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# 5Origins of the dog: Genetic insights into dog domestication
BRIDGETT M. VONHOLDT AND CARLOS A. DRISCOLL
# 3
https://doi.org/10.1017/9781139161800.003 Published online by Cambridge University Press 23 Bridgett M. vonHoldt and Carlos A. Driscoll 3.1 Introduction
Dogs are the oldest domesticated animal and today are second only to cats as the most popular pet in western societies (Boyko, 2011 ; Leonard et al ., 2006 ; Wayne and vonHoldt, 2012 ). The dog has
taken on many signifi cant roles in human society, ranging from companion, sentry, and hunting
partner to its more recent function as a model for understanding human disease. By exploring the genetic and evolutionary history of our canine companions, we can better understand not only the natural history of dogs but also our own evolutionary history. Inquiries into the dogs natural history are now enlightened by molecular and genetic data to
an overwhelmingly greater degree then they were 20 years ago when the first edition of this book
was published. This trend towards increasing molecular inference will certainly continue, though morphology and archaeology will remain vitally important in completing our understanding of the cultural context of the changes wrought by domestication.
# 3.2 The wolf, ancestor of the dog
The dog and its ancestor, the wolf ( Canis lupus ), belong to the family Canidae. The 34 living species
of canids are grouped into four clades: a red fox-like clade, a South American clade, a wolf-like
clade, and a clade comprising only the gray and island fox ( Urocyon cinereoargenteus and U. lit-toralis , respectively) (Lindblad-Toh et al ., 2005 ; Perini et al ., 2009 ) (Figure 3.1 ). Canids are found
in all terrestrial habitats and, with the human-assisted introduction of dogs and foxes to Australia
and New Zealand, Antarctica is now the only continent without a resident population. Currently,
seven species belong to the dog-like genus Canis (Figure 3.2 ), which arose nearly six million years ago (mya) in North America and, along with a number of other carnivore species, expanded into Eurasia (4 mya) via the Beringian land bridge, and subsequently into Africa (3 mya) (Wang &
Tedford, 2008 ). The archaeological record indicates that the modern-day gray wolf ( Canis lupus lupus ) evolved in Eurasia around 34 mya, re-invading North America about 500 000 years ago (Wang & Tedford, 2008 ). Supremely adaptable, the wolf inhabits nearly every habitat and environ-mental condition (Mech & Boitani, 2003 ). Wolves vary greatly in size depending on their environ-
mental distribution, from the gracile 13 kg wolves of the Middle Eastern deserts to the large robust individuals (over 78 kg) of the Arctic tundra. Members of the genus Canis vary in appearance, behavior and degree of sociality (Mech &
Boitani, 2003 ; Packard, 2003 ). Based on recent molecular genetic studies and corroborating mor-
phological evidence, it is now agreed that the sole ancestor of the dog is the gray wolf, Canis lupus .
Though this verdict settles hundreds of years of speculation on dog origins (e.g. Clutton-Brock,
1981 ; Darwin, 1868 ), resolving which particular group of wolves was directly ancestral to the dog still proves challenging (Ding et al ., 2012; Franz et al ., 2016; Freedman et al ., 2014 ; Pang et al ., 2009 ; Savolainen et al ., 2002 ; Shannon et al ., 2015 ; vonHoldt et al ., 2010 ; Wang et al ., 2016 ).
Establishing an evolutionary timeframe for the initial domestication process is similarly problem-
atic, though estimates based on archaeological records and mitochondrial DNA indicate 16 000 and
12 000 years ago, respectively (Clutton-Brock, Chapter 2 ; Larson et al ., 2012 ). The taxonomic status of the dog remains contentious in some quarters, with a minority calling for the dog to be listed as a separate species, Canis familiaris , while others consider it a subspecies of the gray wolf (i.e. Canis lupus familiaris ).
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24 Origins of the dog: Genetic insights into dog domestication
Island fox Gray fox Maned wolf Bush dog Darwins fox Hoary fox South American gray fox Pampas fox Sechuran fox Crab-eating fox Short-eared dog Culpeo (Andean fox) African wild dog Gray wolf Golden jackal Side-striped jackal Black-backed jackal Bat-eared fox Raccoon dog Corsac fox Red fox Arctic fox Kit fox Fennec fox Coyote Dhole Dog South American species Wolf-like canids Red fox-like species
Figure 3.1 Canidae phylogeny with estimated dates of divergence in millions of years indicated on the branches. (Adapted by permission from John Wiley & Sons: Journal of Evolutionary Biology
(Perini, F. A. et al ., The evolution of South American endemic canids, etc.), copyright 2009.) (A black and white version of
this fi gure will appear in some
formats. For the color version, please refer to the plate section.)
