Chromosome theory of inheritance MCB140 01 26 07 3 MCB140 01 26 07 1 MCB140 01 26 07 4 Darwin s theory of evolution Crick s central dogma of molecular biology Galileo s theory that the Earth rotates around its axis and revolves around the Sun Other theories MCB140 01 26 07 2 Once he had isolated pure breeding lines for several sets of characteristics Mendel carried out a series of matings between individuals that differed in only one trait such as seed color or stem length Grrrrrr 1 August Weissman 1883 From Theory in the 1900s to Firmly Established Fact by 1920 MCB140 01 26 07 7 MCB140 01 26 07 5 Mendel s Particles of Inheritance the Genes Lie on Chromosomes soma Germ plasm soma Germ plasm Recall Darwin s gemmules MCB140 01 26 07 8 MCB140 01 26 07 6 1866 General Morphology of the Organisms The nucleus is the part of the cell that is responsible for heredity Nice idea but not based on data of any sort at the time Ernest H ckel 2 Beitrage zur kentniss der Zelle und ihre Lebenserscheinungen Contributions to knowledge about the cell and of aspects of its appearance that have to do with the fact that it is alive Salamander tail fin cells living cells Gills fixed cells Walther Flemming 1879 MCB140 01 26 07 11 MCB140 01 26 07 9 1 Cut off the tail of some mice 2 Breed the tailless mice 3 Get children with tails 4 Cut off their tails 5 Breed them Repeat 21 times Experiments done by others and cited by Weissman as supporting evidence centuries and centuries of foot binding by the Chinese and circumcision by the Jews have not led to the inheritance of either trait Weissman s somewhat gruesome but well persuasive experiment a process with threads mitosis MCB140 01 26 07 10 3 Theodor Boveri 1895 MCB140 01 26 07 15 MCB140 01 26 07 13 Flemming stained the cell with a dye and found that something inside the nucleus stained quite vigorously He called it chromatin stainable material In 1888 Waldeyer renamed Flemming s threads chromosomes The object that acquires a color after we stain it the chromosome MCB140 01 26 07 16 1 Enucleate sea urchin egg by agitation 2 Fertilize this cytoplasm only egg with sperm 3 To his surprise get a larva but a much smaller one It is not a given number of chromosomes as such that is required for normal development in as much as these fragments although they contained only half the normal amount of chromatin and half the number of elements namely the chromosomes of one sperm nucleus still give rise to normal plutei Pluteus easel Boveri expt 1 MCB140 01 26 07 14 What if anything do the chromosomes have to do with the process of heredity A question 4 MCB140 01 26 07 19 MCB140 01 26 07 17 Enucleate the egg of one species of sea urchin and fertilize with a sperm of a different species Boveri expt 2 MCB140 01 26 07 20 MCB140 01 26 07 18 5 MCB140 01 26 07 23 the next question was whether this unequal distribution of the chromatin is of any influence upon the properties of the four cells While the four blastomeres of a normally divided egg are absolutely equivalent to each other it is seen that the properties of the blastomeres of a doubly fertilized one are different from each other in diverse ways and to varying extent All that remains is that not a definite number but a definite combination of chromosomes is necessary for normal developemnt and this means nothing other than that the individual chromosomes must possess different qualities Boveri expt 3 ctd For that half of the class that did not answer the multiple choice question correctly MCB140 01 26 07 24 On chromosomes chromatids sisters nonsisters and homologs MCB140 01 26 07 22 Let s make a triploid sea urchin embryo by fertilizing an egg with two sperm The resulting zygote does divide but the mitotic spindles are multicentric Sometimes this triploid entity even produced a 4 cell embryo The resulting blastomeres when separated invariably failed to develop further In contrast the 4 blastomeres from a diploid embryo went on to form 4 plutei the maternal cytoplasm has no determining effect on the offspring but supplies only the material in which the sperm nucleus operates Inheritance is therefore affected by the nucleus alone MCB140 01 26 07 21 Boveri expt 3 E B Wilson 1896 6 MCB140 01 26 07 27 For now let us call EACH of those pieces a chromosome More later on that for now bit We can now ask those 35 000 genes mentioned earlier how are they distributed between those 23 chromosomes In alphabetical order perhaps Or which would be cool by pathway in order of appearance in Stryer For example chr 1 would all the genes for glycolysis chr 2 for the Krebs cycle and chr 3 for oxidative phosphorylation Or why not maybe different people have a different distribution of genes on their chromosomes In other words maybe my chr 1 has different genes than your chr 1 1 genome 35 000 genes 23 pieces of DNA MCB140 01 26 07 28 This issue has been studied experimentally and it was found that in a given species the distribution of genes between chromosomes and within each chromosome their order are both invariant In other words if we examine chr 1 by the way they are numbered according to size eXcept for the X then in every human being that chromosome will contain the exact same genes note I did not say the exact same allelic form of the genes simply the same genes With a few interesting exceptions no meaningful relationship has been found between the function of a gene product and its placement within the genome For example the X chromosome contains the second most important male gene the receptor for testosterone known as the androgen receptor the genes for two factors involved in blood clotting factor VIII and factor IX and the genes for receptors required for color vision Genetic unity of a species MCB140 01 26 07 26 In principle it is imaginable that each gene could be on a separate piece of DNA so the nucleus of a human cell would contain 35 000 separate pieces of DNA In actual fact in a human being the genome is distributed onto 23 pieces of DNA well 23 pieces plus one additional somewhat important gene on a separate small piece of DNA but more on that later What you call those pieces depends on who you are The human genome contains 35 000 genes Each gene is from a physical perspective a stretch of DNA The sequence of base pairs in that DNA encodes the amino acid sequence of a protein note this simplified narrative disregards noncoding DNA elements of a gene such as regulatory DNA stretches untranslated 5 and 3 UTRs introns and
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