Course: Advanced Animal Breeding MS program in Animal Production Faculty of Graduate Studies An-najah National University Instructor: Dr. Jihad Abdallah Lecture 1
Some definitions • Gene: the basic physical unit of heredity consisting of a DNA sequence at a specific location on a chromosome. • Locus: the specific location of a gene on a chromosome. • Allele: an alternative form (copy) of the same gene. • Biallelic (or diallelic) gene: If a gene has only two alleles. • Multiallelic gene: If the gene has more than two alleles.
Genotype: the combination of alleles at a single locus or at a number of loci. • Homozygote (homozygous genotype): the alleles carried by the individual at a locus are the same. • Homozygosity: the probability of an individual to be homozygous at a given locus (frequency of homozygotes in the population) • Heterozygote (heterozygous genotype): the alleles carried by the individual at a locus are different. • Heterozygosity: the probability of an individual to be heterozygous at a given locus (frequency of heterozygotes in the population)
Haplotype: a specific combination of alleles at different loci on the same chromosome. • Population: a group of interbreeding individuals living in time and space. It is usually a subdivision of a species. • Phenotype: the visible state of the individual.
1. Additive Gene Action (no dominance) • Each allele has a specific value (average effect) that it contributes to the final phenotype (independent gene effects) • The expression of the heterozygote is exactly midway between the expressions of the homozygous genotypes. J`J` JJ` JJ midpoint Phenotypic expression No allele is dominant over the other
2. Dominance • An interaction between alleles at the same locus such that in heterozygotes one allele has more effect than the other. The allele with the greater effect is dominant over the other allele (called recessive).
Complete dominance: a form of dominance in which the expression of the heterozygote is the same (identical) to the expression of the homozygous dominant genotype. JJ` midpoint J`J` JJ J is dominant over J`
Examples: - Mendel’s Pea plants (the tall allele, T, is completely dominant over the dwarf allele, t) TT tall Tt tall tt dwarf • Presence and absence of horns in cattle (the polled allele is dominant over the horned allele): PP polled Pp polled pp horned
Coat color in cattle (the black color allele is dominant over the red color allele) - BB black - Bb black - bb red • Spider syndrome in sheep: - SS normal lambs - Ss normal lambs - ss crooked legs (have the disease phenotype) The s allele is lethal recessive.
Partial dominance: a form of dominance in which the expression of the heterozygote is intermediate to the expression of the homozygous genotypes but more closely resembles the expression of the homozygous dominant genotype. midpoint J`J` JJ` JJ J is dominant over J` JJ J`J` JJ` midpoint J` is dominant over J
Overdominance: a form of dominance in which the expression of the heterozygote is outside the range defined by the expressions of the homozygous genotypes and most closely resembles the expression of the homozygous dominant genotype. midpoint J`J` JJ JJ` J is dominant over J` JJ` JJ J`J` midpoint J` is dominant over J
3. Epistasis • An interaction among genes at different loci such that the expression of genes at on locus depends on the alleles present at one ore more other loci. • Example: Labrador dogs have three colors (black, chocolate and yellow) determined by genes at two loci: B locus (black color locus) and E locus (extension of pigmentation locus) • B_E_ black (BBEE, BBEe, BbEE, BbEe) • bbE_ chocolate (bbEE, bbEe) • _ _ ee yellow (BBee, Bbee, bbee) - Only yellow dogs breed true (if two yellow dogs are mated, they produce only yellow dogs)
Gene and genotypic frequencies • Gene frequency: the relative frequency of a particular allele in a population. It measures how common the allele is relative to the other alleles on the same locus. • fi = (# of copies of the allele i)/(total # of copies of all alleles) • Genotypic frequency: the relative frequency of a particular genotype in the population. fij= (# of individuals carrying the genotype ij)/ (total # of individuals)
Example: a flock of Andalusian chicken is composed of 36 black (BB), 44 blue (Bb) and 20 white (bb). Compute the gene and genotypic frequencies. • Genotypic frequencies: - Frequency (BB) = P = 36/100 = 0.36 - Frequency (Bb) = H = 44/100= 0.44 - Frequency (bb) = Q = 20/100 = 0.20 • Gene frequencies: • p = frequency (B) = (2x36+44)/(2x100) = 116/200= 0.58 • q = frequency (b) = (44+2x20)/(2x100) = 84/200 = 0.42 • Note that q = 1-p
Factors affecting gene frequencies 1. Systematic forces (the effect is predicted in magnitude and direction): - Migration - Mutation - Selection 2. Random forces (the effect can be predicted in magnitude but not in direction): - Genetic drift (dispersive process)
Migration • Suppose that a large population consists of a proportion m of new immigrants in each generation and the remainder (1-m) being native. • Let the frequency of a certain gene (allele) be qm among the immigrants and q0 among the natives. • The frequency of the gene in the mixed population is: • q1= mqm + (1-m)q0 = m(qm-q0) + q0
Δq = The change of gene frequency caused by one generation of immigration. It is the difference between the frequency before immigration and the frequency after immigration. • Δq = q1-q0 = m(qm-q0) • Thus the rate of change of gene frequency in a population subject to immigration depends on the migration rate and on the difference of gene frequency between immigrants and natives.