> https://doi.org/10.1017/9781139161800.003 Published online by Cambridge University Press
25 Bridgett M. vonHoldt and Carlos A. Driscoll 3.3 The human handprint: Canine domestication
Just what is meant by domestication? Domestic is a colloquial term applied to many animals habit-
ually used by humans or habituated to human places. Domestication, in contrast, is a biological process that leads to the development of unique humananimal relationships that vary greatly both in quality and intensity. To borrow a concept from ecology, we could describe the relationship that many people today believe they have with their dogs as a mutualistic one i.e. one in which both
parties benefit from the association. But we can also recognize doghuman relationships that might
be better described as commensal i.e. cases in which one member (the dog) benefits from the
association while the other is more or less unaffected. Both represent examples of domestication but clearly to different degrees. Domestication is fundamentally different from taming , which is the habituation of an individual animal to human presence. Domestication alters the genetic (and morphological) characteristics of a breeding population and, unlike taming, these changes are heritable (Coppinger et al ., 2009 ). The domestication of wolves was an evolutionary process that favored any heritable predisposition
to tameness in a restricted population of ancestral wolves when in close proximity to human pop-
ulations (see Box 3.1). Subsequently, the process of domestication mandates a degree of genetic isolation from the parent species in order to segregate alleles controlling the suite of behaviors and
morphology encompassing the domestication syndrome (see below). For our purposes here, domestic dogs are wolves that have undergone a process of selection, cru-
cially relating to behavior and cognition, but also including morphology and metabolism, which has
> Aus As ME Eu Af SAm NAm Red wolf (Canis rufus )Coyote (Canis latrans )Gray wolf ( Canis lupus )Gray wolf ( Canis lupus )Golden jackal (Canis aureus )Side-striped jackal (Canis adustus )Black-backed jackal (Canis mesomelas )Ethiopian wolf (Canis simensis )
> Figure 3.2
Species of Canis from the wolf-like clade and their current geographic distribution (IUCN, 2012 ).
Distributions may overlap. Wolves were historically widespread across the Old and New Worlds, with current fragmentation a result of humans. Abbreviations: Af, Africa; As, Asia; Aus, Australia; Eu, Europe; ME, Middle East;
NAm, North America; SAm, South America. (A black and white version of this figure will appear in some formats. For
the color version, please refer to the plate section.)
> https://doi.org/10.1017/9781139161800.003 Published online by Cambridge University Press 26 Origins of the dog: Genetic insights into dog domestication
resulted in heritable genetic changes in allele frequencies. There continues to be much debate and speculation as to how this selection process occurred but, either way, it is likely to have happened in a series of stages (Diamond, 2005 ; Driscoll et al ., 2009 ; Lord et al ., Chapter 4 ; Vigne, 2011; Zeder, 2012 ):
1. Selective affi liation of wolves with humans predisposed to tolerance and lower levels of aggres-
sion and fear in proximity to humans; a process shaped by a combination of natural selection and human acceptance. 2. Fitness advantages accrue to those wolves that reproduce successfully in, or in close proximity to, the human environment, probably reinforced by a degree of human provisioning (transition
from natural to unconscious artificial selection). 3. Early selection for utility leading to the initial emergence of primitive dogs by an unconscious process of artificial selection. 4. Prehistoric type formation based on landraces or specific utilities (e.g. coursing, baying, short legs, etc.) (a transition from unconscious to deliberate artificial selection).
5. Modern era of genetic isolation and rapid radiation of highly specialized breeds, often based on
physical conformation, rather than strict utility (methodical artificial selection). Not all domestic dogs have been subjected to all five of these stages. Some are best described as
semi-domestic in the sense that they have not been subjected to conscious selective breeding but have, due to long association with humans and their environment, and long reproductive isolation from their wolf ancestors, plainly become domestic animals (that is, they are clearly part of a human
landscape and are derived from it). Examples of such semi-domestic dogs include the dingo and
New Guinea singing dog, neither of which has been subjected to the kind of conscious selective breeding associated with the modern radiation (stages 45) but which have experienced the early stages of domestication (stages 13).
## Box 3.1 Natural versus artifi cial selection
Charles Darwin discussed artificial selection as an analogue of evolution by natural selection
(Darwin, 1868 ), but both selection processes require that the desired traits are heritable with
some more advantageous than others. Natural selection is the environmentally driven mecha-nistic process that works to preserve only the adaptive variants; artificial selection works in a
similar way, but with the key difference that humans determine which traits are to be passed on to the next generation of pups (Diamond, 2005 ; Driscoll et al ., 2009). Human-imposed selective breeding of only a subset of dogs shapes the canine population, shifting the frequen-
cies of morphological and behavioral traits. Therefore, the domestication of a species is an
evolutionary process accomplished through artificial selection.
The dingo has been isolated in Australia for approximately 5000 years (Larson et al ., 2012 ; Savolainen et al ., 2004 ). During this time, dingoes have evolved primarily through natural selection
post-domestication, since they have never been subjected to the highly managed breeding found
among modern purebred dogs. As a result, the dingo is still readily socialized or habituated to human
proximity and has, historically, participated in mutually beneficial hunting parties with Australian Aborigines, but it is also capable of living altogether independent of humans in self-sustaining
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27 Bridgett M. vonHoldt and Carlos A. Driscoll
populations. Dingoes have also experienced some admixture with modern domestic dogs following
the arrival of European colonists, leaving a genetic fingerprint that has infl uenced the interpretation
of their evolutionary history (Figure 3.3) (Larson et al ., 2012 ; Savolainen et al ., 2004 ). Likewise, the African village dogs recently described by Boyko et al . ( 2010 ) are a cryptic pop-ulation of dogs living in association with humans that have not experienced the artificial selection associated with modern breed formation. The term cryptic here refers to populations that are
morphologically indistinguishable from the surrounding population but which are still genetically distinct, indicating that some degree of genetic isolation is being enforced either ecologically or
geographically. As a result of the absence of conscious artificial selection on these semi-domestic
populations, some hypothesize that such dogs harbor a closer representation of the early, domestic dog genome, though this remains controversial.
