The village and street dogs represent a unique model of canine populations. In the absence of selective breeding and veterinary care, they are subject mostly to natural selection. Their analyses contribute to understanding general mechanisms governing the genetic diversity, evolution and adaptation. In this study, we analyzed the genetic diversity and population structure of African village dogs living in villages in three different geographical areas in Northern Kenya. Data obtained for neutral microsatellite molecular markers were compared with those computed for potentially non-neutral markers of candidate immunity-related genes. The neutral genetic diversity was similar to other comparable village dog populations studied so far. The overall genetic diversity in microsatellites was higher than the diversity of European pure breeds, but it was similar to the range of diversity observed in a group composed of many European breeds, indicating that the African population has maintained a large proportion of the genetic diversity of the canine species as a whole. Microsatellite marker diversity indicated that the entire population is subdivided into three genetically distinct, although closely related subpopulations. This genetical partitioning corresponded to their geographical separation and the observed gene flow well correlated with the communication patterns among the three localities. In contrast to neutral microsatellites, the genetic diversity in immunity-related candidate SNP markers was similar across all three subpopulations and to the European group. It seems that the genetic structure of this particular population of Kenyan village dogs is mostly determined by geographical and anthropogenic factors influencing the gene flow between various subpopulations rather than by biological factors, such as genetic contribution of original migrating populations and/or the pathogen-mediated selection. On the other hand, the study of oldest surviving dogs suggested a biological mechanism, i.e. a possible advantage of the overal heterozygosity marked by the the microsatellite loci analyzed.

Biology Centre Institute of Parasitology Czech Academy of Sciences České Budějovice Czech Republic

Ceitec VFU University of Veterinary and Pharmaceutical Sciences Brno Czech Republic

Centre for Integrated Genomic Medical Research University of Manchester Manchester United Kingdom

Department of Animal Genetics University of Veterinary and Pharmaceutical Sciences Brno Czech Republic

Department of Parasitology and Parasitic Diseases Faculty of Veterinary Medicine University of Agricultural Sciences and Veterinary Medicine Cluj Napoca Cluj Napoca Romania

Department of Pathology and Parasitology University of Veterinary and Pharmaceutical Sciences Brno Czech Republic

Vétérinaires Sans Frontières Czech Republic Brno Czech Republic

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Freedman AH, Gronau I, Schweizer RM, Ortega-Del Vecchyo D, Han E, Silva PM, et al. Genome sequencing highlights the dynamic early history of dogs. PLoS Genet. 2014; 10: 1–12. PubMed PMC

Vila C, Savolainen P. Multiple and ancienit origins of the domestic dog. Science.1997; 276: 1687–1689. PubMed

Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature. 2005; 438: 803–819. doi: 10.1038/nature04338 PubMed DOI

Von Holdt BM, Pollinger JP, Lohmueller KE, Han E, Parker HG, Quignon P, et al. Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature. 2010; 464: 898–902. doi: 10.1038/nature08837 PubMed DOI PMC

Larson G, Karlsson EK, Perri A, Webster MT, Ho SYW, Peters J, et al. Rethinking dog domestication by integrating genetics, archeology and biogeography. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109: 8878–8883. doi: 10.1073/pnas.1203005109 PubMed DOI PMC

Wang GD, Zhai W, Yang HC, Wang L, Zhong L, Liu YH, et al. Out of southern East Asia: the natural history of domestic dogs across the world. Cell Res. 2016; 26: 21–33 doi: 10.1038/cr.2015.147 PubMed DOI PMC

Botigué LR, Song S, Scheu A, Gopalan S, Pendleton AL, Oetjens M, et al. Ancient European dog genomes reveal continuity since the Early Neolithic. Nature Communications. 2017; 8:16082 doi: 10.1038/ncomms16082 PubMed DOI PMC

Leroy G, Verrier E, Meriaux JC, Rognon X. Genetic diversity of dog breeds: between-breed diversity, breed assignation and conservation approaches. Animal Genetics. 2009; 40: 333–334. doi: 10.1111/j.1365-2052.2008.01843.x PubMed DOI

Wayne RK, Nash WG, O'Brien SJ. Chromosomal evolution of the Canidae I. Species with high diploid numbers. Cytogenetics and Cell Genetics. 1987; 44: 123–133 doi: 10.1159/000132356 PubMed DOI

