Today: Multiple loci (continued) Inbreeding & pedigree analysis Discuss outlines

Gametic disequilibrium: When should we be concerned about possible nonrandom associations between loci? (1) Closely linked markers. (2) Small effective population size (3) Hybridization

(1) Closely linked markers. 5 microsatellite loci Soya sheep MHC Sheep chromosome 20

(2) Small effective population size Guest Box 10: Phillip Island foxes

Yellowstone cutthroat trout (3) Hybridization Westslope cutthroat trout (WCT) Oncorhynchus clarki lewisi Yellowstone cutthroat trout (YCT) O. c. bouvieri Rainbow trout (RT) O. mykiss

D = coefficient of gametic disequilibrium (measure of nonrandom association of two loci)

Genotypes at eight diagnostic allozyme loci and mtDNA from Forest Lake, Montana. W = homozygous WCT WY = heterozygous Y = homozygous YCT

Hybrid swarm: a population of individuals that all are hybrids by varying numbers of generations of backcrossing with parental types and mating among hybrids.

Decay of gametic disequilibrium

Which of these two hybrid swarms is older? Note: A, B, and C are linked pairs of loci.

Bull trout = BL (L= homozygous) Brook trout = BR (R = homozygous)

Chapter 13 Inbreeding (Fred) What is inbreeding? How can we estimate F? Pedigree analysis Gene drop analysis Molecular markers Inbreeding Depression (Marty) What are the causes of inbreeding depression? How do we measure inbreeding depression?

Inbreeding: the mating between individuals that are more related than the average relatedness among all pairs of individuals. Inbreeding depression: reduction in fitness of inbred individuals.

Inbreeding depression Reduced survival of progeny from selfing compared to outcrossing in monkey flowers. Inbreeding depression

. . the bad sex is better than no sex at all hypothesis. (2002) The reproductive assurance hypothesis explains how self-fertilization can be advantageous in species with strong inbreeding depression. Self-fertilization is beneficial if it enables the production of seeds when pollinators and/or potential mates are scarce. If opportunities for outcrossing are limited, selfing can be selected even if inbreeding depression is strong. Although the reproductive assurance hypothesis, first championed by Darwin, is now widely accepted as an explanation for the evolution of selfing, it has never been subject to a rigorous experimental test. . . the bad sex is better than no sex at all hypothesis.

Journal of Evolutionary Biology 20:1531. 2007.

F = 0.25

“Inbreeding: one word, many meanings” genetic drift (FST; see section 9.1). (2) non-random mating within local populations (FIS; see section 9.1). (3) the increase in genome wide homozygosity (measured by pedigree F) caused by matings between related individuals

Large: ponderosa pine in the northern Rockies FIS ~ 0.10 Inbreeding can occur in both large and small populations. Large: ponderosa pine in the northern Rockies FIS ~ 0.10

“Inbreeding: one word, many meanings” genetic drift (FST; see section 9.1). (2) non-random mating within local populations (FIS; see section 9.1). (3) the increase in genome wide homozygosity (measured by pedigree F) caused by matings between related individuals

Guam rail

IBD Identical in state not IBD Not identical in state

We are all “inbred”! An individual is inbred if its mother and father share a common ancestor. However, any two individuals in a population are related if we trace their ancestries back far enough. How many ancestors did you have 1,000 years ago? G = 25 1,000/25 = 40 generations 240 = 1,100,000,000,000 = 1,100 billion

Growth of human population

Pedigree analysis An individual is inbred if its mother and father share a common ancestor. However, any two individuals in a population are related if we trace their ancestries back far enough. We must therefore define inbreeding relative to some "base" population in which we assume all individuals are unrelated to one another. We usually define the base population operationally as those individuals in a pedigree beyond which no further information is available (i.e., founders).

Individual H is homozygous (and IBD) for the 1 allele that was present in his grandmother (A) who is a common ancestor of both his mother (D) and father (E).