Regardless of where wolf domestication occurred, the inter-specific bond between early dogs
and humans was probably loose enough to permit dogs to form transitory associations with local gray wolves (Anderson et al ., 2009; Randi, 2008; Vil and Wayne, 1999; Vil et al ., 2005). This fraternization allowed these dogs to hybridize with wolves, enriching the dog genome during early
phases of domestication, and thereby providing new genetic and phenotypic variants. A genome-wide genetic study has confirmed these secondary contacts with local wolf populations, providing
new sources of genetic diversity to the genomes of early dogs (vonHoldt et al ., 2010 ). Over suc-ceeding generations, dogs acquired important status in human society, and often received benefits from being part of the human pack, likely in the form of protection, access to resources, and
> 100,000 ya: Ancestral wolf population 13,00045,000 ya: Earliest dog fossils identified 12,0009,500 ya: Stone Age 5,000 ya: Dingoes to Australia circa 1800s: Victorian Era, Modern dog breed radiation Today Feral and semi-domesticated dog breeds (e.g. dingo) Modern dog breeds (>350 recognized)
> Dog Wolf
> Figure 3.3
Model for dog domestication.
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## Box 3.2 The Russian farm-fox experiment
In one of the most interesting experiments of the last century, silver foxes ( Vulpes vulpes )have undergone experimental domestication at a Russian breeding center in Siberia (Belyaev, 1969 ; Trut, 1999 ; Trut et al ., 2009 ). This farm-fox experiment provides some important
clues as to how domestication might have proceeded, and serves as a remarkable resource for understanding how selective breeding can shape phenotypes. The experiment was initiated in the 1950s by the scientist Dmitry Belyaev at the Russian
Academy of Sciencess Institute of Cytology and Genetics (Belyaev, 1969 ; Spady and Os-
trander, 2008; Statham et al ., 2011 ; Trut, 1999 ; Trut et al ., 2009 ). The goal was to selectively breed the foxes to become tamer. However, as the tame lineage of foxes were producing tamer kits, the researchers noticed physical changes in the foxes appearance: size variation increased; their coats became more diverse in coloration and fur structure (e.g. appearance of
wirehair and curly); ears flopped over; tails became shortened and curly, and females became
polyestrous, allowing for multiple litters per year (Trut, 1999 ). Many if not all of these traits
companionship. Dogs were quickly integrated into human culture, while breeding practices gradu-
ally shaped the dogs function and form with each successive generation.
# 3.4 The human cultural context of domestication
Domesticated dogs come from one or more lineages of gray wolves that have been modified by
chronic exposure to humans and human environments. A highly social species, the wolf relies upon
cooperative living and it is therefore easy to imagine that the first proto-dogs were born to wolves
that had a propensity to associate with or tolerate some degree of proximity to human groups. As these tolerant wolves reproduced, their pups inherited the genes for their parents temperament and
these proto-dogs established the first population of early dogs (see Box 3.2). The stories of these first
dogs can be deciphered from the fossil record and from the cultural context of human burial sites. It seems that, rather than being domesticated in direct association with Near Eastern agriculture
roughly 10 000 years ago, as were other species (e.g. cattle, goats, pigs, and sheep), the archeolog-ical record suggests that dogs may have appeared in an earlier hunter-gatherer past, and in a region
including Europe and eastern Siberia (Driscoll et al ., 2009; Crockford & Kuzmin, 2012; Germonpr
et al ., 2009; Ovodov et al ., 2011; Sablin & Khlopachev, 2002; Zeder, 2008) (Figure 3.3). However, in the Epipaleolithic (late Stone Age, ~ 15 kya), humans shifted towards a sedentary and eventually
agrarian-based society (Dayan, 1999 ; Morey, 1994 ). In these early civilizations humans were accom-panied by their dogs, presumably fulfilling various practical roles in local villages and fields, perhaps
serving as companions, and probably traded or bartered along trade routes (Sundqvist et al ., 2006). Dating these early dog populations can be challenging. Although dates may be derived from
genetic data by invoking a molecular clock, these analyses often result in large margins of error.
For this reason, archaeologists tend to rely on carbon dating of fossil remains. The challenge then is
in the differentiation of dog fossils from those of other closely related canine species (see Clutton-
Brock, Chapter 2 ).
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29 Bridgett M. vonHoldt and Carlos A. Driscoll
Figure 3.4 Tame-bred foxes have many physical and behavioral traits that are dog-like. This tame
adult fox is playing with a ball. Photograph courtesy of Anna Kukekova (see Spady and Ostrander, 2007).
have been noted in other domesticated species (including cattle, goats, pigs and sheep) and are
now referred to as the domestication syndrome (Driscoll et al ., 2009 ; Trut, 1999 ; Trut et al ., 2009 ) ( Table 3.1). Surprisingly, within 10 generations of selectively breeding the foxes for
tame behavior, they began to closely resemble domesticated dogs in both physical and behav-
ioral phenotypes (Figure 3.4 ) (Hare et al ., 2005 ; Kukekova et al ., 2010 ; Spady and Ostrander, 2008 ; Statham et al ., 2011 ).
Table 3.1 The domestication syndrome a suite of physical traits common to domesticated species (adapted from Driscoll et al ., 2009 ; Dobney and Larson, 2006 ; Hare et al ., 2005 ; Kukekova et al ., 2010 ; Spady and Ostrander, 2008 ; Trut, 1999 ; Trut et al ., 2009 ).
