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Marcy K. Uyenoyama Department of Biology Duke University Genomic Conflict and DNA Sequence Variation.

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Presentation on theme: "Marcy K. Uyenoyama Department of Biology Duke University Genomic Conflict and DNA Sequence Variation."— Presentation transcript:

1 Marcy K. Uyenoyama Department of Biology Duke University Genomic Conflict and DNA Sequence Variation

2 Population genetics Historically model-rich Present need: model-based interpretation of observed patterns of genomic variation What are hallmarks of each model? Self-incompatibility systems in plants Recognizing genomic conflict due to sexual antagonism Overview

3 Neutral evolution Pure neutrality: distribution of offspring number is independent of any trait in parent Demographic history: deme founding, gene flow Purifying selection: maintain functioning state against random deleterious mutations Selection Balancing selection: maintenance of different forms Selective sweeps: substitution of most fit for less fit Canonical models

4 How do we know it when we see it? Patterns evident in genome variation Model selection Choosing among a small number of canonical models for any particular system Hallmarks of evolution

5 A random sample of genes Ancestral sequence Sample Observed

6 Site frequency spectrum Allele and mutation spectra Multiplicity Number of mutations a = {a 1 = 6, a 3 = 1, a 5 = 1, a 6 = 1}, for a i the number of alleles with multiplicity i

7 After an interval choose a lineage at random –Replace it by two identical copies with probability –Mutate it according to P with probability The neutral coalescent Sample root from stationary distribution of P, mutation transition matrix and bifurcate

8 Events on level k Bifurcation at rateMutation at rate Population parameters: ratios of rates Next event is a bifurcation/coalescence with probability Evolutionary rates

9 Site frequency spectrum Allele and mutation spectra Multiplicity Number of mutations a = {a 1 = 6, a 3 = 1, a 5 = 1, a 6 = 1}, for a i the number of alleles with multiplicity i

10 Mutation Novel allelic types formed at rate u per gene per generation Reproduction Frequency of allele i in the parental population: p i Multinomial sampling of N genes to form the offspring To find: probability of the sample of n genes (n 1, n 2, …, n k ) or (a 1, a 2, …, a n ) fork the number of distinct haplotypes (alleles) n i the number of replicates of allele i a i the number of alleles with i replicates Infinite-alleles model

11 a=(a 1, a 2, …, a n ), for a i the number of alleles represented by i replicates in a sample of size n =2Nu, for N the effective number of genes and u the per-locus, per-generation rate of mutation Ewens (1972, Theoretical Population Biology) Ewens sampling formula

12 Site frequency spectrum Allele and mutation spectra Multiplicity Number of mutations a = {a 1 = 6, a 3 = 1, a 5 = 1, a 6 = 1}, for a i the number of alleles with multiplicity i

13 Population genomics About 750 accessions isolated from natural populations worldwide Summary statistics for sample of 19 entire genomes

14 Arabidopsis SNP spectra Kim et al. (2008 Nature Genetics. 39: 1151) Site frequency spectra differ among functional classes 2 Minor allele counts

15 Biallelic sample of size m Multiplicities i and (m – i ) ESF conditioned on two alleles independent of !

16 a=(a 1, a 2, …, a n ), for a i the number of alleles represented by i replicates in a sample of size n =2Nu, for N the effective number of genes and u the per-locus, per-generation rate of mutation Ewens (1972, Theoretical Population Biology) Ewens sampling formula

17 Actual site frequency spectra Excess of rare and common types, deficiency of intermediate types Data from NIEHS Environmental Genome Project Direct resequencing of loci considered environmentally-sensitive Global representation of ethnicities Hernandez, Williamson, and Bustamante (2007)

18 Black: constant population size Grey: recent expansion from small population size Braverman et al. (1995) Spectrum shape Signature of expansion? Expansions maintain more rare mutations Signature of selective sweep? Neutral variants experience selection as a population bottleneck

19 Arabidopsis SNP spectra Kim et al. (2008 Nature Genetics. 39: 1151) Site frequency spectra differ among functional classes 2 Minor allele counts

20 Modelling a SNP data set Single segregating mutation in the sample genealogy Conditional on exactly one segregating site, determine the distribution of the size (number of descendants) of the branch on which the mutation occurs Exactly two alleles in the sample Conditional on two haplotypes, bearing any number of segregating sites, determine the distribution of numbers of the two alleles Nordborg (2001 Handbook of Statistical Genetics)

