indian 1 monroe halle_berry Snipes lucy_liu_014 426px-Robert_Redford_2005 Jackie_Chan_2002-portrait_edited 401px-Morgan_Freeman%2C_2006 whoopi-goldberg 45745715_Oldaboriginalmanweb Evolution as a two-stage process: 1. variation among individuals in a population 2. changes in the proportion of variants from generation to generation http://upload.wikimedia.org/wikipedia/commons/2/2e/Charles_Darwin_seated_crop.jpg R.A. Fisher The increase in mean fitness due to natural selection is proportional to the additive genetic variance in fitness. http://www.pbs.org/wgbh/evolution/library/06/1/images/l_061_01_l.jpg https://online.science.psu.edu/sites/default/files/biol011/Fig-6-1-Mendel-Cross-Breeding.jpg http://4.bp.blogspot.com/-pw-Y1VIiQJ8/ULWDHK0e3SI/AAAAAAAAMPw/9uY43HvMRO4/s1600/mendel+experiments. jpg Biometricians: continual variation many genes often strong influence of environment http://www-history.mcs.st-and.ac.uk/BigPictures/Galton_2.jpeg F. Galton http://image.slidesharecdn.com/b1topic1-continuousanddiscontinuousvariation-140413152151-phpapp02/9 5/4-b1-topic-1-continuous-and-discontinuous-variation-1-638.jpg?cb=1397461750 Paradox: for evolutionary biologists important to study phenotypes × for geneticists easier to directly study molecules Sources of phenotypic variation: differences in genotype differences in environmental conditions maternal influences (paternal influences) http://static.topyaps.com/wp-content/uploads/2013/02/Evolution-The-Modern-Synthesis-Julain-S.-Huxle y.jpg George Udny Yule Why don´t we observe the 3:1 ratio in populations? Reginald C. Punnett: brachydactyly http://www.dnaftb.org/images/5/Punnet.jpg B b B b bb Bb Bb BB •gene … till now difficult to define/delimit •locus … here = gene or any other molecular trait •alleles = alternative forms of genes (now broader meaning – segment of DNA) •genome = set of all genes of an individual (nuclear, mitochondrial...) •genotype = set of alelles of one or more genes of an individual • •haplotype (haploid genotype) = combination of alelles inherited together http://kidshealth.org/kid/talk/qa/headers_97314/what_gene1.jpg Genotype and allele frequencies Frequencies: genotype: P (fAA), Q (fAa), R (faa) allele (gene): p (A), q (a) P + Q + R = 1 p + q = 1 3.1.jpg Evolution takes place in populations… T. Dobzhansky, E. Mayr: population as a shared gene pool » set of shared alelles or gametes local populations (subpopulations, demes) global population, metapopulation http://www.webpages.uidaho.edu/wlf448/2010/Lab/Metapopfigure-lab11.jpg Evolution takes place in populations… T. Dobzhansky, E. Mayr: population as a shared gene pool » set of shared alelles or gametes local populations (subpopulations, demes) global population, metapopulation populations natural, experimental, agricultural, model Local populations also share a system of mating foto_011 Model populations – Hardy-Weinberg population Characteristics: diploid sexual reproduction discrete generations 2 alleles, „fair“ segregation 1:1 same frequencies of alleles in both sexes Characteristics: random mating (panmixis) non-random: assortative mating, inbreeding very large (effectively infinite) size no gene flow no mutation no selection Model populations – Hardy-Weinberg population Why don´t we observe the Mendelian ratios in nature? Godfrey Harold Hardy File:Ghhardy@72.jpg http://classconnection.s3.amazonaws.com/89/flashcards/4667089/png/brachydactyly-14423EE20494848DF9B .png R. C. Punnett http://www.dnaftb.org/images/5/Punnet.jpg 1908 HARDY-WEINBERG PRINCIPLE Godfrey Harold Hardy (1877-1947) File:Ghhardy@72.jpg File:Wilhelm Weinberg.jpg Wilhelm Weinberg (1862-1937) p2 + 2pq + q2 = 1 Father´s gametes Genotype frequencies in zygotes: 1. Alelle frequencies stable across generations = Hardy-Weinberg equilibrium (HWE) 2. HWE