> Domesticated species Dwarf/giant size variety Piebald spotting White spotting Wavy or curly hair Curly or rolled tails Shortened tails Floppy ears Change in reproduction
Cat Cow Dog Donkey Goat Guinea pig Horse Mouse Pig Rabbit Sheep
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# 3.5 The canine genetic toolkit
In 2003, the entire nuclear DNA sequence from a Standard Poodle was made publicly available. In 2005 the genome of a different dog, a Boxer, was published (Kirkness et al ., 2003 ; Lindblad-Toh
et al ., 2005 ). From these DNA sequences researchers identified specific sites where nucleotides var-
ied within and between individuals. So far, over 2.5 million of these variants, referred to as single
nucleotide polymorphisms or SNPs, have been catalogued in the dog genome (Kirkness et al .,
2003 ; Lindblad-Toh et al ., 2005 ).
As researchers began exploring the genetics of domesticated animals, a few basic statistical meth-
ods were standardized in order to unravel the genetic history of species. Many researchers relied upon DNA sequence data and theories from evolutionary genetics to infer relationships or phylog-enies . For example, if the goal is to infer which population is the wild ancestor of a domesticate,
then the phylogenetic tree would provide a type of family tree in which the wild and domesticated
groups are expected to be more closely related then either is to more distantly related species. This
method has been applied towards understanding evolutionary relationships among wild and domes-
ticated species, including the dog (Dobney & Larson, 2006; Driscoll et al ., 2007 ; Frantz et al ., 2016 ; Parker et al ., 2004; Savolainen et al ., 2002; Shannon et al ., 2015 ; Vil et al ., 1997 , 2005 ; vonHoldt
et al ., 2010 ; Wang et al ., 2016 ; Zeder et al ., 2006 ).
# 3.6 Molecular evidence of the ancestral wolf populations
Moving a step beyond the analysis of archaeological remains from burial sites and dating of fossils through radioactive decay methods, advancing technologies allow for detailed genetic analyses of individuals from distinct geographic origins and evolutionary time periods. In addition to geography
and timing, we can also begin to assess the number of wolves involved in the early stages of domes-
tication (i.e. the number of founders), how many separate domestication events likely occurred, and the genetic changes that can be linked to the physical changes wolves experienced in the process of domestication. A number of recent molecular studies have sought to determine which geographic population(s)
of wolves is genetically closest to modern-day domestic dogs; doing so supplies strong inferential
evidence for the geographic and cultural origin of dogs. Several theoretical approaches have been employed. One early study was based on analyzing matrilineal mitochondrial DNA from a handful of Eurasian wolves and hundreds of dogs representing various geographic regions (Africa, America,
Europe, Asia, Siberia, and India) as well as ancestries (e.g. purebred, semi-domestic dogs, mixed
breed, stray, mongrels) (Savolainen et al ., 2002 ). By inferring phylogenetic relationships and assess-
ing genetic diversity, this and subsequent studies have concluded that all dogs share a common
ancestry with wolves from East Asia, specifically in the region south of the Yangtze River (Pang
et al ., 2009 ; Savolainen et al ., 2002 ; Wang et al ., 2016 ). The study relied upon measures of genetic diversity as an indication of the geographic center of domestication. Based on the assumption that as individuals disperse from a large population they take with them only a subset of the original genetic diversity, the source population is presumed to be more diverse than that found in the colonizing offshoots (Barrett & Schluter, 2008 ; Biswas & Akey, 2006 ; Innan & Kim, 2004 ).
An alternative approach has been to survey the genetic variation and genomic structure of prim-itive and semi-domestic dogs, such as the dingo, New Guinea singing dog, and the African village
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dog. The genomes of these dogs are often considered to represent surviving versions of ancestral
dog genomes, some of which exist in isolation from wild canids (e.g. dingoes and New Guinea singing dogs) while others may survive as endogamous, cryptically differentiated populations that do not currently interbreed with recently derived dog breeds, though they may have experienced
inter-breeding in the past (Boyko et al ., 2009 ). Additionally, village dogs thrive as free-roaming com-
mensals within local human communities and have not been subjected to strong selective breeding.
Therefore, a genetic survey of these unique dogs may provide insight into a putatively ancestral
dog genome. However, care needs to be taken to properly distinguish true village dogs (which may
have existed for millennia) from introduced free-roaming dogs of recent European derivation, since
results will likely be misinterpreted if these dogs are mistakenly included.