Wayne RK, Nash WG,O'Brien SJ. Chromosomal evolution of the Canidae II. Divergence from the primitive carnivore karyotype. Cytogenetics and Cell Genetics. 1987; 44: 134–141. doi: 10.1159/000132357 PubMed DOI

Li Y, Vonholdt BM, Reynolds A, Boyko AR, Wayne RK, Wu D-D, et al. Artificial selection on brain-expressed genes during the domestication of dog. Molecular Biology Evolution. 2013; 30: 1867–1876 doi: 10.1093/molbev/mst088 PubMed DOI

Ramirez O, Olalde I, Berglund J, Lorente-Galdos B, Hernandez-Rodriguez J, Quilez J, et al. Analysis of structural diversity in wolf-like canids reveals post-domestication variants. BMC Genomics. 2014; 15: 1–23. doi: 10.1186/1471-2164-15-1 PubMed DOI PMC

Shannon LM, Boyko RH, Castelhano M, Corey E, Hayward JJ, McLean C, et al. Genetic structure in village dogs reveals a Central Asian domestication origin. Proceedings of the National Academy of Sciences of the United States of America. 2015; 112: 13639–13644. doi: 10.1073/pnas.1516215112 PubMed DOI PMC

Galibert F, Quignon P, Hitte CH, André C. Toward understanding dog evolutionary and domestication history. Comptes Rendus Biologies. 2011; 334: 190–196. doi: 10.1016/j.crvi.2010.12.011 PubMed DOI

Boyko AR, Boyko RH, Boyko CM, Parker HG, Castelhano M, Corey L, et al. Complex population structure in African village dogs and its implications for inferring dog domestication history. PNAS. 2009;106: 13903–13908. doi: 10.1073/pnas.0902129106 PubMed DOI PMC

Brown SK, Pedersen NC, Jafarishorijeh S, Bannasch DL, Ahrens KD, Wu JT, et al. Phylogenetic distinctiveness of Middle Eastern and Southeast Asian village dog Y chromosomes illuminates dog origins. PLoS ONE. 2011; 6(12): e28496 doi: 10.1371/journal.pone.0028496 PubMed DOI PMC

Sacks BN, Brown SK, Stephens D, Pedersen NC, Wu JT, Berry O. Y chromosome analysis of dingoes and southeast Asian village dogs suggests a neolithic continental expansion from Southeast Asia followed by multiple Austronesian dispersals. Molecular Biology and Evolution. 2013; 30: 1103–1118. doi: 10.1093/molbev/mst027 PubMed DOI

Wan QH, Wu H, Fujihara T, Fang SG. Which genetic marker for which conservation genetics issue? Electrophoresis. 2001; 25: 2165–2176. PubMed

Irion DN, Schaffer AL, Grant S, Wilton AN, Pedersen NC. Genetic variation analysis of the Bali street dog using microsatellites. BMC Genet. 2005; 8: 6:6. PubMed PMC

Pedersen N, Liu H, Theilen G, Sacks B. The effects of dog breed development on genetic diversity and the relative influences of performance and conformation breeding. Journal of Animal Breeding and Genetics. 2013; 130: 236–248. doi: 10.1111/jbg.12017 PubMed DOI

Bigi D, Marelli SP, Randi E, Polli M. Genetic characterization of four native Italian shepherd dog breeds and analysis of th eir relationship to cosmopolitan dog breeds using microsatellite markers. Animal. 2015; 9: 1921–1928. doi: 10.1017/S1751731115001561 PubMed DOI

Radko A, Rubiś D, Szumiec A. Analysis of microsatellite DNA polymorphism in the Tatra Shepherd Dog, Journal of Applied Animal Research. 2017; 46: 254–256.

Kim K S, Tanabe Y, Park CK, Ha JH. Genetic variability in East Asian Dog using microsatellite loci analysis. The American Genetic Association. 2001; 92: 398–403. PubMed

Brouillette JA, Venta PJ. Within-breed heterozygosity of canine single nucleotide polymorphisms identified by across-breed comparison. Animal Genetics. 2002; 33: 464–467. PubMed

Ostrander EA, Wayne RK. The Canine genome. Genome Research. 2005; 15: 1706–1716. doi: 10.1101/gr.3736605 PubMed DOI

