Quantitative Genetics of Natural Variation: some questions Do most adaptations involve the fixation of major genes? micromutationist view: adaptations arise by allelic substitution of slight effect at many (innumerable) loci, and no single substitution constitutes a major portion of an adaptation (Darwin, Fisher) macromutationist views: 1. single “systemic” mutations produce complex adaptations in essentially perfect form (Goldschmidt) 2. adaptation often involves one or a few alleles having large effects Of 8 studies, only 3 consistent with changes involving > 5 loci (Orr and Coyne 1992)

Quantitative Genetics of Natural Variation: some questions How many loci contribute to naturally occurring phenotypic variation, and what are the magnitudes of their effects? What sorts of genes —and changes in these genes—are responsible for trait variation within populations (e.g., transcription factors, structural genes, metabolic genes) Do the same genes that contribute to variation within species also contribute to variation between species? What genes underlie evolutionary novelties? What are the genetic bases for evolutionary novelties? How do pleiotropic effects of genes evolve? Answers require a mechanistic approach towards identifying the relevant loci and how genetic differences are translated into phenotypic differences

Quantitative traits depend on multiple underlying loci one locus one locus + environment two loci + environment four loci + environment many loci + environment

– ad+ a genotypic value 0 A2A2A2A2 A1A2A1A2 A1A1A1A1 genotype Phenotypic Value and Population Means (Falconer and Mackay Ch. 7) Phenotypic value = Genotypic value + Environmental Deviation P = G + E GenotypeFreq Value Freq x Val A 1 A 1 p 2 +a p 2 a A 1 A 2 2pq d 2pqd A 2 A 2 q 2 -a -q 2 a Sum = Pop Mean = a(p-q) + 2dpq

Predictable Larval Habitat Predictable Ephemeral Pond Time HatchingMetamorphosis Timing of Metamorphosis The majority of organisms on planet earth have complex life cycles

T3 Hypothalamus TRH TSH TRs transcription Target cells TH Pituitary Thyroid T4 deiodionation Thyroid Hormone Receptors as Candidate Genes for Variation in Metamorphic Timing An extreme difference in metamorphic timing

Thyroid Hormone Receptor Alpha Genotype Timing of Metamorphosis (Days) A1A1 A1A2A2A a -a d 0 Homozygote Midpoint (175) Thyroid Hormone Receptors : A Hypothetical Example

p = f(A1)q = f(A2) A1A1A1A2A2A2 GenotypeFreq Value Freq x Val A 1 A 1 p 2 25 p 2 (25) A 1 A 2 2pq -15 2pq(-15) A 2 A 2 q q 2 (25) Sum = Pop Mean = 25(p-q) + 2(-15)pq Mean -25 (150) (158.7) -7.5 (167.5) 3.7 (178.7) 25 (200) (reduces time)(adds time)

Let’s Consider a Second Locus Thyroid Hormone Receptor Alpha Genotype Timing of Metamorphosis (Days) A1A1 A1A2A2A a -a 0 Homozygote Midpoint (170) A1A1 A1A2 A2A Thyroid Hormone Receptor Beta Genotype Timing of Metamorphosis (Days) 0

P = f(A1)Q = f(A2) A1A1A1A2A2A Mean -30 (140) -12 (158) 0 (170) 12 (182) 30 (200) (reduces time)(adds time) GenotypeFreq Value Freq x Val A 1 A 1 p 2 30 p 2 (30) A 1 A 2 2pq 0 2pq(0) A 2 A 2 q q 2 (30) Sum = Pop Mean = 30(p-q) + 2(0)pq

a -a 0 Average Homozygote Midpoint (172.5) Timing of Metamorphosis (Days) Total Range =  a=110 Consider the joint effect of both TH Loci Th  A1A1 Th  A1A1 Th  A2A2 Th  A2A2 Overall Mean =  a(p-q) +  2dpq

Genotypic value is not transferred from parent to offspring; genes are. Need a value that reflects the genes that an individual carries and passes on to it’s offspring Empirically: An individual’s value based on the mean deviation of its progeny from the population mean. Theoretically: An individual’s value based on the sum of the average effects of the alleles/genes it carries. Breeding Value

average effect of A n :  n = mean deviation from the population mean of individuals that received A n from one parent, if the other parent’s allele chosen randomly  1 = q [ a + d (q – p)]  2 = –p [ a + d (q – p)]  1 = pa + qd - [ a (p – q) + 2dpq ] population mean. f (A 1 )f (A 2 ) Average Effect of an Allele Type of Values and FreqMean valuePopulation Average gamete of gametesof genotypesmean effect of gene A 1 A 1 A 1 A 2 A 2 A 2 a d -a A 1 p q pa + qd -a(p-q) + 2dpq q[a+d(q-p)] A 2 p q -qa + pd -a(p-q) + 2dpq -p[a+d(q-p)]

When there are only two alleles at a locus A1A1 A1A2 +ad A2A2 -a Average effect of a gene substitution (a - d)(d + a) p(a - d) +q(d + a)  = a + d(q - p)         p  