The collection and analysis of genome-wide single nucleotide polymorphism (SNP) data across village and semi-domestic dogs has revealed a surprising result. When the genetic diversity was assessed in African village and domesticated dogs from around the globe, researchers found com-
parable levels of diversity to that of East Asian dogs from previous studies, calling into question the view that dogs originated in East Asia (Boyko et al ., 2009 ; Shannon et al ., 2015 ). A subsequent study that genetically surveyed 85 dog breeds determined that wolves from the Middle East contributed
the most variation to the genome of the domestic dog, with other dog-specific genetic variants only
found in this wolf population (Gray et al ., 2010 ; Parker et al ., 2009 ; vonHoldt et al ., 2010 ). The
apparent association with this geographic region is not surprising since it tends to corroborate ear-
lier theories that most domesticated animals have at least one point of origin in the Fertile Crescent (Dayan, 1999 ; Driscoll et al ., 2009 ; Zeder, 2008 ; Zeder et al ., 2006 ) (see Box 3.3). Recently, Freedman et al . (2014) utilized whole genome sequencing to survey representative individuals from the three putative centers of wolf domestication China, the Near East, and
Europe in addition to genome sequences from the supposedly ancient, semi-domestic dog breeds, the Basenji and dingo. They inferred that numerous bottlenecks through dog domestication his-tory have occurred, as well as instances of post-divergence gene flow, with the initial process of
domestication estimated to have started around 11 00016 000 years ago, predating the agricultural revolution. Moreover, the study found that modern wolves form a monophyletic sister clade to domestic dogs, implying that the direct ancestor of dogs is extinct, impossibly confounding any attempt at resolving the geographic origin of dogs when examining only extant lineages. This result was recently corroborated by an independent study of a fossil dog specimen from a cave in the Altai Mountains of Siberia (Druzhkova et al ., 2013). This study analyzed the mtDNA from a
33 000-year-old Pleistocene fossil dog and identified that it showed an affinity with modern dogs
and prehistoric wolves from North America. Due to the lack of phylogenetic proximity with any contemporary wolf population, it is proposed that the population of wolves directly ancestral to modern day dogs is indeed extinct. Further support for a European origin of domestic dogs comes from Thalmann et al .s ( 2013 ) recent sequencing of mitochondrial genomes from ancient and mod-ern canids. Bayesian phylogenetic and dating analyses identified that all modern dogs are more
closely related to ancient European canids, with the onset of dog domestication occurring between
18 800 and 32 100 years ago. This domestication event, they propose, coincides with the evolution-ary time when humans preyed upon megafauna as hunter-gatherers. In fact, their findings suggest that the conditions for domestication are not unique. Many early lineages of proto-dogs were likely
initiated but with many failing to survive to modern day, thereby populating the fossil record with aborted episodes of domestication.
Most recently, genomic analyses have confirmed deep evolutionary divergence between two geo-
graphically disparate wolf populations (Fan et al ., 2016 ; Frantz et al ., 2016 ). Frantz and colleagues ( 2016 ) suggest this may represent two independent dog domestication events. They suggest that
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## Box 3.3 New World origins?
In the Americas, fossils reliably identified as dog are significantly younger (ca. 900010 000
ya) than those in the Old World (15 00033 000 ya) although dogs were common in the New
World at the time of European colonization (Clutton-Brock, Chapter 2 ; Larson et al ., 2012; Leonard et al ., 2002). An obvious question is whether these New World dogs represented a separate lineage of domesticated dogs (i.e. domesticated in the Americas from American wolves) or if they accompanied early humans in crossing the Bering land bridge, presumably
between 20 000 and 11 000 ya. To answer this question, DNA sequence of pre-Columbian
dog fossils from both the Old and New Worlds were analyzed and compared to modern day dogs and gray wolves. Phylogenetic analyses revealed that fossil New World dogs were
more closely related to the European-derived modern dog breeds and thus did not repre-
sent a unique and separate domestication (Goebel et al ., 2008; Leonard et al ., 2002; Waters
et al ., 2007). eastern dogs dispersed westward alongside their human counterparts between 6400 and 14 000 years ago. The arrival of these eastern dogs replaced the indigenous Paleolithic dog population in western Europe. This potential genetic replacement through admixture presents challenges for inferring the history of dog domestication.
# 3.7 Breeds
The origin and relationships among domesticated dog breeds, whose histories are often anecdotal or only partially documented, has been a persistent interest of genetic research long before the release of the dog genome sequence. Early natural historians considered each dog breed to be derived from a local canid population, be it wolf, coyote, jackal, or fox (Darwin, 1868 ). In Europe, dog breeds have existed since at least the 1300s (certainly even earlier accounts of distinct varieties have been described in classical Greek literature), mostly for hunting; a different dog breed was employed for each different quarry: badger hounds, wolfhounds, otter hounds, and deer hounds, for example.
Note, however, that this is not the first formation of dog varieties; sighthound-type coursing dogs and mastiff-type hunting dogs represent two breed types of antiquity (Clutton-Brock, 1981 and
Chapter 2 ). There was, at that time, no evidence of strong line breeding: dogs being bred to task in the fashion of a true working dog such that any dog with desirable qualities, regardless of parentage, was introduced into the line. By the mid 1800s, however, dog breeding was driven primarily by a focus on form rather than function. The Victorian view of what a breed should be changed to emphasize conformation and pedigree, and the weight given to actual functionality was often greatly lessened. This is where modern dog breeding has its roots. Breed organizations, such as the American Kennel Club (AKC), established
strict regulations to control breeding practices in order to achieve and preserve specific desired aes-thetics or function ( Figure 3.3 ), and virtually mandated the practice of line-breeding (Ritvo, 1989 ).
As universal breeding standards were applied, the number of dogs allowed to reproduce quickly
decreased and only show champions of a breed that possessed an outstanding award-winning record
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became popular sires. With the same champion being used many times in a pedigree, inbreeding was
frequently commonplace. A major consequence of this strong line-breeding practice is an increased occurrence of medical conditions and breed-specific diseases (see Hubrecht et al ., Chapter 14 ).