Quignon P, Herbin L, Cadieu E, Kirkness EF, Hedan B, Mosher DS, et al. Canine Population Structure: Assessment and Impact of Intra-Breed Stratification on SNP-Based Association Studie.s PLoS ONE. 2007; 12: e1324. PubMed PMC

Gray MM, Sutter NB, Ostrander EA, Wayne RK. The IGF1 small dog haplotype is derived from Middle Eastern gray wolves. BMC Biology. 2010; 8: 16 doi: 10.1186/1741-7007-8-16 PubMed DOI PMC

Bömcke E, Soyeurt H, Szydlowski M, Gengler N. New N method to combine molecular and pedigree relationships. Journal of Animal Science. 2001; 4: 972–978. PubMed

Helyar SJ, Hemmer-Hansen J, Bekkevold D, Taylor MI, Ogden R, Limborg MT, et al. Application of SNPs for population genetics of nonmodel organisms: new opportunities and challenges. Molecular Ecology Resources. 2011; 11: 123–136. doi: 10.1111/j.1755-0998.2010.02943.x PubMed DOI

Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, Zhu L, et al. A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs. Science. 2007; 316: 112–115. doi: 10.1126/science.1137045 PubMed DOI PMC

Jones P, Chase K, Martin A, Davern P, Ostrander EA, Lark KG. Single-nucleotide- polymorphism-based association mapping of dog stereotypes. Genetics. 2008; 179: 1033–1044. doi: 10.1534/genetics.108.087866 PubMed DOI PMC

Schoenebeck J, Hutchinson SA, Byers A, Beale HC, Carrington B, Faden DL, et al. Variation of BMP3 contributes to dog breed skull diversity. PLoS Genet. 2012; 8:e1002849 doi: 10.1371/journal.pgen.1002849 PubMed DOI PMC

Hayward JJ, Castelhano MG, Oliveira KC, Corey E, Balkman C, Baxter TL, et al. Complex disease and phenotype mapping in the domestic dog. Nat Commun. 2016; 22:10460. PubMed PMC

Mastrangelo S, Biscarini F, Auzino B, Ragatzu M, Spaterna A, Ciampolini R. Genome-wide diversity and runs of homozygosity in the “Braque Français, type Pyrénées” dog breed. BMC Res Notes. 2018; 11: 13 doi: 10.1186/s13104-017-3112-9 PubMed DOI PMC

Siddle KJ, Quintana-Murci L. The Red Queen's long race: human adaptation to pathogen pressure.Curr Opin Genet Dev. 2014; 29: 31–38. doi: 10.1016/j.gde.2014.07.004 PubMed DOI

Ortutay C, Vihinen M. Conserved and quickly evolving immunome genes have different evolutionary paths. Human Mutation. 2012; 33: 1456–1463. doi: 10.1002/humu.22125 PubMed DOI

Ollier WE, Kennedy LJ, Thomson W, Barnes AN, Bell SC, Bennett D, et al. Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis. Immunogenetics. 2001; 53: 669–673. doi: 10.1007/s002510100372 PubMed DOI

Kennedy LJ, Barnes A, Happ GM, Quinell RJ, Bennett D, Angles JM, et al. Extensive interbreed, but minimal intrabreed, variation of DLA class II alleles and haplotypes in dogs. Tissue Antigens. 2002; 59: 194–204. PubMed

Quinnell RJ, Kennedy LJ, Barnes A, Courtenay O, Dye CH, Garcez LM, et al. Susceptibility to visceral leishmaniasis in the domestic dog is associated with MHC class II polymorphism. Immunogenetics. 2003; 55: 23–28. doi: 10.1007/s00251-003-0545-1 PubMed DOI

Borgans JAM, Beltman JB, Boer RJD. MHC polymorphism under host-pathogen coevolution. Immunogenetics. 2004; 55: 732–739. doi: 10.1007/s00251-003-0630-5 PubMed DOI

Lazarus R, Klimecki WT, Raby BA, Vercelli D, Palmer LJ, Kwiatkowski DJ, et al. Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three US ethnic groups and exploratory case–control disease association studies. Genomics. 2003; 81: 85–91. PubMed

Prugnolle F, Manica A, Charpentier M, Guegan JF, Guernier V, Balloux F. Pathogen-driven selection and worldwide HLA class I diversity. Current Biology. 2005; 15: 1022–1027. doi: 10.1016/j.cub.2005.04.050 PubMed DOI

Bairagya BB, Bhattacharya P, Bhattacharya SK, Dey B, Dey U, Ghosh T, et al. (2008) Genetic variation and haplotype structures of innate immunity genes in eastern India Infection. Genetics and Evolution. 2008; 8: 360–366. PubMed PMC

Coppinger R, Coppinger L. Only Street Dogs Are Real Dogs. Nautilus. 2016; 16: 80–87.

