Lecture 1 The Basics of Heredity History of genetics History of genetics „pre-mendelian era“ •The effects of heredity are observed by human kinds form its down • •Children resembles of their parents •Domestication of animals and plants, •selective breeding for better traits • •People of Mesopotamia used hybrids of domesticated and wild donkeys to pull their war chariots about 4,500 years ago ( Y-chromosomal and mitochondrial DNA) • •Sumerians horse breeding records • • https://www.science.org/cms/10.1126/sciadv.abm0218/asset/e9e2ce63-f045-4f71-a219-050cd1b231c1/asset s/images/large/sciadv.abm0218-f1.jpg History of genetics: early Greek philosophers •Vapour theory (Pythagoras) •man body – embryo – uterus of female) • • •Fluid theory (Empedocles) •fluid from all parts of each parent create embryo • • • •Spontaneous generation (Aristotle) •Origin of live from decaying matter •Reproductive Blood Theory- embryo is produced due to the mixing of reproductive blood of the two parents • •Pangenesis (Hypocrates) •invisible “seeds ,” from organs of parents are like miniaturized building components and are transmitted during sexual intercourse, reassembling themselves in the mother’s womb to form a baby History of genetics: Middle age theories •1) Preformation theory (Malphigi, Swammerdan, Bonnet) •miniature individual of extremely small size is present in sperm or egg, grows into a new individual after it receives nourishment in the womb of a female •Spermists vs ovists – which cells bear key components for gender development? • ØDa Vinci – proposed equal contribution of parent´s traits to of spring ØVan Leeuwenhoek - animacules (aka sperms of mammals nad frog) are associated with eggs ØMalphigi, Swammerdan, Bonnet miniature individual of extremely small size is present in sperm or egg (hommunculus) • Introduction: Principles of Inheritance & Variation Notes | Study Biology Class 12 - NEET History of genetics: Middle age theories •2) Particluate theories – 18 - 19th century •Theory of Acquired Characters (Lamarck) Ønew character once acquired by an individual shall pass on to its progeny (neck of giraffes x Wiesmann – progeny of mices with cut tails had long tails…) • • Theory of Pangenesis (Darwin) Øgemmules or pangene partilces (of given, oragn, tissue etc) are carried by the blood to the reproductive organ and are deposited in the sex cells, which again carry them to the next generation. •Theory of Germplasm (Wiesmann) ØOrganisms with sexual reproduction carry two types of cells • - somatic cells make up body (somatoplasm) •- reproductive cells make up sperms and ovas (germplasm) Gregor Johann Mendel (1822-1884) •* 20th July 1822 Hynčice, North Moravia, •1840 – 1843 Philosophy at Olomouc University •1843 – join the Augustinian Abbey in Brno •1849 – 1851 - teacher at high school in Znojmo (Greek, Latin and German language, mathematics) •1851 – 1853 University of Vienna (math, – Doppler, deep understanding of statistics, Dawrin´s work (but Darwin did not known Mendel cause wrote in German language) •1854 – 1868 – teacher at Realschule at Brno (physics, biology) •1854 – 1863 first experiments with pea in abbey garden •1865 – series of lessons about his experiments in conference of biologists in brno (2nd and 3th of March) •1866 – publication „Versuche über pflanzen-hybriden“ (Experiments on Plant Hybridization) •1868 - abbot of St. Thomas' Abbey in Brünn •1881 – director of Moravian bank in Brno •6.1. 1884 – Mendel died from chronic nephritis, buried at Central Cemetery of Brno, Leoš Janáček played the organ at his funeral • • • • • • • • Mendel´s education – Natural science at university of Vienna (1851-1853) Experimental physics (prof. Doppler) Combinatorics, probability theories, mathematical description of results… Plant physiology (prof. F. Unger) „continuity of cells and cell lineage is necessary for birth to other organisms“ Doppler 250px-Franz_Unger Prof. Franz Unger: Botanische Briefe (1852) •Knowledge of basic principles of plant physiology, hybridization and plant selection combined with methodology of „hard data“ collection bring Mendel to idea of existence