Because breeders could select mutations with obvious phenotypes (e.g. dwarfism, see below) to
include in their lineage, and because fanciers tend to select for the extremes of a phenotype, such breeding practices did allow for the rapid development of new sizes, shapes, colors, and behavioral features. As a result, there are currently about 175 distinct breeds recognized by the AKC, while over
350 breeds have worldwide recognition (Lindblad-Toh et al ., 2005 ; Parker et al ., 2004 ; Spady & Ostrander, 2008 ; Young & Bannasch, 2006 ). In an early genetic study designed to identify individual breed histories, researchers surveyed
the dog genome and identified repetitive DNA elements called microsatellites . Based on a survey
of 96 microsatellites in over 400 dogs representing 85 breeds, genetic relatedness-based measure-ments were used to cluster individual breeds into larger breed groups related in heritage, such as mastiff-related breeds, breeds convergent on the herding behavioral trait, and Nordic breeds, for
example (Parker et al ., 2004 ). These breed groups often represented major functional categories and have been confirmed by a more recent study (Parker, 2012 ; vonHoldt et al ., 2010 ) (Figure 3.5 ). However, inferences based on relatedness present a statistical challenge as the domesticated and wild groups can interbreed and produce viable offspring. Such hybridization events between distinct
lineages increase the levels of gene-sharing and genetic diversity, which will ultimately bias evolu-
tionary interpretations. Any analysis of dog breeds is complicated by the fact that breed histories are characterized by periods of admixture between lines, followed by strict line breeding. Any occurrence of mixing
across breeds will infl ate genetic diversity and skew the resulting inferences of ancestral relation-
ships (AKC, 2006 ; Parker et al ., 2004, 2010 ; Parker & Ostrander, 2005 ; Sutter & Ostrander, 2004 ).
Therefore, scientists must rely upon additional analytical methods if they are to avoid making incor-
rect inferences based solely on the measurement of genetic similarity and diversity. Studies of morphological changes as documented from archaeological and burial sites have described variations in skeletal sizes, proportions, and dentition, but assessing the genetic changes
in similar specimens will provide information about the molecular changes associated with artificial
selection under domestication (see Box 3.2).
# 3.8 Genetic studies: the evolution of dog morphology
Domesticated dogs display a breadth of phenotypic variability not observed in gray wolves, or
indeed in any other domesticated animal (Stockard, 1941 ). Conversely, signifi cant traits exist in
wolves that are lacking in their domestic derivatives. Female wolves, for example, experience one estrous cycle per year, with the pups reared in a pack consisting of relatives (e.g. siblings, cousins) in addition to unrelated adults that forego reproduction and provide regurgitated food for the pups (vonHoldt et al ., 2008 ). Upon maturation, pups disperse out of their natal pack in an attempt to find
a mate and potentially establish their own pack. Dogs, on the other hand, have had many of their natural history traits altered through the domestication process in a way that distinguishes them from their wild relatives (Spady & Ostrander, 2008 ; Statham et al ., 2011 ; Trut, 1999 ; Trut et al ., 2009 )
(see Box 3.2). Dogs reach sexual maturity more quickly than wolves (<1 versus 2 years, respec-
tively), and will continue to bark throughout their lives, a behavioral trait that is rare in adult wolves
(Clutton-Brock, 1981 ; Morey, 1994 ). Also, critical to dogs survival among humans is the reduction
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34 Origins of the dog: Genetic insights into dog domestication
of hunting impulses (at least in most breeds) that make it possible for dogs and domestic livestock to live together peacefully. With the development of genome resources in the past decade, many researchers have conducted
genome-wide analyses concomitantly and uncovered a large number of shared genomic regions across various dog breeds that are associated with typical dog-specific phenotypes; that is, the col-
lection of traits that make a dog (Akey et al ., 2010 ; Boyko et al ., 2010 ; Chase et al ., 2009 ; Freedman
et al ., 2016 ; Jones et al ., 2008 ). Surprisingly, it turns out that seemingly complex traits in dogs (e.g. body dimensions, dentition, skeletal proportions) are due to a small handful of genes that explain
> Coyote China Spain Middle East Near East Basenji Akita Chow-chow Dingo Sib.Husky Afghan Hound Saluki Am.Eskimo Samoyed Pomeranian Chihuahua Pekingese Shih-Tzu Brussels Griffon Pug Papillon Irish Water Sp. Brittany Sp. German Short-haired Ptr. Basset Hound Beagle Blood hound PBGV Dachshund Havanese Std. Poodle Toy Poodle Gt. Schnauzer Std. Schnauzer German Shep. Dog Boston terr. Boxer Bulldog French bulldog Mini. Bull terr. Staf. Bull terr. Glen of Imaal Bull mastiff Mastiff Jack Russell Briard Aust. terr. Cairn terr. Scottish terr. Norwich terr. Bernese Mtn. Dog Aust. Shep. Collie Shetland Sheep dog Border Collie Cardigan Corgi Pembroke Corgi Borzoi Scottish Deerhound Irish Wolfhound Greyhound Whippet It. Greyhound Ibizan Hound Kuvasz Old Eng. Sheep Dog Yorkshire terr. West Highland terr. Portuguese Water Dog Dob. Pin. Mini. Pin. American Cocker Sp. Eng.Cocker Sp. Eng. Springer Sp. Cavalier King Charles Sp. Shar-pei Alask. Malamute Italy Balkans, Eastern & Northern Europe St. Bernard Grt. Dane Rottweiler Golden Ret. Labrador Ret. Newfoundland Flat-coated Ret.