21 Two alleles One segregating site Conditioning

22 Single segregating site in a sample of size m Multiplicity i Multiplicity conditioned on a SNP dependent on θ ! Ganapathy and Uyenoyama (2009 Theoretical Population Biology)

23 Arabidopsis SNP spectra Kim et al. (2008 Nature Genetics. 39: 1151) Site frequency spectra differ among functional classes 2 Minor allele counts

24 Population genetics Historically model-rich Present need: model-based interpretation of observed patterns of genomic variation What are hallmarks of each model? Self-incompatibility systems in plants Recognizing genomic conflict due to sexual antagonism Overview

25 Phenotypes Multiple genes generally influence a given phenotype Conflict Target trait value differs among genes that control phenotype Sexual antagonism Male and female function collaborate in reproduction Genes influencing each function may come into conflict Genomic conflict

26 Mating type regions as a battleground S-locus controls self-incompatibility in flowering plants How does sexual antagonism affect the pattern of molecular-level variation within the S-locus? What are hallmarks of conflict? Develop a basis for inference Model-based approach to the analysis of genetic variation Conflict and genomic variation

27 Mariana Ruiz Flower development Basic perfect flower includes both male and female components Fertilization Pollen grains deposited on stigma germinate and pollen tubes grow down style to the ovary

28 Norbert Holstein Mariana Ruiz Gametophytic SI (GSI) Specificity expressed by individual pollen grain or tube determined by own S- allele Pollen rejection Growth of pollen tube arrested in style

29 Norbert Holstein Mariana Ruiz Sporophytic SI (SSI) Specificity expressed by individual pollen grain or tube determined by the S- locus genotype of its parent Pollen rejection Germination of pollen grain may be arrested at stigma surface

30 Norbert Holstein Norbert Holstein Mariana Ruiz AnAn BnBn SnSn Pistil (A) component: rejection of recognized specificities Pollen (B) component: declaration of specificity

31 Mating type regions Uyenoyama (2005)

32 Human Y chromosome Skaletsky et al. (2003 Nature 423: 825) Non-recombining male-specific Y (MSY) Euchromatic region ~ 23 MB Differences between two random Ys every 3 – 4 KB Mammalian sex determinant SRY Y-linked regulator of transcription of many male-specific Y-linked genes

33 Mating type regions Uyenoyama (2005) Linkage between pistil (A) and pollen (B) components is essential to SI function Pollen: declaration of specificity Pistil: rejection of recognized specificities

34 Brassica S-locus Pollen component Pistil component Nasrallah (2000 Curr. Opin. Plant Biol.) Natural populations often contain 30 – 50 S-alleles

35 Vierstra (2009, Nature Reviews Molecular Cell Biology) Ubiquitin tags proteins for degradation Style: S-RNase disrupts pollen tube growth Upon entering a pollen tube, S-RNases initially sequestered in a vacuole In incompatible crosses, vacuole breaks down, releasing S-RNases into cytoplasm of pollen tube Pollen: SLF (S-locus F-box) Mediator of ubiquitinylation (attachment of ubiquitin) Disables all S-RNases except those of the same specificity

36 Pistil: why reject fertilization? Screening of potential mates may improve offspring quality Cost under incomplete reproductive compensation: ovules may go unfertilized Pollen: why provoke rejection? Self-rejection may improve quality of own ovules Rejection by other plants reduces siring success Hide behind another S-specificity in sporophytic SI? Decline to declare S-specificity altogether? Sexual antagonism

37 Basic discrete time recursion Symmetries in genotype and allele frequencies Model change in frequency of focal allele i, assuming all other alleles in equal frequency GSI model Wright (1937, Genetics)

38 Change in allele frequency Diffusion equation coefficients holds for large population size (N) and u (rate of mutation to new S-alleles) of order 1/N Diffusion approximation Wright (1937, Genetics)

39 Number of S-alleles Frequency in population Diffusion with jumps Turnover rate Wrights diffusion model

40 Takahata (1993, Mechanisms of Molecular Evolution) Expansion of time scale under balancing selection High rate of invasion of rare alleles Promotes invasion of new and retention of rare types Maintains high numbers of alleles Genealogical relationships Tree shape similar under symmetric balancing selection and neutrality Greatly expanded time scale

