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Evolution in dogs. CS-374 Abhinay Nagpal abhinay@stanford.edu. Papers that are discussed. Evolution in dogs: A single IGF1 allele is a major determinant of small size in dogs Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication.

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Evolution in dogs

Evolution in dogs

CS-374

Abhinay Nagpal

abhinay@stanford.edu


Papers that are discussed
Papers that are discussed

Evolution in dogs:

  • A single IGF1 allele is a major determinant of small size in dogs

  • Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication


Why are we interested in evolution of dogs
Why are we interested in evolution of dogs?

  • Dogs show greatest variation in size in vertebrates.

  • It has been attributed to domestication

  • Dogs have high similarity of multi locus haplotypes present in wolves in middle east




Identifying qtl
Identifying QTL Dogs

  • Quantitative trait loci (QTLs)-> stretches of DNA linked to the genes that tie to a phentoype trait

  • 2 radiographic skeletal measurements for size and shape-> two QTL (FH2017 at 37.9 Mb and FH2295 at 43.5 Mb) strongly associated with body size


Evolution in dogs
Relationships of skeletal size, SNP markers, IGF1 haplotype, and serum levels of the IGF1 protein in PWDs

A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs


Mixed model for portuguese water dog fine mapping
Mixed model for Portuguese water dog fine-mapping and serum levels of the IGF1 protein in PWDs

  • Y is the vector of the skeletal size trait;

  • α is a vector of fixed effect, the SNP effect we are testing;

  • u is a vector of random effect reflecting the polygenetic background;

  • X and Z are known incidence matrices relating the observations to fixed and random effects, respectively.

  • The variance in the model can be expressed as


Igf1 influences size of dogs
IGF1 Influences Size of dogs and serum levels of the IGF1 protein in PWDs

  • Average heterozygosity in small dogs near IGF1 is only 25% of that in large dogs

  • A narrow precise genomic region holds the variant responsible for small size.


Evidence of association
Evidence of Association and serum levels of the IGF1 protein in PWDs


Fisher s exact test
FISHER’S EXACT TEST and serum levels of the IGF1 protein in PWDs

  • Computes directly the probability of observing a particular set of frequencies in a 2 x 2 table

  • Returns inflated p values


Evolution in dogs

Mann Whitney and serum levels of the IGF1 protein in PWDs

Consider a hare and tortoise race in which the outcomes are as follows:

H H H H H H H H H T T T T T T T T T T H H H H H H H H H H T T T T T T T T T

Median tortoise here comes in at position 19

Median hare comes in at position 20.

However, the value of U (for hares) is 100

Value of U(for tortoises) is 261

http://en.wikipedia.org/wiki/Mann%E2%80%93Whitney_U


Evolution in dogs

Mann Whitney V.S Fisher’s Test and serum levels of the IGF1 protein in PWDs

Cumulative distribution function for Fisher’s exact test and Mann-Whitney U statistic calculated from 83 genomic control SNPs genotyped in small

and giant dogs


Association of body size and frequency of the snp 5 a allele
Association of body size and frequency of the SNP 5 A allele and serum levels of the IGF1 protein in PWDs


Fixation index
Fixation index and serum levels of the IGF1 protein in PWDs

  • Measure of the diversity of randomly chosen alleles within the same sub-population relative to that found in the entire population.


Findings
Findings and serum levels of the IGF1 protein in PWDs

  • IGF1 haplotype substantially contributes to size

  • Size diversity was present early in the history of domestication

  • Ancestral small dog IGF1 haplotype was spread over a large geographic area by trade and human migration



Highlights
Highlights underlying dog domestication

  • The dog is a “striking example” of variation under domestication

  • Evolutionary processes poorly understood

  • Did dogs first evolve in East Asia?


Evolution in dogs
Data underlying dog domestication

  • Survey of 48000 SNPs in dogs and wolves(grey wolf)

  • Typed from 912 dogs - 85 breeds 225 grey wolves

  • 11 globally distributed population


Evolution in dogs

Dog Evolution underlying dog domestication

http://www.sciencemag.org/content/276/5319/1687.full


Bayesian clustering neighbor joining trees
Bayesian clustering & underlying dog domesticationNeighbor joining trees

An example tree with 4 data points.

