1. Lecture 7: Inbreeding and Crossbreeding

2. Inbreeding Inbreeding = mating of related individuals Often results in a change in the mean of a trait Inbreeding is intentionally practiced to: –create genetic uniformity of laboratory stocks –produce stocks for crossing (animal and plant breeding) Inbreeding is unintentionally generated: –by keeping small populations (such as is found at zoos) –during selection

3. Genotype frequencies under inbreeding The inbreeding coefficient, F F = Prob(the two alleles within an individual are IBD) -- identical by descent Hence, with probability F both alleles in an individual are identical, and hence a homozygote With probability 1-F, the alleles are combined at random

4. GenotypeAlleles IBDAlleles not IBDfrequency A1A1A1A1 Fp(1-F)p 2 p 2 + Fpq A2A1A2A1 0(1-F)2pq A2A2A2A2 Fq(1-F)q 2 q 2 + Fpq Alleles IBD Random mating

5. Changes in the mean under inbreeding  F =  0 - 2Fpqd Using the genotypic frequencies under inbreeding, the population mean  F under a level of inbreeding F is related to the mean  0 under random mating by GenotypesA 1 A 1 A 1 A 2 A 2 A 2 0 a+d 2a freq(A 1 ) = p, freq(A 2 ) = q

6. For k loci, the change in mean is Here B is the reduction in mean under complete inbreeding (F=1), where There will be a change of mean value dominance is present (d not zero) For a single locus, if d > 0, inbreeding will decrease the mean value of the trait. If d < 0, inbreeding will increase the mean For multiple loci, a decrease (inbreeding depression) requires directional dominance --- dominance effects d i tending to be positive. The magnitude of the change of mean on inbreeding depends on gene frequency, and is greatest when p = q = 0.5

7. Break for Problem 1

8. Inbreeding Depression and Fitness traits InbredOutbred

9. Define ID = 1-  F /  0 = 1-(  0 -B)/  0 = B/  0 Drosophila TraitLab-measured ID = B/  0 Viability0.442 (0.66, 0.57, 0.48, 0.44, 0.06) Female fertility0.417 (0.81, 0.35, 0.18) Female reproductive rate0.603 (0.96, 0.57, 0.56, 0.32) Male mating ability0.773 (0.92, 0.76, 0.52) Competitive ability0.905 (0.97, 0.84) Male fertility0.11 (0.22, 0) Male longevity0.18 Male weight0.085 (0.1, 0.07) Female weight-0.10 Abdominal bristles0.077 (0.06, 0.05, 0 ) Sternopleural bristles-.005 (-0.001, 0) Wing length0.02 (0.03, 0.01) Thorax length0.02

10. Why do traits associated with fitness show inbreeding depression? Two competing hypotheses: – Overdominance Hypothesis : Genetic variance for fitness is caused by loci at which heterozygotes are more fit than both homozygotes. Inbreeding decreases the frequency of heterozygotes, increases the frequency of homozygotes, so fitness is reduced. – Dominance Hypothesis: Genetic variance for fitness is caused by rare deleterious alleles that are recessive or partly recessive; such alleles persist in populations because of recurrent mutation. Most copies of deleterious alleles in the base population are in heterozygotes. Inbreeding increases the frequency of homozygotes for deleterious alleles, so fitness is reduced.

11. Estimating B In many cases, lines cannot be completely inbred due to either time constraints and/or because in many species lines near complete inbreeding are nonviable In such cases, estimate B from the regression of  F on F,  F =  0 - BF 0 00 1  0 - B If epistasis is present, this regression is non-linear, with C k F k for k-th order epistasis FF F

12. Minimizing the Rate of Inbreeding Avoid mating of relatives Maximum effective population size N e Ne maximized with equal representation –Contribution (number of sibs) from each parent as equal as possible –Sex ratio as close to 1:1 as possible –When sex ratio skewed (r dams/sires ), every male should contribute (exactly) one son and r daughters, while every female should leave one daughter and also with probability 1/r contribute a son

13. Variance Changes Under Inbreeding F = 0F = 1/4F = 3/4F = 1 Inbreeding reduces variation within each population Inbreeding increases the variation between populations (i.e., variation in the means of the populations)

14. Variance Changes Under Inbreeding GeneralF = 1F = 0 Between lines 2FV A 2V A 0 Within Lines (1-F) V A 0VAVA Total (1+F) V A 2V A VAVA

15. Line Crosses: Heterosis When inbred lines are crossed, the progeny show an increase in mean for characters that previously suffered a reduction from inbreeding. This increase in the mean over the average value of the parents is called hybrid vigor or heterosis A cross is said to show heterosis if H > 0, so that the F 1 mean is average than the average of both parents.

16. Expected levels of heterosis If p i denotes the frequency of Q i in line 1, let p i +  i denote the frequency of Q i in line 2. The expected amount of heterosis becomes Heterosis depends on dominance : d = 0 = no inbreeding depression and no. heterosis as with inbreeding depression, directional dominance is required for heterosis. H is proportional to the square of the difference in gene frequency Between populations. H is greatest when alleles are fixed in one population and lost in the other (so that |  i | = 1). H = 0 if  = 0. H is specific to each particular cross. H must be determined empirically, since we do not know the relevant loci nor their gene frequencies.

