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Hello. The topic of this lecture is using of 
molecular genetics in determining the origin

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of dogs and cats. The lecture is part of 
Module 4, Precision Livestock Farming.

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The creation of this presentation was 
supported by the ERASMUS+ KA2 grant

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within the project ISAGREED, Innovation 
of Content and Structure of Study Programs

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in the Field of Animal Genetic and Food 
Resources Management Using Digitalization.

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Plant and animal domestication are rightly 
considered to be the main human cultural

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innovations, ranking in importance 
alongside tool production, fire control,

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or the development of verbal language. Animal 
domestication has interested biologists since

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the time when Charles Darwin first pointed out 
the parallel between evolution through natural

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selection and the breeding of agricultural 
and social animals carried out by humans.

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Molecular genetics can be used to 
determine the origin of dogs and cats.

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After the appearance of the domestic dog 
(Canis familiaris) in archaeological finds,

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the domestication of crops and 
livestock followed soon after,

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allowing humans to significantly expand the food 
they obtained through hunting and gathering.

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As a result, during the Neolithic transition - 
archaeologically documented transition from a

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hunter-gatherer mode of food production to plant 
cultivation and animal husbandry - increasingly

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sophisticated agricultural societies 
developed in many parts of Eurasia,

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northern Africa, and South and Central America.

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The figure shows timelines of the domestication 
of a range of animal species, along with

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corresponding information on key climatic events 
in the last 20,000 years, which likely influenced

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the emergence of agriculture. The domestication 
of dogs was proven to have occurred around

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15,000 years ago, but they accompanied humans 
several thousand years earlier. On the other hand,

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the cat is one of the youngest animal species 
to be domesticated, about 5,000 years ago.

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The origin of dogs has been analyzed using the 
variability of the ASIP gene for coat color.

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Distinctive coat color patterns are 
an integral part of their diversity.

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It is believed that differences in color 
arose through mutations and artificial

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selection during and after domestication from 
wolves, but there are significant gaps in

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understanding how these patterns evolved 
and how they are genetically controlled.

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Specific coat color patterns are caused 
by differential regulation of the Agouti

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(ASIP) gene, which encodes a paracrine 
signaling molecule and antagonist of the

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melanocortin 1 receptor gene (MC1R), which causes 
hair follicle melanocytes to switch from producing

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eumelanin (black or brown pigment) to producing 
pheomelanin (yellow to nearly white pigment).

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The figure shows examples of five patterns 
caused by regulatory deviations of the ASIP gene.

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Dominant yellow (DY), shaded yellow (SY), 
agouti (AG), black saddle (BS), and black (BB).

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The canine ASIP gene has three alternative 
promoters and 5' non-coding exons.

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Structural differences within 1.5-kb 
segments of promoters specific for

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ventral (VP) and hair cycle (HCP) explain the 
five different coat color patterns in dogs.

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Schematically, two VP haplotypes and 
five HCP haplotypes are indicated.

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The star denotes the third promoter and 
non-coding exon not related to the ASIP pattern.

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At the bottom of the figure,

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we can see the five types of coloration 
and combinations of VP and HCP haplotypes.

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Yellow dogs and white wolves share 
an ancient haplotype of ASIP.

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In picture a), genotypes at 377 SNVs 
(columns) at the ASIP locus in gray

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wolves and dogs (rows) are shown, encoded for 
heterozygosity (light blue), homozygosity for

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the reference (yellow) or alternative (dark 
blue) allele, or as missing genotypes (white).

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Alternative first exons (arrows) and nearby 
structural variants associated with DY

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(SINE insertions, green; polynucleotide 
expansions, orange) are included for reference.

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Picture b) shows the phylogeny including 
seven extant canid species and the dog,

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from 48 and 16 kb before and after the 
haplotype of canine pigmentation (HCP),

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respectively. Phylogenetic clusters of the 
gray wolf and dog are emphasized by squares

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indicating relationships consistent (blue) or 
inconsistent (red) with the genome-wide phylogeny.

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In picture d), the phylogeny represents 
the distinct evolutionary history of

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HCP derived from genetic variation in extant 
canids. Structural variants and derived SNVs

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(cyan) differentiate haplotypes of Canids (blue), 
Ghost lineages (red), and basic canids (black).

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The evolutionary origin of ASIP haplotypes 
was examined by constructing phylogenetic

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trees using the maximum likelihood 
method. All dogs and gray wolves form

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a single cluster corresponding to known 
species relationships. However, in the

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HCP tree, dominant yellow and shaded yellow dogs 
form a separate cluster with Arctic gray wolves;

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notably, this cluster is basal to the golden 
jackal and distinct from other canid species.

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Distribution of ASIP alleles in ancient dogs 
and wolves and the evolutionary model for the

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acquisition of dominant yellow color. ASIP 
haplotypes in five ancient dogs (circles),

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two ancient wolves (squares), and 68 modern 
wolves (pie charts) occurring in the Holarctic.