The clusterings (1 2 3)(4) and (1 2)(3)(4) are tree-consistent partitions

The clustering (1)(2 3)(4) is not a treeconsistent partition

http://www.gatsby.ucl.ac.uk/~heller/bhcnew.pdf


Evolution in dogs

Bayesian Hierarchical Clustering Algorithm underlying dog domestication


Evolution in dogs

Neighbor Joining Trees underlying dog domestication

distance matrix:

http://www.icp.ucl.ac.be/~opperd/private/neighbor.html


Evolution in dogs

We have in total 6 elements (N=6). underlying dog domestication

Step 1: We calculate the net divergence r (i) for each element from all other elements

r(A) = 5+4+7+6+8=30

r(B) = 42

r(C) = 32

r(D) = 38

r(E) = 34

r(F) = 44

Step 2: Now we calculate a new distance matrix using

for each pair

M(ij)=d(ij) - [r(i) + r(j)]/(N-2) or in the case of the pair A,B:

M(AB)=d(AB) -[(r(A) + r(B)]/(N-2) = -13


Evolution in dogs

Step 3: Choose as neighbors pairs for which Mij is the smallest.

==> A and B and D and E.

Let's take A and B as neighbors and we form a new node called U.

Calculate the branch length from the internal node U to A and B.

S(AU) =d(AB) / 2 + [r(A)-r(B)] / 2(N-2) = 1

S(BU) =d(AB) -S(AU) = 4

Step 4: Now we define new distances from U to each other terminal node:

d(CU) = d(AC) + d(BC) - d(AB) / 2 = 3

d(DU) = d(AD) + d(BD) - d(AB) / 2 = 6

d(EU) = d(AE) + d(BE) - d(AB) / 2 = 5

d(FU) = d(AF) + d(BF) - d(AB) / 2 = 7



Evolution in dogs

Analysis of molecular variance (AMOVA) smallest.

Variation within breed : 65% of total variation/diversity

Variation within breed grouping: 31% of total variation/diversity

Variation between breed groupings: 3.8% of total variation/diversity



Evolution in dogs

Observations smallest.

For 5-SNP haplotype windows: haplotype sharing higher

between modern dog breeds and Middle Eastern wolves

For 15-SNP windows : the majority of breeds show the most sharing

with Middle Eastern wolves

This has dog breeds of diverse geographic origins

Only two east Asian breeds (Akita and chow chow) had higher

sharing with Chinese wolves


Evolution in dogs

Findings smallest.

  • Haplotype sharing higher in modern dog breeds and

  • Middle Eastern wolves

  • Eg: basenji, chihuahua, basset hound and borzoi

  • Neighbour-joining trees excellent for breed history & diversity

  • Breed groupings mirror breed classification based on form and function


Evolution in dogs

References smallest.

http://pritch.bsd.uchicago.edu/publications/structure.pdf

http://www.nature.com/nature/journal/v464/n7290/extref/nature08837-s1.pdf

A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs

Sutter et al. Science,2007

Genome-wide SNP and haplotype analyses reveal a rich history underlying

dog domestication. vonHoldt et al. nature,2010.

http://en.wikipedia.org/wiki/Fisher's_exact_test


Evolution in dogs

Backup slide mann whitney smallest.

Consider another hare and tortoise race, with 19 participants of each species

in which the outcomes are as follows:

H H H H H H H H H T T T T T T T T T T H H H H H H H H H H T T T T T T T T T

The median tortoise here comes in at position 19, and thus actually beats the median hare

which comes in at position 20.

However, the value of U (for hares) is 100

(9 Hares beaten by (x) 0 tortoises) + (10 hares beaten by (x) 10 tortoises) = 0 + 100 = 100

Value of U(for tortoises) is 261

(10 tortoises beaten by 9 hares) + (9 tortoises beaten by 19 hares) = 90 + 171 = 261

Consulting tables, or using the approximation below

shows that this U value gives significant evidence that hares tend to do better than tortoises

(p < 0.05, two-tailed).