Walter Sutton 1902 03 MCB140 9 5 08 1 What was clear about meiosis 1 That it involves two consecutive cell divisions not one 2 That the number of chromosomes appears to be reduced as a result of that fact MCB140 9 5 08 2 Sutton s conclusions 1 Chromosomes have individuality 2 Chromosomes occur in pairs with members of each pair contributed by each parent 3 The paired chromosomes separate from each other during meiosis and the distribution of the paternal and maternal chromosomes in each homologous pair is independent of each other MCB140 9 5 08 3 MCB140 9 5 08 4 The most important fact in classical genetics both Mendel s first and second law are explained by the behavior of chromosomes during meiosis MCB140 9 5 08 5 On chromosomes chromatids sisters nonsisters and homologs MCB140 9 5 08 6 Fact 1 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 polyadenylation signals furthermore most of the RNA produced by the human genome is noncoding but you will learn that in graduate school if you go there MCB140 9 5 08 7 Furthermore 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 MCB140 9 5 08 8 1 genome 35 000 genes 23 pieces of DNA 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 MCB140 9 5 08 9 Genetic unity of a species 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 MCB140 9 5 08 10 A famous example The long arm of chr 7 in all humans contains a gene called CFTR cystic fibrosis transmembrane conductance receptor it encodes a transmembrane channel required for cation transport Note that the location of this gene on this specific position of this specific chromosome and the distribution of its coding sequence between exons and introns are invarant between humans MCB140 9 5 08 11 With rare exceptions the nature relative orientation and distance from each other of genes on a given stretch of a given chromosome is the same between different human beings For example in the overwhelming majority of humans some 700 000 bp 700 kb 0 7 Mb upstream of the CFTR gene lies a gene called MET this is an important fact in the history of genetics and will be dealt with shortly MCB140 9 5 08 12 What are you doing tonight Humans happen to be obligate sexual outcrossers propagation of our species can only occur through the fusion of two gametes each with its own genome That has an important consequence for the relationship between the life cycle of a human and the chromosomal composition of its genome MCB140 9 5 08 13 Ploidy A conventional adult cell of a human contains two complete sets of instructions for the construction of a human being One set of instructions was received from Mom and the other from Dad This means that a typical cell in a living human being contains not 23 but 46 pieces of DNA two chromosomes 1 one from Mom one from Dad two chromosomes 2 you get the point Humans are diploid their adult cells contain two complete copies of the human genome MCB140 9 5 08 14 Homolog By tradition the two copies of chromosome 1 that you inherited from your two parents are known as a homologous pair or a pair of homologs For example your chromosome 7 which is a piece of DNA with the MET and CFTR genes on it that you received from Mom has inside your nucleus a homolog a piece of DNA that you inherited from Dad that is approximately the same size and has the MET and CFTR genes on it and a large number of other genes that humans tend to have on chr 7 MCB140 9 5 08 15 Alleles I mentioned that the position of CFTR on that specific spot of chr 7 is invariant between humans It is the case however that when one compares the genomes of two different human beings one sees a difference on average once every 1 000 bp typically a single base pair change known as a SNP snip a single nucleotide polymorphism There are two very famous such polymophisms in the human genome and you are required to know both One is on chr 7 of the CFTR gene it is a deletion of a triplet TTT that encodes phenylalanine 508 in the primary amino acid sequence of that protein This mutation known as 508 causes cystic fibrosis in homozygous form The other is on chr 15 in the globin gene it is a point mutation A T that changes a glutamate to a valine in homozygous form this mutation causes sickle cell anemia MCB140 9 5 08 16 The outbred human especially the outbred American As you will learn later in the class humanity especially in the US exhibits a very high degree of admixture the union of genomes with different ancestral histories From a genomic perspective this means that if we take an average American and compare the
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