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Picture b) presents a model for the origin 
of the dominant yellow haplotype and its

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transmission to dogs and arctic wolf canids, 
in which molecular changes in modular promoters

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were acquired by introgression (red, HCP1) 
or mutation in gray wolves (blue, VP1).

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Phylogeny of canids for VP (48 kb) and HCP (16 
kb) regions. Derived substitutions shared by

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gray wolves and dogs (blue). Ancestral alleles 
on DY/Arctic wolf haplotypes (red) or BB and

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DY/Arctic wolf haplotypes (orange), corresponding 
to derived substitutions within the canid lineage.

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In picture b), dashed lines delineate the 
HCP region (chr24:23,375,800–23,380,000).

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The solid line denotes the lower boundary 
for phylogenetic analysis. Solid green and

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orange lines indicate the location of 
SINEs and 24-bp insertion associated

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with DY/Arctic wolf haplotype, respectively.
Segments of ASIP haplotypes. Color (red or blue)

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of ASIP haplotype segments indicates ancestral 
origin inferred from phylogenetic analysis.

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Relevant structural variants near ventral (VP) 
and hair cycle (HCP) promoters are shown as yellow

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triangles (polynucleotide expansions), green bars 
(SINE insertions), and white bars (deletions).

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Altered promoter activity is marked 
by a cross (no activity) or additional

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arrow (enhanced expression) based on 
RNA-seq and/or fur color derivation.

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The widespread distribution of 
dominant yellow color in modern

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dog breeds from various locations, as 
well as in the wild domesticated dog,

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the dingo, frequently found in Australia, suggests 
that the dog originated in Southeast Asia.

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Another published study indicates that 
the hypothesis of self-domestication can

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finally be rigorously tested and evaluated 
using high-resolution comparative genomics.

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Origin of cats. Wildcats (Felis silvestris) 
are distributed throughout the Old World.

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DNA analysis suggests that 
cats lived alongside humans for

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thousands of years before they were domesticated.
During that time, their genes changed little from

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those of wild cats, except for one recent change: 
the distinctive tabby markings of domestic cats.

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Surprisingly, wild and domestic cats showed no 
major differences in genetic makeup, and one of

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the few available traits by which they could 
be distinguished was the tabby coat markings.

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The early ancestors of today's domestic 
cats spread from southwest Asia to Europe as

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early as 4400 BCE. Cats likely began to frequent 
agricultural communities in the Fertile Crescent

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about 8000 years ago, where they settled into a 
mutually beneficial relationship as human rodent

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controllers. The second lineage, consisting 
of African cats that dominated in Egypt,

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spread to the Mediterranean and the rest of 
the Old World around 1500 BCE. These Egyptian

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cats likely exhibited behavior that made them 
attractive to humans, such as sociability and

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tameness. Modern genetic analysis of nuclear short 
tandem repeats (STRs) and 16% of the mitochondrial

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DNA (mtDNA) genome in living wild and domestic 
cats has revealed that only one of them,

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the North African/Southwest Asian Felis silvestris 
lybica, has been ultimately domesticated.

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Spatial-temporal distribution of cat maternal 
genealogies. Map a) showing the current

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distribution of the Felis silvestris species 
with the geographic area of each subspecies.

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B) mtDNA tree of the observed lines in 
ancient samples and modern wild and domestic

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cats from literature. C) Spatial-temporal 
representation of ancient cat haplotypes,

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as depicted by symbols from the tree in point b.
Spatial-temporal representation of alleles

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determining the phenotypic variation of tabby 
patterns: mackerel (Ta^M) and spotted (Ta^b).

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We can see that the mackerel pattern is older, 
and the spotted pattern appeared only after

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the turn of the century. The picture shows a 
"cat under a chair" from an ancient Egyptian

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painting with a typical mackerel tabby pattern, 
characteristic for F. silvestris lybica cats.

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The domestication of cats was a complex, long-term 
process with extensive translocations that allowed

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gene flow between geographically separated 
cat populations at different time periods.

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Cats became domesticated companions 
of humans without changing too much.

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Domestic cats look similar to wild 
cats, but they are not solitary

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and can get along with humans and other cats.
This differs from dogs, the first domesticated

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animals. Dogs were selectively bred for specific 
tasks - which never applied to cats - and this

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selection for specific traits led to the 
diversification of dogs into many modern breeds.

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Conclusion: The first high-resolution studies of 
paleogenomes of domesticated animals suggest the

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future of archaeogenetics of domestic animals. 
They aim towards studies with high resolution in

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time and space that will reveal the genetic 
structure of animal domestication and the

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physiological and neurobiological changes 
that occur when domestic and social animals

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come under human control and undergo long-term 
reproductive management and artificial selection.

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It is likely that high-resolution studies of 
pre-domesticated and early animals' paleogenomes

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will provide new important information about 
interesting features of domesticated animals

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and the domestication process.
Thank you for your attention.