Mendelian Genetics. References for lectures 1 and 2. Overview of Genes I. Overview of Genes I. Variation is widespread in nature
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1 Week 1, Hilry Term Mendelin Genetics Biology Hon. Mods: Cells nd Genes Humn Sciences Prelims: Genetics nd Evolution Lecturer: Roslind Hrding emil: References for lectures 1 nd 2 Texts: Hrtwell et l. Genetics: From Genes to Genomes. 2 nd ed., McGrw Hill, 2000, Chpters 1-4 Griffiths et l. n Introduction to Genetic nlysis, 2000 Chpters 1-4 Homework tonight Revise the process of meiosis Lecture Notes: Weblern Overview of Genes I Overview of Genes I DN nd RN: the bsis for ll processes nd structures of life. The whole inherited (genetic) informtion of n orgnism is encoded in DN or RN nd clled the GENOME Genomes include both the GENES nd the noncoding sequences The Humn Genome: Genes: DN tht cn be trnscribed & trnslted into proteins (~1.5% of humn genome) Non-coding: DN tht my be trnscribed into mrn but is not trnslted; some is relted directly to genes for splicing & regultion, but most is not; much is repetitive Moleculr Genetics is the field of biology which studies the structure nd function of GENES, GENOMES, nd HEREDITY t the DN nd RN level. Moleculr genetics explins the diversity nd complexity of life in unifying terms of chemistry Underlying biochemicl processes re incredibly similr in the vrious diverse life forms Moleculr genetics provides mny tools for genetic nlysis nd mnipultion, with wide pplictions in biology But genetic nlysis hs much older history! Introduction to Genes II Vrition is widespred in nture The study of GENES nd HEREDITY t the phenotypic level hs long history. People hve long puzzled over questions of inheritnce Questions bout resemblnce: Why do children resemble their prents? How cn diseses run in fmilies? Questions bout diversity within fmilies nd within niml or plnt breeds: How cn two blck lbrdors hve litter of blck, brown nd tn puppies? re there rules bout why vrition ppers nd how it is trnsmitted between genertions?
2 The first pplied genetic prctice ws rtificil selection The modifiction of vrition in plnts nd nimls s domestiction, llowed hunters nd gtherers to settle in villges nd survive s frmers nd herders. mize Dogs were domesticted from wolves. rcheologicl evidence for domestiction trces bck 14,000 yers. By 1750: ~20 breeds By 1905: 76 breeds Now: breeds In 1837 Morvin sheep breeders hd problem Merino Sheep Selective breeding prctices hd produced vluble flocks of merino sheep tht mde lrge quntities of soft, fine wool. dilemm for Morvin sheep breeder He possesses n outstnding rm tht would be priceless if its dvntges re inherited by its offspring, but, if they re not inherited, then it is worth no more thn the cost of wool, met nd skin. Which would it be? Breeding prctices in 1837 offered no definite predictions. But one person ws thinking bout the problem: bbot Cyril Npp Some misconceptions of the time Hypotheses then used to explin inheritnce: 1) One prent contributes more to n offspring s inherited trits - e.g., ristotle contended tht it ws the mle nd tht fully formed homunculus ws inside the sperm 2) Blended inheritnce - the trits of the prents re blended in their offspring nd forever chnged (like blue nd yellow to mke green) Nicols Hrtsoeker 1692 bbot Npp speks to the sheep breeders bbott Cyril Npp presided over the ugustinin monstery in Brunn, in the province of Morvi, in ustri (now Brno, Czech Republic), centre of lerning in the sciences nd humnities. The ugustinin monstery
3 Wht bbot Npp sid Gregor Mendel Npp proposed tht breeders could improve their bility to predict which trits would pper in their offspring if they ddressed three questions: 1) Wht is inherited? 2) How is it inherited? 