17. Heterosis declines in the F 2 In the F 1, all offspring are heterozygotes. In the F 2, Random mating has occurred, reducing the frequency of heterozygotes. As a result, there is a reduction of the amount of heterosis in the F 2 relative to the F 1, Since random mating occurs in the F 2 and subsequent generations, the level of heterosis stays at the F 2 level.

18. Agricultural importance of heterosis Crop% planted as hybrids % yield advantage Annual added yield: % Annual added yield: tons Annual land savings Maize65151055 x 10 6 13 x 10 6 ha Sorghum48401913 x 10 6 9 x 10 6 ha Sunflower6050307 x 10 6 6 x 10 6 ha Rice1230415 x 10 6 6 x 10 6 ha Crosses often show high-parent heterosis, wherein the F 1 not only beats the average of the two parents (mid-parent heterosis), it exceeds the best parent.

19. Break for Problem 2

20. Crossbreeding in Animals Individual heterosis: Enhanced performance in a hybrid individual Maternal heterosis: Enhanced maternal performance, e.g., increased litter size and higher survival rates of offspring Maternal heterosis is often comparable, and can be greater than, individual heterosis

21. hIhI nhMhM n Birth weight 3.2%425.1%12 Weaning weight 5.0%566.3%27 Preweaning growth rate 5.3%19 Postweaning growth rate 6.6%10 Yearling weight 5.2%18 Ovulation rate -2.0%4 Fertility 2.6%208.7%30 Prolificacy 2.8%203.2%31 Birth-weaning survival 9.8%292.7%25 Lambs per ewe 5.3%2011.5%25 Lambs reared per ewe 15.2%2014.7%25 Total weight lambs/ewe 17.8%2418.0%25 Carcass traits 0%725

22. Maternal and individual heterosis effects can be combined by using crossbred (hybrid) dams. For example, for total weight of lambs rear per mated ewe has an 18% individual heterotic advantage in a crossbred offspring and an addition 18% advantage (from maternal heterosis) when crossbred ewes are used in place of purebred ewes. This combining of maternal and individual heterotic effects is one reason why three-way crosses are common in animal breeding, generally by crossing a male from line A with a hybrid female (from a B x C cross). This strategy exploits maternal heterosis in the female, with the sire line often chosen for its contribution to some production trait.

23. Synthetics and Rotational Crossbreeding To maximally exploit heterosis, we ideally would use only F 1 individuals, as the heterotic advantage decreases in the F 2 Problem: In (most) large farm animals, the number of offspring is on order of the number of dams. Thus, to produce n triple cross hybrid offspring requires on the order of 2n dams (the granddam to produce the B x C dam, and the dam herself in the A X (B X C) cross).

24. One partial solution around this problem: Synthetics: n parental lines are chosen and a random-mating population formed by first making all n(n-1)/2 pairwise intercrosses between the lines () Average of the founding lines Mean of the F1 from all pairwise crosses The larger n (number of founding lines), smaller decrease in H This is equivalent to

25. Second Solution: Rotational Crossbreeding A x B ( A x B) x A dam cross dam back to A sire cross dam back to B sire (( A x B) x A) x B dam cross dam back to A sire And so on ….

26. The expected mean value under a two-way rotation: The expected mean value under a three-way rotation: Key: Heterosis advantage divided by 3, not by 2 as in F 2 Under a 4-way rotation, the order matters: 1/7th of heterosis is lost 1/15 of heterosis is lost Mean of all six pair-wise crosses Mean of crosses of nonadjacent lines

27. Trait PF1F1 RSBC Weaning weight154.2180.5178.3170.1181.4 12-month weight210.5246.8232.2212.3233.6 18-month weight274.9315.7296.6276.6295.3 12-18 m weight gain64.468.964.464.661.7 Note that F 1 > R > S > P For a 2-way rotation: For the 2-breed synthetic, For weaning weight

28. Break for Problem 3

29. Estimating the Amount of Heterosis in Maternal Effects Contributions to mean value of line A Individual genetic effect (BV)Maternal genetic effect (BV)Grandmaternal genetic effect (BV)

30. Consider the offspring of an A sire and a B dam Individual genetic value is the average of both parental lines Maternal and grandmaternal effects from the B mothers Contribution from (individual) heterosis Now consider the offspring of an B sire and a A dam Individual genetic and heterotic effects as in A x B cross Maternal and grandmaternal genetic effects for B line

31. Hence, an estimate of individual heteroic effects is (()) Likewise, an estimate of maternal/grandmaternal effects is given by How about estimation of maternal heteroic effects?

32. . The mean of offspring from a sire in line C crossed to a dam from a A X B cross (B = granddam, AB = dam) Average individual genetic value (average of the line BV’s) New individual heterosis of C x AB cross Genetic maternal effect (average of maternal BV for both lines) Grandmaternal genetic effect Maternal genetic heteroic effect “Recombinational loss” --- decay of the F 1 heterosis in The F 2 One estimate (confounded) of maternal heterosis