"Inbred" individuals will have increased homozygosity (and decreased heterozygosity) over their entire genome. The pedigree inbreeding coefficient (F) is the expected increase in homozygosity for inbred individuals; it is also the expected decrease in heterozygosity throughout the genome. F ranges from 0 (for non-inbred individuals) to 1 (for totally inbred individuals).

How can we estimate F? Pedigree analysis Gene drop analysis Molecular markers

What is F of individual X? What is the probability that X is homozygous for an allele present in A, the common ancestor of his both mother and father?

Path analysis: focus only on common ancestor (disregard B & C)

A3A4 A1A2 A5A6 We assume that each “founder” is heterozygous for two unique alleles.

A3A4 A1A2 A5A6 What is the probability that X is homozygous (A1A1 or A2A2 ) for an allele present in A, the common ancestor of his both mother and father?

A3A4 A1A2 A5A6 A1 A1 A1 A1 A1A1 What is the probability that X is A1A1? (1/2)4 = 1/16 = 0.0625

A3A4 A1A2 A5A6 A2 A2 A2 A2 A2A2 What is the probability that X is A2A2? (1/2)4 = 1/16 = 0.0625

A3A4 A1A2 A5A6 What is the probability that X is A1A1 or A2A2? Sum rule: 0.0625 + 0.0625 = 0.1250

Trace path that connects X’s parents

F = (1/2)N(1 + FCA) DAE X has three individuals in his loop A is common ancestor F = (1/2)N(1 + FCA) N = # individuals in loop FCA = F of common ancestor =FA FX = (1/2)3 = 0.125

Redraw this pedigree as a path diagram and calculate the inbreeding coefficients of individual G.

F = (1/2)N(1 + FCA)

What about multiple levels of common ancestry? F = (1/2)N(1 + FCA) FG = (1/2)3 (1+FB)= 0.125 FK = (1/2)3(1+FG) FK = (0.125)(1+0.125) = 0.141

Pedigree analysis in the wild Pedigrees can also be constructed in wild populations using a combination of observations and molecular analysis.

Guest Box 13

How can we estimate F? Pedigree analysis Gene drop analysis Molecular markers

“Gene drop analysis” Assign unique alleles to each “founder” 5 1 2 4 “Drop” the alleles through the pedigree by simulating Mendelian segregation. 1 5 This can be used to find more than just the inbreeding coefficient. How much allelic diversity is expected to be lost?

50% loss of heterozygosity and alleles in living animals Do this 10,000 times and than use the means.

Assume that individuals F1-F4 above are the founders of a captive breeding program. Use coin-flips to derive one possible outcome of a gene-drop analysis for this pedigree. What are the observed heterozygosities for individuals A-D based upon the outcome of your single gene-drop? How many of the eight original alleles remain in the captive population based upon your single gene drop outcome?   If you performed 10,000 such gene drops, what do you think the average observed heterozygosity would be for individuals A-D?

xx xx xx xx xx xx xx xx xx

How can we estimate F? Pedigree analysis Gene drop analysis Molecular markers

Captive population of wolves

Pedigree F correlated with heterozygosity (H) at 29 microsatellite loci observed predicted (F)

Wild animals Inbred (F > 0.13, in this case) Non-inbred

The outline of your paper should include the title, primary and secondary section headings, and a brief description of each section. The more detailed your outline is, the more helpful I can be in making my comments. Section: Scientific papers are generally divided into discrete sections and subsections that both help the reader follow the writer's presentation and help the writer organize the paper. Make sure that you include sections and subsections in organizing your paper The first section of the main body of your paper should be an Introduction. The first part of this section should introduce your topic and tell the reader why this is an interesting and important topic. You should include a statement of the purpose and objectives of your paper at the end of your Introduction. Include 20 or so relevant citations at the end of your outline. Remember to use the Literature Cited format for the journal Conservation Biology.

Remember to use the Literature Cited format for the journal Conservation Biology. You should start and maintain your own computer bibliographic database. Barry Brown: RefWorks rather than EndNote Web.