasting Mode of Evolution at a Coat Color Locus in Wild and Domestic Pigs , 2009, PLoS genetics.

[67]  J. Stolzenburg,et al.  KIT variants in bovine ovarian cells and corpus luteum , 2009, Growth factors.

[68]  Joanna L. Kelley,et al.  Positive selection in the human genome: from genome scans to biological significance. , 2008, Annual review of genomics and human genetics.

[69]  R. Nielsen,et al.  Patterns of Positive Selection in Six Mammalian Genomes , 2008, PLoS genetics.

[70]  B. Norris,et al.  A gene duplication affecting expression of the ovine ASIP gene is responsible for white and black sheep. , 2008, Genome research.

[71]  S. Hiendleder,et al.  Complete mitochondrial genomes of Bos taurus and Bos indicus provide new insights into intra-species variation, taxonomy and domestication , 2008, Cytogenetic and Genome Research.

[72]  Merete Fredholm,et al.  Highly effective SNP-based association mapping and management of recessive defects in livestock , 2008, Nature Genetics.

[73]  F. Rousset.  genepop’007: a complete re‐implementation of the genepop software for Windows and Linux , 2008, Molecular ecology resources.

[74]  D. MacArthur,et al.  Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans , 2007, Nature Genetics.

[75]  T. Leeb,et al.  Allelic Heterogeneity at the Equine KIT Locus in Dominant White (W) Horses , 2007, PLoS genetics.

[76]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[77]  G. Wray,et al.  Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution , 2007, Nature Genetics.

[78]  C. Bustamante,et al.  A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs , 2007, Science.

[79]  D. Kelsell,et al.  ABCA12 is the major harlequin ichthyosis gene. , 2006, The Journal of investigative dermatology.

[80]  Joshua M Akey,et al.  Genomic signatures of positive selection in humans and the limits of outlier approaches. , 2006, Genome research.

[81]  Shameek Biswas,et al.  Genomic insights into positive selection. , 2006, Trends in genetics : TIG.

[82]  M. Georges,et al.  The Role of the Bovine Growth Hormone Receptor and Prolactin Receptor Genes in Milk, Fat and Protein Production in Finnish Ayrshire Dairy Cattle , 2006, Genetics.

[83]  M. Akiyama.  Pathomechanisms of harlequin ichthyosis and ABCA transporters in human diseases. , 2006, Archives of dermatology.

[84]  Xiaoqi Liu,et al.  A mammalian NudC-like protein essential for dynein stability and cell viability. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[85]  J. Pritchard,et al.  A Map of Recent Positive Selection in the Human Genome , 2006, PLoS biology.

[86]  Carlos Bustamante,et al.  Genomic scans for selective sweeps using SNP data. , 2005, Genome research.

[87]  C. Drögemüller,et al.  Fine mapping of the polled locus to a 1-Mb region on bovine Chromosome 1q12 , 2005, Mammalian Genome.

[88]  J. Weller,et al.  Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle. , 2005, Genome research.

[89]  M. Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[90]  M. Gautier,et al.  Mapping of a Milk Production Quantitative Trait Locus to a 420-kb Region on Bovine Chromosome 6 , 2005, Genetics.

[91]  Dana C Crawford,et al.  Evidence for substantial fine-scale variation in recombination rates across the human genome , 2004, Nature Genetics.

[92]  Lisa M. D'Souza,et al.  Genome sequence of the Brown Norway rat yields insights into mammalian evolution , 2004, Nature.

[93]  Imke Tammen,et al.  Quantitative trait loci mapping in dairy cattle: review and meta-analysis , 2004, Genetics Selection Evolution.

[94]  Leif Andersson,et al.  Domestic-animal genomics: deciphering the genetics of complex traits , 2004, Nature Reviews Genetics.

[95]  M. Stephens,et al.  Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data. , 2003, Genetics.

[96]  J. Weissenbach,et al.  Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. , 2003, Human molecular genetics.

[97]  M. Stephens,et al.  Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. , 2003, Genetics.

[98]  Michel Georges,et al.  Molecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition. , 2002, Genetics.

[99]  Pardis C Sabeti,et al.  Detecting recent positive selection in the human genome from haplotype structure , 2002, Nature.

[100]  David A. Magee,et al.  Genetic evidence for Near-Eastern origins of European cattle , 2001, Nature.

[101]  P. Donnelly,et al.  A new statistical method for haplotype reconstruction from population data. , 2001, American journal of human genetics.

[102]  Justin C. Fay,et al.  Hitchhiking under positive Darwinian selection. , 2000, Genetics.

[103]  P. Donnelly,et al.  Inference of population structure using multilocus genotype data. , 2000, Genetics.

[104]  M. Shriver,et al.  Microsatellite DNA variation and the evolution, domestication and phylogeography of taurine and zebu cattle (Bos taurus and Bos indicus). , 1997, Genetics.

[105]  J. Lenstra,et al.  Characterization, chromosomal localization, and genetic variation of the porcine heart fatty acid-binding protein gene , 1997, Mammalian Genome.

[106]  D. Bradley,et al.  Mitochondrial diversity and the origins of African and European cattle. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[107]  R. Schekman,et al.  Coat Proteins and Vesicle Budding , 1996, Science.

[108]  P. Sharp,et al.  Evidence for two independent domestications of cattle. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[109]  F. Tajima.  Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. , 1989, Genetics.

[110]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[111]  L. Quintana-Murci,et al.  From evolutionary genetics to human immunology: how selection shapes host defence genes , 2010, Nature Reviews Genetics.

[112]  Thomas J. Nicholas,et al.  From the Cover: Tracking footprints of artificial selection in the dog genome , 2010 .

[113]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[114]  Claude-Alain H. Roten,et al.  Theoretical and practical advances in genome halving , 2004 .

[115]  Mouse Genome Sequencing Consortium.  Initial sequencing and comparative analysis of the mouse genome , 2002, Nature.