of discreet particles, which are located inside cells and responsible for expression of different traits •During his studies, he developed a theoretical model of transfer of the traits from one generation to another with the use of those particles • •He returned to Brno with this „project“ Wild pea (Pisum sativum) - model object of Mendel´s experiments 14-01-GeneticCross-L •True - breeding, self - pollinating plant with big blooms • large number of varieties • easy to grow, regular and steady yield • possible control of plant fertilization • 7 pairs of chromosomes (2n = 14) • Breeding Mendels´ s experiments - character of traits 7 traits – stand alone, binar („yes or no“) •34 varieties – 2 years of observing - 22 varieties with steady difference of traits Parental varieties = homozygotes (AA, aa) - differences: 1.Seed shape: round / wrinkled (chromosome 7) 2.Seed color: white / bright yellow or green (chromosome 1) 3.Bloom color: white / purple (chromosome 1) 4.Pod shape: inflated / constricted (chromosome 4) 5.Pod color: green / yellow (chromosome 5) 6.Flower position: axial / terminal (chromosome 4) 7.Stem length: 1,9 – 2,2 m / 0,24 – 0,46m (chromosome 4) 1 pair of trait observed in parental (P) generation offspring - 1st (F1 ) and second (F2) generation DOMINANT trait overcome in F1 RECESIVE trait, which shows itself in generation F2 Example of monohybrid crossing: height of the pea plants (tall / dwarf) Monohybrid, Dihybrid, Cross, Backcross And Testcross •2 identical copies of gene (alleles) segregate into gametes Obsahuje obrázek: THE PUNNETT SQUARE APPROACH FOR A MONOHYBRID CROSS F1 monohybrid (heterozygote) carry 2 different unique alleles in given proportion 50% (0,5) gametes are joining randomly YY (0,25), Yy (0,25)*2, yy (0,25) Identity of reciprocal crossing A cross, with the phenotype of each sex reversed as compared with the original cross, to test the role of parental sex on inheritance pattern identical results in F1 F1 F1 There is no difference if trait comes from mother or father! A a A AA Aa a Aa aa heterozygote x heterozygote P: Aa x Aa A a A AA Aa A AA Aa dominant homozygote x heterozygotee P: AA x Aa dominant homozygote x recessive homozygote P: AA x aa a a A Aa Aa a aa aa recessive homozygote x heterozygote P: aa x Aa a a A Aa Aa A Aa Aa gametes Gametes of a monohybrid - Aa Mendel identified that heterozygote parents create gametes with one of their two allele with same exact probability … but how can prove this? A A A a a 50 % A, 50 % a Backcrossing - what kind of gametes and in what ratio are present in hybrids? •B1 z – backcrossing of F1 hybrid with parent with recessive alleles for given trait (Aa x aa) • • sherlock B1 Aa x aa Gametes of hybrid will join with gametes of a parent carrying recessive alleles = highlighting the combination of alleles in gametes of the offspring! 2 types of gametes R, r ; ratio 1 : 1 B1 – 2 phenotypes; ratio 1 : 1 Only 1 type of phenotype P: RR x rr F1 Rr With recessive parent With dominant parent Round Wrinkled Round •Backcrossing B1 B1 „analytical“ B1 „non-analytical“ Mendel´ s conclusions from the monohybrid crossing •Each trait (f.e. shape of the seed –round/wrinkled) is controlled by a some form of inheritance factor or determiner (now known as genes) •Every parent has a pair of genes in for every trait in all cells of the organism •Genes are transferred to the next generation by sex cells •F1 generation from two true-breeded varieties has one allele dominant over another, which is recessive. Those tow together create allelic pair •F1 offsprings show only one parental trait - dominant •The results of reciprocal crossing were all the same no matter whether which parent transferred dominant or recessive allele • Mendel´ s conclusions from the monohybrid crossing •only one of the two gene copies present in an organism is distributed to each gamete (egg or sperm cell) that it makes, and the allocation of the gene copies is random. • LAW of SEGREGATION • • •Gametes fuse randomly and without regard to other associated gene pairs •Trait not shown in F1 generation reappeared in F2 generation in 25 % offsprigns and the most importantly •Traits had qualities same in offsprings, did not blended and behaved as distinct units! • • • • Dihybrid Cross – 2 traits, are they inherited independently? Image result for Dihybrid Cross •Connection of two dominant and two recessive traits • •Each parent is homozygous for 2 genes = 2 allelic pairs • •Gametes – one allele from each pair • •Alleles of both pairs segregates INDEPEDENTLY = • •Dihybrid RrYy creates 4 types of gametes • • lDiagonals of heterozygotes and homozygotes lBreed novelties novel homozygous combinations different from parents Two possibilities pf parental crossing !!! Gametes: RY ry Ry rY Punett square Dihybrid cross Phenotype ratio 9 R-Y- Round yellow 3 R- yy Round green 3 rr Y - wrinkled yellow 1 rr yy – wrinkled green Genotype ratio 4 phenotypes Dihybrid cross Backcrossing n- level of hybridism Aa – n=1 AaBb – n=2 AaBbCc – n=3 Number of different genotypes Nr. of gametes of hybrid Nr. of different zygotes Nr. of different homozygotes * Nr. of raising novelties Phenotype ratio of F2 generation** Genotype ratio of F2 generation Generalization for n-hybridism In all given allelic pairs In case of complete dominance in all allelic pairs General Mendel's conclusions from dihybrid crossing •F1 hybrids express only one variant from both parental traits – always dominant. •F2 generation present novel variants completely different from parents ( in our example yellow-wrinkled and round-green seeds). The exist because of new combinations of parental genetic material = recombinants • • Recombination of hereditary factors (genes) is made according to laws of probability. Alleles of given genes are in each generation chosen randomly (alleles of different genes are combined independently) • •LAW OF INDEPENDENT ASSORTMENT • •Hybrid F2 generation showed all combinations of parental traits in specific ratio 9:3:3:1 (full dominance) Mendel´s discoveries: overview •Traits are inherited as discreet pieces (elements) • •Units of heredity (genes) 1)are material in nature 2)come in pair (inherited from mother and father) 3)they are twofold: dominant or recessive (hidden) 4)they are transmitted to the next generation via sex cells 5)they are inherited separately - they are not blended in nature • •F1 offsprings show only one parental trait (dominant one) • •Heterozygous alleles segregate into gametes in random fashion • •Alleles of different genes segregate (combine itself) independently of each other Mendel´s sweet pea traits… nowadays ...ATCGGGAATCGGACCCGATG… ...ATCGGGAATCGTGACCGATG… Dominant alelle Recessive alelle - mutant • https://dr282zn36sxxg.cloudfront.net/datastreams/f-d%3A3502463cda7ce6976375ce6c8b3c5999dab1cb786c95 da47302eb2a7%2BIMAGE_TINY%2BIMAGE_TINY.1 Mutation in pea genes create new allele! Seed shape – round x wrinkled RR x rr •Cause of creation of r allele (wrinkled): •Mutation (transposone insertion) in gene which encode enzyme participating on creation of starch in seeds (SBEI) – development of inactive version of the enzyme •Result: •Accumulation of sacharose in seeds – change of osmotic pressure – wrinkled shape of the seeds after drying • Bhattacharyya et al. (1993) a) The reason for segregation and combination of alleles is the behavior of chromosomes during meiosis I (spacing of chromosomes during anaphase I of first meiotic division) b) The principle of combination apply for genes located on different chromosomes Pp P p Meiose I - Anapahse spacing of homolouge chromosomes Mendel´s principles and chromosomes Description of genes and alleles on metaphase chromosomes Gene A A A Metaphase chromosome = 2 identical chromatids! Genotype AA A A A Genotype Aa ? l Karyotyp A A a a B B b b C C c c D D d d Genes freely combinated Linked genes (on same chromosome AaBb CcDd dihybrid EE f f monohybrid Ef Human Karyotype - mitosis Exceptions from Mendel´s ratios lIncomplete dominance lCodominance lMultiple allelism lLethal alleles l lPenetrance lExpressivity l lPleiothropy lPhenocopy l l Gene linkage 32 Effect of alelles of one gene Gene interactions Aa – exactly 50% Aa – not in half Phenotype effects of