## Ancient Modern Mastiff-Terrier Mountain H e rd in g-S i g h t h ou ndWild
Figure 3.5 Breed phylogeny, where the colors of branches indicate a functional breed group: yellow, ancient breeds; brown, spitz breeds; black, toy breeds; blue, mastiff-like breeds; red; modern breeds; gray, wild canids; green, herding-sighthounds; purple, mountain breeds. Black bar indicates Toy breeds. Ancient breeds were as defined in vonHoldt et al . ( 2010 ) and Parker (2012 ). Dots on internal branches indicate >95%
confi dence. (Adapted from vonHoldt et al ., 2010 ; Parker, 2012 .) (A black and white version of this figure will
appear in some formats. For the color version, please refer to the plate section.)
> https://doi.org/10.1017/9781139161800.003 Published online by Cambridge University Press 35 Bridgett M. vonHoldt and Carlos A. Driscoll
each trait, unlike the hundreds of genes required for the expression of similar traits in humans and
non-domesticated animals (Flint & Mackay, 2009; Visscher, 2008 ; Voight et al ., 2006 ; Wellcome
Trust Case Consortium, 2007 ). Additional studies have focused on very specific traits that are shared among a handful of dog breeds. Here, we focus on three examples of trait-specific mapping efforts
and their evolutionary implications (see Box 3.4).
## Box 3.4 Gene mapping
Gene mapping is a method in which scientists search for particular gene variants that are statistically associated with a phenotype. In the case of diseases, such variants may serve as therapeutic targets for treatment. Mapping a gene variant in humans is a complex statistical challenge, often requiring genetic samples from thousands of individuals. The method relies upon a set of genetic markers located across the genome, and then testing these markers
statistically for a non-random association with a phenotype of interest, such as a disease
or physical trait, across individuals with the trait (case) and those lacking it (controls) (see also van den Berg, Chapter 5). Despite the high degree of line breeding (and lack of genetic diversity) in the dog genome, genetic variants will exist as a result of random mutations, a
subset of which are associated with specific phenotypes (e.g. disease, curly tail, pigmenta-
tion patterns). For example, consider a dog breed that segregates two phenotypes (e.g. a bull terrier of both the piebald and solid pigmented variety; see Barsh, 2007) (Figure 3.6). After locating and sampling a number of solid and piebald bull terriers, we would scan each of the 38 canine chromosomes in search for a region that is shared among all piebald bull terriers but lacking in the solid pigmented dogs. We could further improve our chances of locating
this genomic region if we expand our search to other breeds that segregate the piebald phe-
notype (Figure 3.6).
## 3.8.1 Domestic trait 1: How to make a toy
The initial stages of dog domestication resulted in a dog that was proportionally reduced in size, a distinct phenotype along the spectrum of dwarfism , or proportional reduction in size. Dwarfed dog
breeds are easily recognizable, and are collectively referred to as Toy breeds by the AKC based on the sharing of one distinguishing feature: miniature body size. The genetics behind body size varia-
tion was originally investigated in the Portuguese water dog, as this breed was recently established with detailed pedigree records and is sexually dimorphic (the female is smaller in size than the male) (Chase et al ., 2002 , 2005 , 2009 ). An initial genetic survey identified a large region (15 million bases or nucleotides long) on chromosome 15 containing the insulin-like growth factor 1 gene ( IGF1 ) that
was significantly associated with canine body size (Chase et al ., 2005 ). The function of this gene is well described in humans as a growth factor that regulates postnatal skeletal growth (Baker et al ., 1993 ; Laron, 2001 ; Yakar et al ., 2002 ).
To further understand how this gene region is associated with small body size, a follow-up fine-mapping analysis focused on the region in detail in search of a genetic change that produces
the trait of interest (body size) (Sutter et al ., 2007 ). The mapping study categorized dogs as giant (>30 kg) and toy (<9 kg) breeds based on breed standards and searched for a fragment of DNA
> https://doi.org/10.1017/9781139161800.003 Published online by Cambridge University Press
36 Origins of the dog: Genetic insights into dog domestication
sequence (referred to as a haplotype ) that was shared among all the toy individuals that was lacking in the giant dogs, in addition to the molecular signals of selection (e.g. lack of genetic diversity across the haplotype; Sutter et al ., 2007 ). A haplotype found only in toy dogs and lacking in giant dogs was nearly perfectly associated with small body size. Upon a closer investigation the IGF1
gene in toy dogs was found to contain a mutation, specifically an insertion of DNA that was absent
in the giant dogs IGF1 gene (Sutter et al ., 2007 ). The small-dog insertion was further surveyed across global wolf populations, in order to better understand its evolutionary history. The inser-tion was found only among toy dogs, and was absent from the wolf genome, confi rming that this mutation occured post-domestication and is a toy dog-specific genetic variant (Gray et al ., 2010 ). Interestingly, when looking at the larger genomic region containing the IGF1 gene, all domesticated dogs have closer kinship with Middle Eastern wolves than other wolf populations, corroborating the
earlier findings of genomic contribution (Gray et al ., 2010 ; vonHoldt et al ., 2010 ).