Kennedy LJ, Barnes A, Short A, Brown JJ, Seddon J, Fleeman L, et al. Canine DLA diversity: 3 Disease studies. Tissue Antigens Supplement. 2007; 69: 292–296. PubMed

Shiel RE, Kennedy LJ, Nolan CM, Mooney CT, Callanan JJ. Major histocompatibility complex class II alleles and haplotypes associated with non-suppurative meningoencephalitis in greyhounds. Tissue Antigens. 2014; 84: 271–276. doi: 10.1111/tan.12365 PubMed DOI

Necesankova M, Vychodilova L, Albrechtova K, Kennedy LJ, Hlavac J, Sedlak K, et al. MYD88 and functionally related genes are associated with multiple infections in a model population of Kenyan village dogs. Molecular Biology Reports. 2016; 12: 1451–1463. PubMed

Spurgin LG, Richardson DS. How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proceedings of the Royal Society B-Biological Sciences. 2010; 277: 979–988. PubMed PMC

Waller R. Eecology, migration, and expansion in East-Africa. African Affairs. 1985; 336: 347–370.

Lamphear J. The people of the grey bull—The origin and expansion of the Turkana. Journal of African History. 1988; 29: 27–39.

Watsonjones DL, Macpherson CNL. Hydatid-disease in the Turkana district of Kenya. 6. Man dog contact and its role in the transmission and control of hydatidosis amongst the Turkana. Annals of Tropical Medicine and Parasitology. 1988; 82: 343–356. PubMed

D’Amico G, Mihalca AD, Domsa C, Albrechtová A, Sándor AD, Modrý D. Taming the beast: rabies control in the cradle of mankind. Geospatial Health. 2013; 7: 409–411. doi: 10.4081/gh.2013.98 PubMed DOI

Kennedy L, Carter SD, Barnes A, Bell S, Bennett D, Ollier B, et al. Interbreed variation of DLA-DRB1, DQA1 alleles and haplotypes in the dog. Veterinary Immunology and Immunopathology. 1999; 69: 101–111. PubMed

Kennedy LJ, Angles JM, Barnes A, Carmichael LE, Radford AD, Ollier WER, et al. (2007) DLA- DRB1, DQA1, and DQB1 alleles and haplotypes in North American gray wolves. Journal of Heredity. 2007; 98: 491–9. doi: 10.1093/jhered/esm051 PubMed DOI

Soutter F, Kennedy LJ, Oilier WER, Solano-Gallego L, Catchpole B. Restricted dog leucocyte antigen (DLA) class II haplotypes and genotypes in Beagles. Veterinary Journal. 2015; 203: 345–347. PubMed PMC

Excoffier L, Laval G, Schneider S. Arlequin (version 30) An integrated software package for population genetics data analysis. Evolutionary Bioinformatics Online. 2005; 1: 47–50. PubMed PMC

Slatkin M. Gene flow and geographic structure of natural populations. Science. 1987; 236: 787–792. PubMed

STATISTICA, v. 12, StatSoft, Inc, Tulsa, OK, USA; 2012. Available from: http://www.statsoft.com.

Felsenstein J. PHYLIP—Phylogeny Inference Package (Version 3.2). Cladistics. 1989; 5: 164–166.

Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000; 155: 945–959. PubMed PMC

Earl DA, VonHoldt BM. STRUCTURE HARVESTER: a website and program for visualizing STRUCTURE output and implementing the Evanno method. Conservation Genetics Resources. 2012; 4: 359–361.

Jakobsson M, Rosenberg NA. CLUMPP: a cluster matching and permutation program for dealing with label switching and multimodality in analysis of population structure. Bioinformatics. 2007; 23: 1801–6. doi: 10.1093/bioinformatics/btm233 PubMed DOI

Rosenberg NA. Distruct: a program for the graphical display of population structure. Molecular Ecology Notes. 2004; 4: 137–138.