Mutation • Mutation: is the process that produces an alteration in DNA or chromosome structure (the source of new alleles). • Two types of mutation: • Non-recurrent mutation: a mutational event that is unique. This type of mutation has very little importance in changing gene frequency in a large population because it has very small chance to survive in the population. • Recurrent mutation: a mutational event that recurs repeatedly. This type of mutation produces a permanent change in gene frequency in a large population.
u v • Mutation rateA1A2 • Initial gene frequenciesp0q0 • New gene frequenciesp0+vq0-up0q0+up0-vq0 • Then the change of gene frequency in one generation is: Δq = up0 – vq0 • At equilibrium Δq = 0, thus at equilibrium pu = qv q = u/(u+v) (note: p = 1-q) • Mutation rates are generally very low (10-5 -10-6)
Selection (Natural selection) • In the previous slides we have supposed that individuals contribute equally to the next generation. • But we must take account of the fact that individuals differ in viability and fertility and thus they contribute different numbers of offspring to the next generation. • The contribution of offspring to the next generation is called the fitness of the individual, the adaptive value or the selective value. • When a gene is subject to selection, its frequency in the offspring is not the same as in the parents because parents with different genotypes pass on their genes unequally to the next generation.
In this way, selection causes changes in gene frequencies and genotypic frequencies. • It is more convenient to think of selection acting against a certain gene in the form of selective elimination of one or more of the genotypes that carry the gene. • The strength of the selection is expressed as the coefficient of selection (s) which is the proportionate reduction in the gametic contribution of a particular genotype compared with the most favored genotype. • The contribution of the favored genotype is 1.0 and the contribution of the genotype selected against is thus (1-s)
Degree of dominance with respect to fitness A2A2 A1A2 A1A1 No dominance (selection against A2) 1-s 1 1-1/2s A2A2 A1A2 A1A1 Partial dominance of A1 (selection against A2 1-s 1-hs 1 A1A1 A1A2 A2A2 Complete dominance of A1 (Selection against A2) 1 1-s A1A1 A2A2 A1A2 Overdominance 1-s1 1-s2 1 Fitness
Selection against a recessive allele Selection is against A2A2 genotype Frequency of A2 before selection is q Frequency of A2 after one generation of selection
Example: calculation of relative fitness and selection coefficients at a single locus. The following are the observed counts from two consecutive generations of Drosophila melanogaster. • What are the relative fitnesses of the three genotypes? • What are the selection coefficients of the three genotypes? • What are the expected genotype frequencies in generation 3? Absolute fitness = (genotype frequency in offspring generation)/(genotype frquency in parent generation)
Solution: Over dominance p = frequency (A1) in G2 = [69+(433/2)]=0.34 q = 0.66
Effectiveness of selection • The effect of selection on changing gene frequency depends on the initial gene frequency (q) and the selection coefficient (s). • Selection is most effective (Δq is large) when q is intermediate but is very ineffective when gene frequency is extreme (q is close to 0 or 1)
How many generations are required to make a certain change in gene frequency? Example: how many generations does it require to reduce the frequency of Albino individuals to half its present value which is 1/20000? Answer: we want to change frequency of Albinos from 1/20000 to 1/40000 1/20000= (q0)2 q0 = 1/141 1/40000 = (qt)2 qt = 1/200 t = 200-141=39 generations (1500 years)
Long-term effects of constant selection • Directional selection: one allele is favored over the other allele increase of the frequency of the favored allele until it becomes fixed in the population ( p = 1.0). • If the selective agent is an environmental factor, directional selection results in adaptation of the population to the environment. • Each generation there are fewer of the maladapted (less fit) genotypes and more of the best adapted (most fit) genotypes. • Directional selection reduces genetic variation leading ultimately to a population monomorphic to the favored allele.
