1. Lecture 6: Inbreeding September 10, 2012

2. Announcements Hari’s New Office Hours  Tues 5-6 pm  Wed 3-4 pm  Fri 2-3 pm In computer lab 3306 LSB

3. Last Time uMore Hardy-Weinberg Calculations  Merle Patterning in Dogs: Excel sheet posted uFirst Violation of Hardy-Weinberg assumptions: Random Mating uEffects of Inbreeding on allele frequencies, genotype frequencies, and heterozygosity

4. Important Points about Inbreeding uInbreeding affects ALL LOCI in genome uInbreeding results in a REDUCTION OF HETEROZYGOSITY in the population uInbreeding BY ITSELF changes only genotype frequencies, NOT ALLELE FREQUENCIES and therefore has NO EFFECT on overall genetic diversity within populations uInbreeding equilibrium occurs when there is a balance between the creation (through outcrossing) and loss of heterozygotes in each generation

5. Today uSelf-fertilization and mixed mating systems uInbreeding equilibrium uEstimating inbreeding coefficients from pedigrees uRelatedness and kinship

6. Extreme Inbreeding: Self Fertilization uCommon mode of reproduction in plants: mate only with self uAssume selfing newly established in a population u½ of heterozygotes become homozygotes each generation uHomozygotes are NEVER converted to heterozygotes

7. Self Fertilization AA aa Aa A a aA Aa Self-Fertilizations AA A A AA AA Self-Fertilizations ½ Aa each generation ½ AA or aa (allele fixed within lineage) http://www.life.illinois.edu/ib/335/BreedingSystems/BreedingSystems.html

8. Decline of Heterozygosity with Self Fertilization uSteady and rapid decline of heterozygosity to zero AA or aa Aa

9. Partial Self Fertilization uMixed mating system: some progeny produced by selfing, others by outcrossing (assumed random) uRate of outcrossing = T uRate of selfing = S uT+S=1 uHeterozygosity declines to equilibrium point aa AA Aa

10. What determines the equilibrium frequency of heterozygotes in a population with mixed selfing and outcrossing?

11. Inbreeding Equilibrium uProduction of heterozygotes by outcrossing balances loss of heterozygotes by selfing uFor any value of p and S, there is a characteristic equilibrium point, regardless of starting genotype frequencies uInbreeding coefficient also reaches equilibrium point, purely a function of selfing rate D eq H eq R eq See lab notes for derivations Outcross Combinations That Produce Heterozygotes AA x aa AA x Aa aa x Aa Aa x Aa gain loss

12. Estimating Selfing in Populations Level of selfing can be readily estimated from allele frequencies and observed heterozygosity: What are the assumptions of this calculation?

13. Estimating Inbreeding from Pedigrees uMost accurate estimate of f derived from direct assessment of relationships among ancestors Half First-Cousins

14. Estimating Inbreeding from Pedigrees uProbability P contains two A 1 alleles IBD uOverall: uThere are two alleles in the common ancestor, so there are two possibilities to inherit different alleles IBD uProbability P contains any alleles IBD is therefore:

15. Chain Counting uCount links to Common Ancestor starting with one parent of inbred individual and continuing down to other parent  D-B-CA-C-E  N=5 links For multiple common ancestors, m: If common ancestors are inbred as well: Where f CAi is inbreeding coefficient of common ancestor i

16. Kinship Coefficient CA 2 CA 1 D B C E uEstimate of relationship between two individuals in a population, D and E uProbability a randomly selected allele from each is Identical by Descent uEasiest to estimate as f of hypothetical progeny, p P

17. Relatedness uSewall Wright revolutionized study of inbreeding in 1922 uDefined coefficient of relationship (r)  Shared alleles between related individuals result in genetic correlation  Also the fraction of alleles that two individuals share IBD uCan be estimated as twice the inbreeding coefficient of possible offspring (i.e., twice the kinship) http://www.harvardsquarelibra ry.org/unitarians/wright- sewall.html

18. Relatedness uRelatedness is twice the probability that two alleles, one chosen randomly from each individual, are IBD r=0.5 for parent–offspring and full sibs r=0.25 for half-sibs, and r=0.125 for first cousins. uCan be estimated from sharing of alleles conditioned on allele frequencies

19. Estimating Relatedness Without a Pedigree uMolecular markers provide indication of relatedness of individuals based on shared alleles uMore polymorphic markers are preferable: microsatellites Source: SilkSatDB Allozymes Microsatellites Lowe, Harris, and Ashton 2004

20. Estimating Relatedness Without a Pedigree uIn many cases, relationships among samples are unknown uRelationships can be estimated using multiple, highly polymorphic loci uQueller and Goodnight (1999, Mol Ecol. 8:1231) developed a program, KINSHIP, that estimates relatedness based on likelihood ratios (explained in more detail later) Number of Microsatellites Required to Distinguish Relationships

21. Relatedness in Natural Populations uWhite-toothed shrew inbreeding (Crocidura russula) (Duarte et al. 2003, Evol. 57:638-645) uBreeding pairs defend territory uSome female offspring disperse away from parents uHow much inbreeding occurs? u12 microsatellite loci used to calculate relatedness in population and determine parentage u17% of matings from inbreeding Number of matings Relatedness Parental Relatedness Offspring Heterozygosity

22. Inbreeding and allele frequency uInbreeding alone does not alter allele frequencies uYet in real populations, frequencies DO change when inbreeding occurs uWhat causes allele frequency change? uWhy do so many adaptations exist to avoid inbreeding?

24. Natural Selection uNon-random and differential reproduction of genotypes  Preserve favorable variants  Exclude nonfavorable variants uPrimary driving force behind adaptive evolution of quantitative traits

25. Fitness uVery specific meaning in evolutionary biology:  Relative competitive ability of a given genotype uUsually quantified as the average number of surviving progeny of one genotype compared to a competing genotype, or the relative contribution of one genotype to the next generation uHeritable variation is the primary focus uExtremely difficult to measure in practice. Often look at fitness components uConsider only survival, assume fecundity is equal