Peakall R, Smouse PE. GenAlEx 65: genetic analysis in Excel. Population genetic software for teaching and research–an update. Bioinformatics. 2012; 28: 2537–2539. doi: 10.1093/bioinformatics/bts460 PubMed DOI PMC

Puja IK, Iron DN, Schaffer AL, Pedersen NC. The Kintamani dog: genetic profile of an emerging breed from Bali, Indonesia. Journal of Heredity. 2005; 96: 854–859. doi: 10.1093/jhered/esi067 PubMed DOI

Greyling LM, Grobler PJ, van der Bank HF, Kotze A. Genetic characterisation of a domestic dog Canis Familiaris breed endemic to South African rural areas. Acta Theriologica. 2004; 49: 369–382.

Porras-Hurtado L, Ruiz Y, Santos C, Phillips C, Carracedo A, Lareu MV. An overview of STRUCTURE: applications, parameter settings, and supporting software. Front Genet. 2013; 29: 98. doi: 10.3389/fgene.2013.00098. PubMed PMC

Zajc I, Mellersh CS, Sampson J. Variability of canine microsattellites within and between different dog breeds. Mammalian Genome. 1997; 8: 182–185 PubMed

Foulley JL, Ollivier L. Estimating allelic richness and its diversity. Livestock Science. 2006; 113: 296–301.

Kirk H, Freeland JR. Applications and Implications of Neutral versus Non-neutral Markers in Molecular Ecology. International Journal of Molecular Sciences. 2011; 12: 3966–3988. doi: 10.3390/ijms12063966 PubMed DOI PMC

Aguilar A, Roemer G, Debenham S, Binns M, Garcelon D, Wayne RK. High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101: 3490–3494. doi: 10.1073/pnas.0306582101 PubMed DOI PMC

Oliver MK, Lambin X, Cornulier T, Piertney SB. Spatiotemporal variation in the strength and mode of selection acting on the major histocompatibility complex diversity in water vole (Arvicola terrestris) metapopulations. Molecular Ecology. 2009; 18: 80–92. doi: 10.1111/j.1365-294X.2008.04015.x PubMed DOI

Grasso AN, Goldberg V, Navajas EA, Iriarte W, Gimeno D, Aguilar I, et al. Genomic variation and population structure detected by single nucleotide polymorphism arrays in Corriedale, Merino and Creole sheep. Genetics and Molecular Biology, 2014; 37: 389–395. PubMed PMC

Yang Z, Bielawski JP. Statistical methods for detecting molecular adaptation. Trends in Ecology and Evolution. 2000; 15: 496–502. PubMed PMC

Morris KM, Wright B, Grueber CE, Hogg C, Belov K. Lack of genetic diversity across diverse immune genes in an endangered mammal, the Tasmanian devil (Sarcophilus harrisii). Molecular Ecology Resources. 2015; 11: 123–136. PubMed

Niskanen AK, Kennedy LJ, Ruokonen M, Kojola I, Lohi H, Isomursu M, et al. Balancing selection and heterozygote advantage in major histocompatibility complex loci of the bottlenecked Finnish wolf population. Mol Ecol. 2014; 23: 875–89. doi: 10.1111/mec.12647 PubMed DOI

Angles JM, Kennedy LJ, Pedersen NC. Frequency and distribution of alleles of canine MHC II DLA- DQB1, DLA-DQA1 and DLA-DRB1 in 25 representative American Kennel Club breeds. Tissue Antigens. 2005; 66: 173–184. doi: 10.1111/j.1399-0039.2005.00461.x PubMed DOI

Kennedy LJ, Barnes A, Short A, Brown J, Lester S, Seddon J, et al. Canine DLA diversity: 1 New alleles and haplotypes. Tissue Antigen. 2007; 69: 272–288. PubMed

Runstadler JA, Angles JM, Pedersen NC. Dog leucocyte antigen class II diverdity and relationships among indigenous dogs of the island nations of Indonesia (Bali), Australia and New Guinea. Journal compilation. 2006; 68: 418–426. PubMed

Schierup MH, Vekemans X, Charlesworth D. The effect of subdivision on variation at multi-allelic loci under balancing selection. Genetical Research. 2000; 76: 51–62. PubMed

Hyeroba D, Friant S, Acon J, Okwee-Acai J, Goldberg TJ. Demography and health of "village dogs" in rural Western Uganda. Prev. Vet. Med. 2017; 137: 24–27. doi: 10.1016/j.prevetmed.2016.12.009 PubMed DOI PMC