achieved within a single generation of random mating Generalization: X-linked genes: females: p2 + 2pq + q2 males: p + q more than 2 alleles: 3 alleles: p2 + q2 + r2 + 2pq + 2pr + 2qr in general pi2 + 2pij HARDY-WEINBERG PRINCIPLE 2_3 heterozygotes most frequent when p = q = 0,5 fAa decreases with 2pq faa decreases with q2 Þ fAa / faa increases ® rare allele „hidden“ for selection in heterozygous state Frekvencies of rare alleles Possible causes of HWE violation: Methodic causes: Violation of some of the assumptions of the H-W population: null alleles, allelic dropout Heterozygote deficiency: selection against heterozygotes nonrandom mating (inbreeding, assortative mating) structured populations (different allele frequencies, cf. Wahlund effect) Heterozygote excess: selection in favour of heterozygotes nonrandom mating (outbreeding, negative assortative mating) migration mutation GENETIC VARIATION IN POPULATIONS Methods of the study of genetic variation: protein electrophoresis + - analysis of restriction fragments (Southern blotting, RFLP, DNA fingerprinting) PCR, sequencing, NGS, microsatellites ... Finger Polymorfism and polytypy File:Heliconius mimicry.png Polymorfism: proportion of polymorphic loci (P) sample size usually finite Þ limit 5% (P0.05) or 1% (P0.01) number of alleles per locus (A; allele diversity, allele richness) mean observed heterozygosity (Ho) mean expected heterozygosity (He) = gene diversity nucleotide polymorphism (q) nucleotide diversity (p) Issue of the extent of variation in natural populations: [USEMAP] T.H. Morgan, H. Muller: „classical“ model limited variability [USEMAP] A. Sturtevant, T. Dobzhansky: „equilibrium“ model variation widespread GENETIC VARIATION IN NATURAL POPULATIONS HZ 1966: Harry Harris – humans; Richard Lewontin, John Hubby – D. pseudoobscura microsatellites, minisatellites → high mutation rate, high variability question to what extent protein electrophoresis representative? GENETIC VARIATION IN NATURAL POPULATIONS VARIATION AT MORE LOCI linkage proximity of loci = linkage valid H-W assumptions Þ formation of linkage equilibrium this proces can be slow Þ linkage disequilibrium (LD) coefficient of LD: D relation of D to recombination r : Causes of linkage disequilibrium: absence of recombination (eg. inversion) nonrandom mating selection recent mutation sample is a mixture of 2 species with different allele frequencies recent merging of 2 populations random genetic drift LD needn´t exist only between loci on the same chromosome! http://www.bio.miami.edu/~cmallery/150/mendel/sf10x1a.jpg = mating between relatives eg. repeated autogamy (self-fertilization, self-pollination): initial generation (HWE): 1/4 AA, 2/4 Aa, 1/4 aa 1. gen. of selfing: 3/8 AA, 2/8 Aa, 3/8 aa 2. gen. of selfing: 7/16 AA, 2/16 Aa, 7/16 aa 3. gen. of selfing: 15/16 AA, 2/32 Aa, 15/16 aa INBREEDING COEFFICIENTS 1. Pedigree inbreeding, F: = probability of autozygosity autozygosity: alleles identical by descent (IBD), always homozygous allozygosity: either heterozygote or homozygote (alleles identical by state, IBS) IBD - IBS Inbred population = pop. in which the probability of autozygosity due to inbreeding > in panmictic population F = probability that an individual inherited both alleles at a locus from the same ancestor (both alleles are IBD) 0 £ F £ 1 Inbred population = pop. in which the probability of autozygosity due to inbreeding > in panmictic population F = probability that an individual inherited both alleles at a locus from the same ancestor (both alleles are IBD) http://www.genetic-genealogy.co.uk/images/image113.gif a) Amenhotep I. and Aahotep II. 25% b) Aames 37.5% c) Hatsheput 25% d) Remaining in the pedigree are not inbred, ie F = 0 FIS = (He – Ho)/He -1 £ FIS £ +1 Ho= observed He= expected heterozygosity 