Walter Sutton, 1902-03What was clear about meiosisSutton’s conclusionsSlide 4The most important fact in classical geneticsOn chromosomes, chromatids, sisters, nonsisters, and homologsFact 1Furthermore1 genome = 35,000 genes = 23 pieces of DNAGenetic unity of a speciesA famous exampleSlide 12“What are you doing tonight?”PloidyHomologAllelesThe outbred human (especially the outbred American)Important consequence of thatSlide 19Slide 20Inside a cellDivisionHmmmmBrace yourselves“Sister”??!!If you think about it …Slide 27Bleh, part IISister chromatidsWhat is going on?!!The X filesNonsister homologSlide 33Slide 34Mitosis vs. meiosisSlide 36Slide 37Slide 38What is being omitted for lack of timeSlide 40William BatesonSlide 42Slide 43Archibald Garrod (1902)Ah!Slide 46Two factsEnter the fruit flyMCB140 9-5-08 1Walter Sutton, 1902-03MCB140 9-5-08 2What was clear about meiosis1. 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 3Sutton’s conclusions1. 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 4MCB140 9-5-08 5The 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 6On chromosomes, chromatids, sisters, nonsisters, and homologsMCB140 9-5-08 7Fact 1The 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 8FurthermoreIn 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 91 genome = 35,000 genes = 23 pieces of DNAFor 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 10Genetic unity of a speciesThis 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 11A famous exampleThe 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 12With 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 13“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 14PloidyA 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 15HomologBy 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 16AllelesI mentioned that the position of CFTR on that specific spot of chr. 7 is invariant
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