dominance exceptions lFull dominance Incomplete dominance Codominance Incomplete dominance – Antirrhinum majus Color of bloom depends on amount of product Allele R1 - color production Heterozygote R1R2 – approx.. half amount of color production compared to R1R1 R2R2 - no color 34 Explanation Incomplete dominance – human familial hypercholesterolemia lHereditary disease, incidence 1/250 in CR, cca 500 mutations described lCaused by high levels of LDL (low density lipoprotein) cholesterol lFH gene heterozygotes have approx.. only half amount of LDL receptors responsible for cholesterol lHomozygotes in FH gene have no receptors – very rare SCAN046 Correction 35 xanthomas Brain and heart attacks risk at age 20 years Codominance – human blood groups Co Dominance - Mendelian Concepts - MCAT Content What do you mean by codominance? Explain it with example of blood groups in human beings. •Gene I – chromosome 9, 3 alleles IA, IB, I •Total of 6 genotypes •Heterozygotes AB express both antigens (both alleles active) •Codominant alleles A and B, both dominant to i •Importance – blood transfuses, paternity testing, .. • Recessive lethal allele in humans – Tay Sachs disease lMutation genu HEXA (enzyme hexozaminidase A absent) lAbnormal accumulation of lipid complex GM2 ganglioside on the surface of neurons (function: protection of cells) due to absence of degradation process of GM2 lNewborns are normal lAfter 6 moths of age – neurological degradation, mental retardation, deafness, blindness, at 2 years unable to move, death usually 3-4 years lAshkenazi Jews - heterozygotes Aa 1 : 30 (incidence 1:3600) hqdefault 37 Tay-Sachsova choroba, lysozomální genetická porucha ukládání, 3D ilustrace. Dítě s makrocefalií, a detailní pohled na oteklé neurony s lamelární inkluzí v důsledku hromadění gangliosidů - Fotografie, Obrázek Tay-Sachsova-choroba-1 Tay-Sachsova-choroba-2 Penetrance and expresivity lIncomplete penetrance – individuals do not show given trait, even though they have given genotype lVariable expressivity - the of expression of gene differs in individuals carrying same trait (different phenotype lReason – effect of environment, genetic background…1 38 Penetrance and Expressivity Impact Genetic Reporting Difference Between Penetrance and Expressivity in Tabular Form Incomplete penetrance: polydactyly lThe trait is conditioned by a dominant mutant allele P lIts expression is showed in just a few individuals expresses lInfluenced by genetic background snu5e_fig_04_10a snu5e_fig_04_10b Mutation effect not expressed – healthy individuals figure-03-16 https://www.youtube.com/watch?v=OxehHPwTFtk&ab_channel=Shomu%27sBiology Phenocopy traits induced by environmental effects are identical to phenotypes caused by genotypes 42 Phocomelia – inherited malformations of human arms and legs Teratogenic effect of thalidomide taken during early pregnancy Gene interactions lTraits are based on cooperation of more genes (pathways) l lGene interactions – quantitative traits arise from cooperation of two and more allelic pairs from different genes l lIf two genes interact with each others, same rules as in dihybridism applies (same for n – hybridism) l lDifferences are detectable in phenotypes – in cases gene interactions there is lower number of phenotype classes Gene interactions lEpistasis dominant / recessive –in dominant epistasis, the dominant allele of one gene masks the expression of all alleles of another gene, while in recessive epistasis (Dahlia variablis bloom colors) –the recessive alleles of one gene mask the expression of all alleles of another gene. –Typical example – color of dogs coat lComplementarity - –both dominant alleles are necessary for creation a product ( L. odoratus) lInhibition –inhibitive allele has not another effect on phenotype than ability to suppress an effect of dominant allele (Feathers color of domestic fow) lMultiplicity –bilateral relation of alleles of interactive genes, but in comparison with complementarity, each single dominant allele of any of these genes, even in itself, is sufficient for expression of a corresponding trait. – a) non-cumulative (Siliqua shape of shepherd’s purse) - phenotype is determined any dominant allele – b) cumulative: (number Caryopsis color of wheat) - expression of phenotype is based on number of dominant / active alleles – Interaction of two genes changes in F2 ratios lDihybrid crossing Inhibition Complementarity Recessive epistasis Dominant epistasis Duplicity non-cumulative Duplicity cumulative (dominant) Heredity of sexuality and sex-linked traits lEvolution – asexual to sexual and haploid to diploid organisms lReason = to maximize to genotype variability lSexual organisms – change of haploid / diploid stage, reduction of diploid number of chromosomes (meiosis) lSome organisms can reproduce asexually or can change periods of sexual /asexual reproduction lThe most of the eukaryotic organisms use sexual reproduction Heredity of sexuality and sex-linked traits lBasic features of sexuality are the same in all eukaryotes – there are two types of sex (sexual organs with production of male or female gametes) and new generation arise from connection of both gametes lAnisogamy - difference in size of male / female gametes lEvolution of separate sex leads to creation l of haploid gametes - meiosis Man 1012 sperms per life Woman 2,5 millions of oocytes only 400 will mature Heredity of sexuality and sex-linked traits lSexual differentiation lPrimary differentiation –Include creation of reproduction organs (gonads) lSecondary differentiation –Include differentiation of other organs (mammary glands, genitalia, etc.) l lOrganisms can carry –A) just one type of gonads (male / female) dioecious (plants) , gonochorism (animals, higher mammals) l - The sex in gonochorism is determined by genetic traits (GSD) or by environmental factors (ESD) –B) both male and female gonads at same time - monoecious, hermaphrodites Discovery of sex chromosomes alternativní popis obrázku chybí lAutosomes (somatic) x gonosomes (sex chromosomes) lHumans 22 pairs of autosomes + 1 pair of gonosomes lDesignation of sex chromosomes: X and Y (or Z and W) lXX: homogametic sex (one type of gametes) lXY: heterogametic sex (two types of gametes) lAA: two batches of autosomes l lThere are 3 basic systems of chromosomal determination of sex l mammal type – (Drosophila) l bird type – (Abraxas) l type Protenor Chromosomal determination of sex Chromosomal determination of sex: Mammal type lFemale sex: AA XX - homogametic lMale sex: AA XY – heterogametic lEach pair produce 50% of sons and 50% of daughters = sex ratio 1:1 lCarriers of the sex traits are males lTwo types of sperms are produced with l same probability lEggs are always of same genotype (X) lMammals, insect, reptiles, several plants The chromosomal basis of inheritance (article) | Khan Academy The chromosomal basis of inheritance (article) | Khan Academy Mammal type of sex determination in plants – dioecious type of plants chmel01 295px-Cannabis_flowering Kopriva prew XX female and XY male plants lDesignation of genotypes ZW - females, ZZ males lCarriers of sex traits – females (2 types of eggs – Z,W lMales produce only one type of sperm (Z) lChromosome Z – locus of DMRT1 gene – development of male gonads require 2 copies lIf one copy is disabled – females Chromosomal determination of sex – bird type Mechanisms of Sex Determination | Definition, Examples, Diagrams Chromosomal determination of sex – type Protenor lProtenor (Lygaeus kalmii) lFemale sex: AA XX - homogametic; Male sex: AA X - heterogametic lMostly insect species Lygaeus kalmii.jpg Protenor (Lygaeus kalmii) Sex ratio 1 : 1 Females – 14 chromosomes Males – 13 chromosomes Chromosomal determination of sex: haplo - diplpoidy lFemales: AA - diploid lMales: A - haploid lOrder Hymenoptera l(bees, ants, wasps) lBees –no sex chromosomes – sex is determined by total number of chromosomes –Fertilized eggs (2n) produce females –Un-fertilized eggs (1n) - parthenogenesis = males –Females have on average 75 % of common genes – higher genetic affinity – high level of social cooperation 75 % 50 % 100 % n=16, 2n=32 C:\Users\Uzivatel\Desktop\Petr\Obecná genetika\Chromosomy\v_trubec.jpg Environmental sex