2. System-of-mating inbreeding, FIS: = deviation from HWE F and FIS don´t measure the same thing! F is the individual measure, FIS is the group measure Př.: hutterites (anabaptists) of the Great Plains in USA and Canada: in spite of respecting the incest taboo this is one of the most inbred human groups known (F = 0,0255) caused by a small number of founders (Protestants from Tyrol and Carinthia, 16th century) http://upload.wikimedia.org/wikipedia/commons/1/1d/Anneken_Hendriks.jpg inbred Genetic effects of inbreeding: inbreeding changes genotype frequencies (increase of homozygote freq.) ´ allele freqs. don´t change affects all loci Obrázek1.jpg Leavenworthia alabamica Size inbreeding depresion diseases, reduced fertility and/or viability BUT! Not always must inbreeding be deleterious (eg. many species of embryophyte (land) plants are self-fertilising). Moreover, the inbreeding effects can differ within a single species depending on environment. Phenotypic effects of inbreeding: http://minicattle.com/images/minikent_02.jpg https://encrypted-tbn2.gstatic.com/images?q=tbn:ANd9GcRrssmFeh7wn0T398Ran4c-D_jeePD616jl_Ow9d9qVdTN OfC5- http://oregonstate.edu/instruct/css/330/six/images/doublecross2.gif Vadoma tribe, Zimbabwe (tzv. „Ostrich people“): ectrodactyly Mormons of Hilldale (Utah) and Colorado City (Arizona) Amazonia Indians aristocratic dynasties Inbreeding depression in humans: the Amish: haemophilia B, anemia, myotonic dystrophy, Ellis-van Creveld syndrome (dwarfness, polydactyly), defects in nail development, dental defects http://de.academic.ru/pictures/dewiki/68/Deux_pieds_1_an.jpg http://zena-in.cz/media/2011/02/02/4cecb9c64c80.jpg http://is.muni.cz/do/rect/el/estud/pedf/js14/grafomot/web/pics/02-03-07-polydaktylie.jpg http://upload.wikimedia.org/wikipedia/commons/0/0f/Lancaster_County_Amish_03.jpg Charles II of Spain: unnaturally big head, deformed mandible, weak body, difficulties with walking and other defects, mental and psychical defects, impotence, sterility Francis II: in some children mental retardation, hydrocephaly, seizures, some unable of living without assistence Soubor:Carlos II.jpg Soubor:Francesco I.jpg Human inbreeding depression: Maria_Theresia_as_child hybrid vigour (heterosis) Francis I of Lorraine Maria Theresa http://www.farmwest.com/images/client/BreedingCorn%20Fig%206.JPG Soubor:Joseph II Portrait with crown.jpg = higher probability of mating between individuals with the same phenotype can be caused by active mating preference but another causes can exist as well eg.: phytophagous insects – individuals living at different host species can mature in different times Þ more frequent mating between individuals of the same phenotype (confinement to the host) without active mating preference Þ this is only a positive phenotypic correlation assortative mating causes deficit of heterozygotes assortative mating causes linkage disequilibrium (LD) Differences between inbreeding and assortative mating: affects only locus (loci) connected with preferred phnotype × inbreeding affects all loci ass. mating is a powerful evolutionary force (strong LD at more loci) ´ inbreeding only strenghtens existing LD, and only in the case of selfing, in other cases recombination „more succesful“ ® reduction of LD http://i.istockimg.com/file_thumbview_approve/15482487/3/stock-photo-15482487-disgusted-young-woman -sticking-out-tongue.jpg http://andthatswhyyouresingle.com/wp-content/uploads/2012/09/Happy-woman-Fotolia_12331389_Subscript ion_XXL.jpg = preference of mates with different phenotypes results in intermediary allele frequencies, reduces LD eg. preference of males with different MHC (mouse, man) http://www.nature.com/nri/journal/v7/n7/images/nri2103-f2.jpg http://i.huffpost.com/gen/1400676/thumbs/o-SWEATY-MEN-facebook.jpg MHC