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Berkeley MCELLBI 140 - Lecture Notes

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1MCB140 01-23-07 1Brilliant in Brünn, part II“With Pisum it was shown by experiment that the hybrids form egg and pollen cells of different kinds, and that herein lies the reason of the variability of their offspring. If it chance that an egg cell unites with a dissimilar pollen cell, we must then assume that between those elements of both cells, which determine opposite characters some sort of compromise is effected. The resulting compound cell becomes the foundationof the hybrid organism the development of which necessarily follows a different scheme from that obtaining in each of the two original species. With regard to those hybrids whose progeny is variable we may perhaps assume that between the differentiating elements of the egg and pollen cells there also occurs a compromise, in so far that the formation of a cell as the foundation of the hybrid becomes possible; but, nevertheless, the arrangement between the conflicting elements is only temporary and does not endure throughout the life of the hybrid plant. Since in the habit of the plant no changes are perceptible during the whole period of vegetation, we must further assume that it is only possible for the differentiating elements to liberate themselves from the enforced union when the fertilizing cells are developed. In the formation of these cells all existing elements participate in an entirely free and equal arrangement, by which it is only the differentiating ones which mutually separate themselves. In this way the production would be rendered possible of as many sorts of egg and pollen cells as there are combinations possible of the formative elements.”MCB140 01-23-07 2“Brilliant” isn’t strong enoughThis is “swish central”Nothing but net.Mendel’s data showed – to him – that in a heterozygote, the two alleles – A and a – remain DISTINCT and SEPARATE.They reach a compromise for the life of the plant, but then, during gametogenesis, they go their separate ways, unchanged.To describe this incredibly simple idea as influential would be akin to calling Michael Jordan a “pretty good shooting guard.”Sadly, this idea sat on the bench for the entire 1865-1900 season. More on why that happened – shortly. MCB140 01-23-07 3Charles Darwin (1859)The Origin of Species by Means of Natural Selection1. Living organisms multiply; resources are limited.2. Organisms vary. Some variation affects survival and reproduction.3. Like begets like.4. Populations of organisms will evolve: those organisms with characteristics most favourable for survival and reproduction will not only have more offspring, but will pass their characteristics onto those offspring.Æ the characteristics seen in the population will changeheritable change in animals Æ selection by environment Æ adaptation to environmentMCB140 01-23-07 4The problem with step 2 “What was missing from Darwin’s theory was a source for the variations on which natural selection acted. … Darwin addressed the problem of heredity. He believed that smalled units, which he called gemmules, were produced by the cells, and them migrated through the body, and some of them would be retained in the … gonads.” EA Carlson, Mendel’s Legacy“The most unfortunate of the assumptions underlying Darwin’s mechanism of evolution was that of blending heredity; i.e., that parental differences are merged in the offspring of bisexual reproduction so that variation is constantly being diminished. The basis for this assumption wsa the so-called intermediacy of hybrids which Koelreuter regarded as a law for all “true” hybrids.”R. Olby Origins of MendelismCopyright © 2006 by Sidney HarrisMCB140 01-23-07 5Sergei Chetverikov (1926)On certain aspects of the evolutionary process from the standpoint of modern genetics“mutational load”1. Trap 239 Drosophila melanogaster near Moscow.2. Self their offspring (brother-sister).3. 32 recessive loci (=186 in humans).“… A species, like a sponge, soaks up heterozygous mutations, while remaining phenotypically homozygous.”MCB140 01-23-07 6Archibald Garrod (1902)Higher frequency of children with alkaptonuria (urine turns dark on standing and alkalinization) from consanguineous marriages.Why?“There is no reason to suppose that mere consanguinity of parents can originate such a condition as alkaptonuria in their offspring, and we must rather seek an explanation in some peculiarity of the parents, which may remain latent for generations…”http://www.esp.org/foundations/genetics/classical/ag-02.pdf2MCB140 01-23-07 7Ah!“It has recently been pointed out by Bateson that the law of heredity discovered by Mendel offers a reasonable account of such phenomena. …”Garrod (1902) Lancet 2: 116.MCB140 01-23-07 8Garrod (1902) Lancet 2: 116.MCB140 01-23-07 9A useful termIf a trait follows in its inheritance Mendel’s first law, that phenomenon is described as “simple Mendelian inheritance” (SMI).Examples: cystic fibrosis; sickle cell anemia; hemophilia A.MCB140 01-23-07 10An awful, awful term:“monogenic trait”If a trait follows SMI – what does that say about its genetic architecture?A highly pernicious school of lack of thought in biological instruction uses the term “monogenic trait.” It is most unfortunate.MCB140 01-23-07 11 MCB140 01-23-07 123MCB140 01-23-07 13 MCB140 01-23-07 14MCB140 01-23-07 15XMCB140 01-23-07 16In what sense is blood clotting a “monogenic” trait?In no sense at all.What is “simple” is the GENETIC difference between an unaffectedindividual and an individual who has hemophilia. It can be as small as a single base pair change.In other words, what the phenotype tracking allows us to do is look at the genetics of the difference.If a particular phenotype follows SMI, then all that says is:The difference in genotype between an organism with that phenotype and without it is due to a genetic difference at a single position in the genome (=“a single locus”).Nothing can be learned from this analysis about the number of genes that are required for that phenotype to develop, or about the role this particular gene plays in having this phenotype develop.PKU, for example, has to do with the breakdown of aromatic aminoacids, and its lack causes mental retardation. What is the specific role of phenylalanine breakdown in cognition?MCB140 01-23-07 17Koopman et al. (1991) Nature 351: 117.XYXX+Sry transgeneManhood – a monogenic traitNote: SRY directly causes the conversion of a female embryo to


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Berkeley MCELLBI 140 - Lecture Notes

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