3) Wht is the role of chnce in heredity? The monks hd no nswers for bbot Npp s questions. Born Johnn Mendel in : Mendel, ged 21, entered the ugustinin monstery in Brunn Mendel (now clled Gregor) sent by Npp to University of Vienn to study physics (with Doppler), mths, chemistry, botny, pleontology & plnt physiology Returned from Vienn in 1853, begn genetics experiments in 1854, published results t ge 1865 t the ge of 43 Gregor Mendel: Fther of Genetics nd prticulr experimentl pproch Mny complex problems re most conveniently tckled using model. brillint mind The proper equipment pproprite biologicl mteril There re orgnisms tht, becuse of their ntomy or physiology, provide esy ccess to the mechnisms tht underlie interesting nd importnt physiologicl nd biochemicl problems Hns Krebs (1975) J. Expt. Zool. 194: Use model orgnism for experiments Mendel s model orgnism: Pisum stiv Mny economiclly importnt orgnisms re not idel for genetic nlysis Long genertion time Difficult to crete pure (true) breeding lines (due to high heterozygosity, out-breeding nture, inbreeding depression) Reproductive biology not gret - hrd to mte, few progeny Lrge size - difficult to mintin in resonbly-sized experiments (e.g., in lbortory, or grden) Model orgnisms re menble to genetic nlysis: Short genertion time Cn be inbred Simple reproductive biology Smll size Lrge numbers of progeny Grden pe
4 Why pes were good choice Why pes were good choice well chrcterised, cultivted plnt tht grew well in the monstery grden t Brno excellent for n experimentl pproch. They could be self-fertilised (selfed) - llows inbreeding There were pure-breeding lines - lwys bred true, producing the sme trit genertion upon genertion They could be redily cross-fertilised to crete hybrids between pure-breeding lines- crefully controlled mtings nd reciprocl crosses could rule out the effect of one prent versus the other Mendel could grow lrge numbers of plnts nd progeny llowing quntittive nlyses tht produced robust results which ided interprettion (sttistics come lter) dvntges of simple reproductive biology Stmens (produce pollen) Ovule (severl in pes) Pistil Why pes were good choice ntgonistic pirs xil Terminl Green Yellow Flowers Flowers Yellow Green Long Short Stems Stems Purple White Round Wrinkled Pes hve cler-cut cut (discrete/qulittive) trits Mendel could unmbiguously distinguish between two lterntive forms. (Contrst these with continuous/quntittive trit vrition.) Not just pes! Vrition expressed s discrete, lterntive forms of trit is common in nture. Pigment phenotypes in foxgloves mouse litter from two prents heterozygous for the yellow cot colour llele. Wht did Mendel observe? ntgonistic trits The mting of prents with ntgonistic trits produces hybrids. Inflted Pinched The hybrids of the seven ntgonistic trits chosen by Mendel resemble only one of the prents. xil Flowers Terminl Flowers Green Yellow The trit in n ntgonistic pir tht ws mnifest in the hybrid ws known s dominnt. Long Stems Short Stems Purple White Yellow Green Round Wrinkled
5 Dominnt trits Dominnce Inflted xil Flowers Green Long Stems Purple Yellow Round Reciprocl crosses reveled not only dominnce, but lso tht the dominnce of trit ws independent of the prent - It is immteril to the form of the hybrid which of the prentl types re used in the cross Some clssicl genetics terminology for describing breeding experiments P - prentl genertion F 1 - first filil genertion - the offspring derived from the prentl genertion F 2 - second filil genertion - the offspring derived from the F 1 genertion Self - n inbreeding cross tht involves individuls tht re geneticlly identicl (e.g., single plnt with itself, or between full siblings derived from true breeding prents) Hybrid derived from two different prents Monohybrid cross experiment involving hybrids for single trit Dihybrid cross experiment involving hybrids for two trits Mendel s monohybrid crosses reveled units of inheritnce, now known s genes Terminology needed for Mendelin genetics Locus - geneticlly defined loction - strictly speking, we don t know if it is the plce of only one gene or not - but it is trnsmitted s single unit. llele - lterntive form t given locus Dominnt - the llele tht mnifests itself regrdless of the other llele tht is present - indicted by n upper-cse letter (e.g., ) Recessive - n llele whose effect is msked when co-inherited with dominnt llele - indicted by lower-cse letter (e.g., ) Homozygous - when both lleles t given diploid locus re the sme - i.e., or Heterozygous - when there is one dominnt nd one recessive llele present t diploid locus i.e., Wht did Mendel figure out? Wht did Mendel figure out? Reppernce of recessive trit in F2 genertion disproves blending. Every individul crries two copies of ech gene one from ech prent. These segregte during gmete formtion. pure-breeding line crries two identicl lleles nd is homozygous. Hybrids crry two different lleles nd re heterozygous.