determination (ESD) lSex is determined by external factors f. e. a)Temperature (reptiles) - genetics (XX/XY or ZZ/ZW)+TSD (temperature dependent sex determination) – a) a) a) a) a) – b) Social factors - Bonellia viridis –If egg develops in isolation = females –If egg migrates into the tract of female = males –Males 1000x smaller than females l M. Crighton - Jurassic park (Spielberg movie 1993) 4885951428_f77756d865 Obrázky Bonellia – procházejte fotografie, vektory a videa 9 | Adobe Stock Genetic determination in humans l lPresence of different sex chromosomes and product of one specific gene SRY (sex-related region Y) determine the phenotype (sex) of the individual l lExpression of SRY activate the cascade of events leading to development of female or male gonads (master-switch sex determining gene) l l Determination of sex in humans – significance of chromosome Y 951809AK 45,X – females 47,XXY- males X - 1669 genes Y – 200 genes (50-60 genes protein-coding) david Karyotype: Male 46,XY Female 46,XX Proof of chromosome Y is responsible for sex determination Genes located on chromosome Y Structure of the human Y chromosome. The Pseudo Autosomal Regions [PAR1... | Download Scientific Diagram Stock vektor „X Y Chromosomes On White Background“ (bez autorských poplatků) 2056106576 | Shutterstock •Sex differentiation, sperm production •10-15% sequences comes from chromosome X •Cca 60 millions of base pairs •Spermatogenesis - genes encode 9 protein families in 2-35x copies Development of sex in humans llong-term process – start at 1st trimester lactivation of 37 proteins + sex hormones lEnded after individual sexual maturation 60 61 Men – 25 years sperms – 265 divisions Men - 50 years sperms - 840 divisions !!! Spermatogenesis - 64 days DNA replication – errors in the process - mutations in older men Women – 24 cell divisions Differences in development of gametes in humans 62 Heredity of sex-linked genes l lGonosomes (X,Y) are consisted of two regions carrying genes – heterologous and homologous l • Non-homologous regions - determine genes with full sex-linked inheritance • Homologous regions - determine genes with incomplete sex-linked inheritance (= Mendel´s laws) l –Genes with loci of Y non-homologous regions determine holandric traits (father to son – Y-linked inheritance) –Genes with loci in non-homologous regions of X chromosome - X-linked inheritance l l Webquest Creator 2 XY XY l Morgan's Discovery of New Ratios (2016) IB Biology - YouTube T.H. Morgan 1910 l“Certain factors follow the distribution of the X chromosome and are therefore supposed to be contained in them.” lGenes lie on chromosomes !!! Sex-linkage heredity 65 Mendel´s law of uniformity of F1 hybrids and identity of reciprocal cross does not apply here !!! Non-uniform! CROSS heredity ! Sex-linked heredity D. melanogaster Genes located on non-homologous region of chromosome Y Rules of sex-linked inheritance (Morgan 1910) 1.If an individual carry dominant sex-linked trait (gene), whole F1 population will show same trait as dominant parent regardless of sex. In F2 there will be ratio 3:1 in this trait and individuals carrying recessive variant (allele) will be same sex as recessive 2. 2.If individuals with homogametic sex carry recessive sex-linked trait (gene), there will be shown both dominant and recessive variants but in opposite sex than in parents. In F2 regeneration the both variants will manifest with same frequency in whole population and in population of given sex l X-linked recessive inheritance lRecessive allele in males – hemizygous (only one member of chromosome pair) lProduce affected males in most times l1) XAXA x XaY (women healthy) –Healthy sons; daughters = carriers of the disease lXAXa x XAY (women carrier, man healthy) –½ sons affected, ½ carriers –Rare cases in women: daughters of affected man + woman carrier; women with 45,X karyotype lExamples: DMD, Hunter disease l l https://nci-media.cancer.gov/pdq/media/images/802198.jpg X-linked recessive Haemophilia: 1/10000 in men; 1/100 000 in women žen – pedigree of europeanm ruling houses snu5e_fig_05_09b snu5e_figun_05_p104a 69 Alexej