Piebald Boxer Non-piebald Boxer
Piebald (Cases) No gene region is shared across breeds Shared gene region No gene region shared Shared gene region No gene region shared A gene region is shared across breeds Solid (Controls) Piebald Bullterrier Non-piebald Bullterrier
> Boxer 1 Chromosome 20 Boxer 2 Boxer 7
Figure 3.6 Conceptual framework of gene mapping through association. Here, the trait being mapped is piebald coloration across two breeds, the boxer and the bull terrier. Each colored segment is considered a different allele or variant on the chromosome. (Adapted by permission from Macmillan Publishers Ltd: Nature Genetics
(Barsh, G.S., How the dog got its spots), copyright 2007 .) (A black and white version of
this fi gure will appear in some
formats. For the color version, please refer to the plate section.)
> https://doi.org/10.1017/9781139161800.003 Published online by Cambridge University Press 37 Bridgett M. vonHoldt and Carlos A. Driscoll
Only a handful of genes, when altered, result in the miniaturized version of a dog. A breeder can take advantage of this genetic variant with large phenotypic effect by crossing the miniature dog
with other non-miniature dogs in order to shop around this subset of size-altering genes. This strict nature of controlled dog breeding allows for goal-directed changes in phenotypes, as is the case for
the miniature breeds found today (Sutter et al ., 2007 ).
## 3.8.2 Domestic trait 2: How to make shortened limbs
Just as in the case of miniature-sized dogs, many short-legged breeds were created for various func-tional purposes, such as burrow hunting, traversing through thick brush, and finding scents low to the ground. Many genes (specifically growth factors ) have been described that help regulate overall body size and skeletal proportions in humans (Giustina et al ., 2008 ; Lefebvre & Bhattaram, 2010 ; Su et al ., 2008 ). However, only recently was the genetic basis of canine leg length uncovered from
a genetic screen of short-legged and regularly sized dogs. All dogs with the short-legged phenotype carried a single extra copy of the fibroblast growth factor 4 ( FGF4 ) gene, whose effects halted the elongation of the long bones in limbs during embryonic development (Parker et al ., 2009 ). This sec-ond full-length identical copy of FGF4 has a unique origin as a retrogene copy established through a gene duplication event called retrotransposition .
Specific types of DNA elements (a subset called retrotransposons ) can undergo self-replication,
with the new copy inserting into a new location in the genome (Cordaux & Batzer, 2009; Kazazian,
2004 ; McClintock, 1956 ). The replication process of retrotransposons can be at times error-prone, sometimes incorporating with their new copy bits of other DNA sequences. In the case of short-legged dogs, the retrotransposon copy contained the entire protein-coding sequence of the FGF4 gene and, upon inserting this copy over 30 million nucleotides away, was a new identical copy of the gene but
under new regulatory controls. Short-legged breeds then not only carry the original parental gene of
the parental FGF4 gene, but also an additional copy. Researchers also found that this new gene copy
functioned independently, with the over-expression of this new copy linked to the termination of long-
bone growth prematurely in development, producing short legs (Parker et al ., 2009). The part of the chromosome that contains the FGF4 retrogene copy was additionally surveyed
in wolves from across the globe in order to help infer when this retrogene was likely to have first inserted and the first short-legged dog appeared. Using the haplotype around the retrogene, the major finding is that all short-legged breeds, no matter where they originated geographically, share this same retrogene. Therefore, all short-legged dogs share a common ancestor with one origination event of this retrogene duplication and insertion, which has been passed around to various dog line-ages by deliberate cross-breeding.
## 3.8.3 Domestic trait 3: How to change hair type and structure
From smooth, long fur to coarse furnished (eyebrow and mustache growth) wirehair, dogs exhibit a breadth of fur structure and type not found in their wild counterparts (Cadieu et al ., 2009 ). When
a genetic screen was conducted across 108 AKC-recognized breeds, seven hair phenotypes were found to segregate with variants of three genes: fibroblast growth factor 5 ( FGF5 ; nucleotide muta-tion), R-spondin-2 ( RSPO2 ; 167 nucleotide insertion), and a keratin ( KRT71 ; nucleotide mutation) (Cadieu et al ., 2009 ). Each permutation of the genetic variants accounted for the vast majority of canine coat texture/patterning. Regarding the evolutionary timing of these fur phenotypes, only
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38 Origins of the dog: Genetic insights into dog domestication
one is considered ancestral (short hair lacking curl, wirehair and furnishings), whereas the other six phenotypes are derived , and have a more recent evolutionary history. The derived variants were
surveyed in the wolf genome and found to be lacking, further reinforcing the view that the canine ancestral fur phenotype is short, straight, smooth and without furnishings (Cadieu et al ., 2009 ).
As with each of the domestic traits discussed, these phenotypes are exclusive to dogs compared to their wild relatives and they likely arose only once (due to the genetic relationships among breeds and the concordance of phenotype with genotype), with humans dispersing those mutations within and across breed lineages through their selective breeding practices. These efforts were the primary driving forces by which the appearance of dog diversity was created despite a paucity of genetic diversity found in their genomes.
# 3.9 Conclusions
The origin of the domestic dog is a complex story, including many unresolved details on location
and timing. The aspects most clearly resolved are the genetic changes linked to the evolving canine
phenotype: the traits that are unique to domestic dogs. Many features of the dog phenotype can now be viewed as an array of genetic variants, each infl uencing the size, shape and function of the ani-mal. As our genetic sequencing technologies decrease in costs, we are better able to search multiple dimensions of the genome for links to what makes a dog a dog. This is an exciting time for canine geneticists who embark on the journey to understand the differences between the dog and wolf genomes, and identify variants linked to behavior and disease, many of which have human analogs.
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