41 Quasi-equilibrium of S-alleles Invasion of new, rare S-alleles balanced by extinction of common S-alleles Expansion of time scale Rate of divergence among S-allele classes similar to rate among neutral lineages, but in a population of size fN: S-allele turnover

42 Basic discrete time recursion Diffusion approximation Parameters: Effective population size (N) Rate of mutation to new S-specificities (u) Gametophytic SI models

43 Stationary distribution of allele frequency Most time spent close to deterministic equilibrium (1/n) or in boundary layer close to extinction Number of S-alleles Analytical expectation for number of common S-alleles Simulation results Vallejo-Marín and Uyenoyama (2008)

44 Norbert Holstein Norbert Holstein Mariana Ruiz AnAn BnBn SnSn Pistil (A) component: rejection of recognized specificities Pollen (B) component: declaration of specificity

45 Pollen specificity in GSI Each pollen expresses its own specificity Rarer specificities are incompatible with fewer plants Incompatible matings For n S-alleles in equal frequencies, a pollen type is incompatible with a proportion 2/n of all plants Norbert Holstein

46 Pistil: why reject fertilization? Screening of potential mates may improve offspring quality Cost under incomplete reproductive compensation: ovules may go unfertilized Pollen: why provoke rejection? Self-rejection may improve quality of own ovules Rejection by other plants reduces siring success Hide behind another S-specificity in sporophytic SI? Decline to declare S-specificity altogether? Sexual antagonism

47 Self-pollen fraction (s) Relative viability of inbred offspring ( ) Full SC Polymorphism Full SI Fate of style-part mutant A n+1 BnBn SaSa

48 Self-pollen fraction (s) Relative viability of inbred offspring ( ) Full SC Polymorphism Full SI Disruption Uyenoyama, Zhang, and Newbigin (2001) Fate of pollen-part mutant AnAn B n+1 SbSb

49 A n+1 BnBn SaSa AnAn B n+1 SbSb A n+1 B n+1 S n+1 AnAn BnBn SnSn Direction of pollen flow Uyenoyama, Zhang, and Newbigin (2001)

50 A n+1 BnBn SaSa AnAn B n+1 SbSb A n+1 B n+1 S n+1 AnAn BnBn SnSn Uyenoyama, Zhang, and Newbigin (2001) Evolutionarily unlikely TURN OFF Partial breakdown of SI by pollen disablement TURN ON Restoration of SI by stylar recognition Evolutionarily unlikely

51 Joint genealogies Newbigin, Paape, and Kohn (2008) Unlike S-RNase genes, SLF genes show –Low divergence between allelic types –No trans-specific sharing of lineages Solanaceae and PlantaginaceaeRosaceae

52 Family-specific genealogies Rosaceae: do highly-diverged, ancient SFB lineages reflect continuous operation or restoration of same F-box genes? Solanaceae, Plantaginaceae: Recruitment of new F- box genes? Turnover of pollen-specificity loci Expression and recognition of a paralogue of the former pollen specificity gene? Can homologues be distinguished from paralogues with new function? Cycles of loss/restoration of SI?

53 Brassica S-locus Pollen component Pistil component Nasrallah (2000 Curr. Opin. Plant Biol.) Natural populations often contain 30 – 50 S-alleles

54 Sexual antagonism in mating type regions Neutral variation in linked regions Rates of substitution at determinants of mating type Inference Goal: use the pattern of variation in population samples of genomic regions as a basis for inference about the evolutionary process Detection genomic conflict and other forms of selection mating systems and population structure An appeal for inference methods

55 Norbert Holstein Pollen specificity in SSI Codominance Both specificities expressed Almost twice as many incompatible styles under SSI than GSI for same number of S-alleles Complete dominance One specificity expressed

56 SRK genealogies Edh, Widén and Ceplitis (2009) Sporophytic SI Diploid genotype of pollen parent determines S-specificity of each pollen grain Class I is dominant over Class II, with codominance within class Class II: pollen-recessive Lower number of segregating alleles, each with relatively higher frequency in population Greater genealogical relationship within class?

57 Is class II younger than class I? Uyenoyama (1995) MRCA ages Class I: 25.5 ± 8.1 MY Class II: 3.1 ± 0.9 MY I/II: 41.4 ± 12.7 MY Origin of SLG/SRK system 42.1 ± 9.0 MY


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