6 Mendel s Lw of Segregtion explins how genes re trnsmitted Ech member of gene pir segregtes from ech other into the gmetes, so tht one-hlf of the gmetes crry one member of the pir nd the other one-hlf of the gmetes crry the other member of the pir The lleles unite t rndom, one from ech prent, t fertilistion Mendel s results reflect bsic rules of probbility Prob (gmete is Y) = ½ Prob (gmete is y) = ½ Product rule for independent events occurring together Prob (event 1 ND event 2) = Prob (event 1) x Prob (event 2) e.g. ½ x ½ = ¼ Prob (progeny re YY) = ¼ Sum rule for independent, mutully exclusive events Prob (event 1 OR event 2) = Prob (event 1) + Prob (event 2) e.g. 1/4 + 1/4 = ½ Prob (progeny re Yy ) = ½ Prob (progeny re yellow) = ¼ + ½ Further crosses confirm rtios predicted by the Lw of Segregtion Look t the phenotypic rtios in the progeny for these two different crosses. genotype phenotype Is there better wy to keep trck of ll the possible genotype combintions nd their proportions? Becuse dihybrid crosses will be more complicted thn this! Dihybrid crosses revel Mendel s Lw of Independent ssortment Genes for pe colour (green or yellow lleles) nd pe shpe (round or wrinkled lleles) ssort independently. Genotypic rtio 1 : 2 : 1 Phenotypic rtio 3 _ : 1 visul summry of the cross is provided by the Punnet Squre. New combintions in F 2 compred with P
7 The Lw of Independent ssortment B B b b B b During gmete formtion the segregtion of lleles t one locus is independent of the segregtion of lleles of nother locus. Results in predictble rtios of phenotypes in the F 2 genertion s shown by Punnett squre Follows bsic lws of probbility B b B b B b BB Bb BB Bb Bb bb Bb bb BB Bb BB Bb Bb bb Bb bb Phenotypic rtio: 9 _B_: 3 _bb: 3 B_: 1 bb Mendel published in 1865 fter Mendel So then wht hppened? Mendel s s work st dormnt for 34 yers - untested, unconfirmed nd unpplied to Mendel s s frustrtion for 18 of those yers yers fter Mendel s deth - his work ws rediscovered by three reserchers: Crl Correns Hugo de Vries Erich von Tschermk Shortly therefter, Willim Bteson nd R.C. Punnett used Mendel s work s the bsis of investigtions into why hybrid flowers were unstble - work tht ws commissioned by the Royl Horticulturl Society nd which led to the coining of the words geneticl nd genetics Mendelin Genetics How do we reconcile the lws tht Mendel proposed with wht we now know bout genes? Wht do we now know bout genes? Genes re DN sequences. DN sequences re orgnised into chromosomes 1 cm = 10 3 mm 10 6 μm 10 9 nm genemech/west/reserch1.htm
8 For mny species chromosomes come in pirs Chromosomes come in pirs clled homologues. One of ech pir is trnsmitted from ech prent. One pir of chromosomes determines n individul s sex. The chromosoml bsis of heredity 1902 chromosome theory of inheritnce proposed bsed on microscopic observtions of segregtion of homologous chromosome pirs during gmete formtion chromosomes prllel the behviour of Mendel s units of inheritnce nd so it ws inferred tht they crried the genetic mteril (genes) Meiosis Q. Wht ws this lecture bout? Meiosis consists of one round of chromosome repliction nd two rounds of nucler division Meiosis produces gmetes. lleles of gene, crried on the homologous chromosomes, segregte during gmete formtion.. The bsic Mendelin principles of how phenotypes re inherited by the trnsmission of genes from prent to offspring Next lecture Genetic polymorphism
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