Evolution in dogs. Megan Elmore CS374 11/16/2010. (thanks to Dan Newburger for many slides' content)

Transcription

1 Evolution in dogs Megan Elmore CS374 11/16/2010 (thanks to Dan Newburger for many slides' content)

2 Papers for today Vonholdt BM et al (2010). Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Sutter NB et al (2007). A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs. Anderson TM et al (2009). Molecular and evolutionary history of melanism in North American gray wolves.

3 The dog a population geneticist's best friend Most ancient domesticated animal Intensive and diverse breeding

4 The evolutionary history of dog domestication created two levels of mosaic structure in dog haplotypes. Lindblad-Toh et al. (2005)

5 We study some organisms for physical phenotype...

6 ...and dogs are also cool for cognitive/behavioral phenotypes! Herding Companion Scenthound Retriever Guard Toy Terrier

7 Reconstructing the history of dog domestication

8 The vonholdt data set The authors analyzed 48,000 SNPs in 912 dogs from 85 breeds 225 from 11 populations worldwide 60 Coyotes Primary questions addressed by this paper: Evolutionary relationships among dog breeds Location of origin of the domesticated dog Degree of interbreeding between dog and wolf

9 PCA on all 48K SNPs vonholdt et al., Nature 2010

10 Phylogenetics, quick and dirty (methodological question what is distance, in sequence space/evolutionary time)

11 Haplotype sharing between wolves and dog breeds at windows of 10 SNPs vonholdt et al., Nature 2010

12 Single-allele sharing between wolves and dog breeds

13 Analysis of molecular variance (AMOVA) where in population structure does variance occur? Analogy to Fst Pop A Pop B Are differences between individual dogs attributable to: Variation within breed? 65% Variation within breed grouping? 31% Variation between breed groupings? 3.8%

14 In general, modern dog breeds are closest to Middle Eastern grey wolves.

15 Some interesting regions of recent positive selection in dogs have to do with cognitive traits. Found signals of positive selection using Fst and XP-EHH Most signals found in genic regions Two signals - SNPs involved in memory formation Another example SNP near WBSCR1 Involved in Williams-Beuren syndrome in humans Associated with social traits such as exceptional gregariousness

16 Determining loci associated with quantitative phenotypic traits

17 Dogs vary extensively in size what mutations drive this phenotype? Animal subjects and measurements Cohort of 330 Portuguese Water Dogs Performed PCA on 92 radiographic skeletal measurements Measured short repeat regions throughout dog genome Haseman-Elston Regression portuguese_water_dog2009-med-wide.jpg K. Chase et al., Proc. Natl. Acad. Sci. U.S.A. 2002

18 Identifying quantitative trait loci (QTLs) How to detect association signal eqtl example with SNPs Patient SNP 1 SNP Expressio 2 n 1 A/T G/G T/T C/C T/T G/G A/A C/G T/T G/G 5.6 Large sample size Lots of testcrosses Pedigrees - evidence of haplotype sharing Haseman-Elston regression

19 Pedigrees and Haseman-Elston Pedigree: type of chart used to track inheritance of one or more traits across several generations Identical by Descent (IBD): Two markers are IBD if they are 1) exactly the same and 2) derived from the same ancestral allele

20 Dogs vary extensively in size what mutations drive this phenotype? Animal subjects and measurements Cohort of 330 Portuguese Water Dogs Performed PCA on 92 radiographic skeletal measurements Measured short repeat regions throughout dog genome Haseman-Elston Regression Primary PCA component (overall skeletal size) associated with SNPs near IGF-1 gene Insulin-like growth factor 1 Shown in humans and mice to contribute to body size portuguese_water_dog2009-med-wide.jpg K. Chase et al., Proc. Natl. Acad. Sci. U.S.A. 2002

21 Signs of recent selection near IGF-1 in small dogs

22 Fine-mapping of causative alleles near IGF-1 locus

23 More fine-mapping with Mann-Whitney U test

24 SNP 5 as Candidate for SNP Closest to Causative Mutation Sutter et al., Science 2007

25 Investigating the evolutionary history of a trait in two species

26 Molecular basis for and geographic distribution of coat color in wolves

27 Fine mapping of causative mutations

28 Dating the mutation and finding directionality of dog-wolf haplotype sharing

29 Dating the mutation and finding directionality of dog-wolf haplotype sharing

30 Thanks for listening! References Lindbladh-Toh K et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature Dec 8;438(7069): Vonholdt BM, Pollinger JP, Lohmueller KE, et al. Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature. 2010;464(7290): Sutter NB, Carlos D. Bustamante, et al. A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs. Science. 2007;316(5821): Anderson TM, vonholdt BM, Candille SI, et al. Molecular and evolutionary history of melanism in North American gray wolves. Science (New York, N.Y.). 2009;323(5919):