Balancing selection: selection favors the heterozygous genotype. In this case the heterozygote is more fit than either homozygote (heterozygote advantage or overdominance) • Both alleles remain in the population at intermediate frequencies. • At equilibrium (Δq = 0): Frequency of A2: Frequency of A1: s1 is the selection coefficient against A2A2 s2 is the selection coefficient against A1A1
H-W law can be stated as follows: • In an ideal population (large random mating population with no migration, no mutation and no selection) gene frequencies and genotypic frequencies remain stable (constant) from generation to generation and thus genotypic frequencies can be predicted from gene frequencies as follows: • P = p2 • H = 2pq • Q =q2 • In this case the population is said to be in Hardy-Weinberg equilibrium.
Example • A herd of beef cattle of 1000 heads is composed of the following genotypes at a given locus: 300 BB, 400 Bb, and 300 bb. Is the herd in Hardy-Weinberg equilibrium at this locus? p = frequency (B) = (300 (2) + 400)/2000 = 0.5 q = frequency (b) = 1-p = 0.5 The expected numbers: BB p2 (total number) = (0.5)2 (1000) = 250 Bb 2pq (total number) = 2(0.5) (05) (1000) = 500 bb q2 (total number) = (0.5)2 (1000) = 250
To test if the population is in H-W equilibrium we compare the observed numbers with the expected numbers by computing the following test: (Note: 2 1, 0.05 = 3.84) The calculated value is larger than the tabulated value of 3.84. Therefore, we reject the hypothesis that the population is in H-W equilibrium and conclude thatthe population is not in H-W equilibrium.
If the gene frequencies among males and females are different, the population is not in equilibrium. This difference is halved each generation and the population rapidly approaches equilibrium (it takes more than two generations of random mating to reach equilibrium)
Random Genetic Drift • In a large population gene frequencies are stable from generation to generation in absence of migration, mutation and selection. • However, natural populations are typically not large (small and finite). • In small finite populations, gene frequencies are not stable. They are subject to random fluctuations arising from the sampling of gametes (note that the gametes that transmit genes to the next generation are a sample of the genes in the parental population). • Random fluctuations (changes) of gene frequencies from one generation to the next in small populations is called random genetic drift.
Population Subdivision Base population (N = )t0, q0 (in H-W equilibrium) • Sub-populations (lines) • Random mating • No migration • No selection N N N N ….. N N N N ….. N= the number of breeding individuals in each line t = the number of generations since subdivision In any generation, the average of gene frequency across sub-populations is equal to the frequency in the base population The variance of gene frequency after one generation is and after t generations:
Consequences of the dispersive process • Gene frequency within each line changes from one generation to another. Ultimately this leads to fixation of some alleles (frequency is 1.0) and loss of others (frequency becomes 0). The proportion of lines in which a particular allele is fixed is equal to the initial gene frequency of that allele. • Differentiation between lines: random drift within each sub-population leads to genetic differentiation among sub-populations. This differentiation increases as the number of generations increases. • Uniformity within sub-populations: genetic variation within each sub-population is progressively reduced and the individuals become more and more similar in genotypes. • Increased homozygosity: the frequency of homozygotes is increased and the frequency of heterozygotes is reduced within each sub-population.
Frequency in the whole population Genotype A1A1 A1A2 A2A2