bch 5045 graduate survey of biochemistryhort.ifas.ufl.edu/faculty/guy/bch5045/lecture files/lecture...
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Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
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BCH 5045
Graduate Survey of Biochemistry
Instructor: Charles Guy Producer: Ron Thomas Director: Glen Graham
Lecture 16
Slide sets available at: http://hort.ifas.ufl.edu/teach/guyweb/bch5045/index.html
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.
• LEHNINGER • PRINCIPLES OF BIOCHEMISTRY
• Fifth Edition
David L. Nelson and Michael M. Cox
© 2008 W. H. Freeman and Company
CHAPTER 8
Nucleotides and Nucleic Acids
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.
The building blocks of nucleic acids!
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.
What is this monosaccharide and what does it have to do with DNA?
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Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.
The building blocks of DNA and RNA. What is the major difference between DNA and RNA and what biochemical significance does it have?
The estimated half-life of the 3’ P---O—C part of the phosphodiester bond to hydrolytic cleavage by water in DNA at 25°C is in the neighborhood of 31 million years while the same bond in RNA has a half-life of about 1 year. See commentary on next slide.
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.
The Genomes of Neandertals and Modern Humans As indicated on the previous slide, DNA is a pretty stable molecule for good reason, and this is largely why it is possible to obtain DNA or genomic sequence information from something or someone who lived 10s of thousands of years ago. All that is needed is the right environmental and microbiological conditions for antediluvian DNA, even highly contaminated with bacterial DNA, to be sequencible by modern methods and technologies. In 2010 Reich, Pääbo and colleagues reported on the analysis of nuclear DNA sequences extracted from a finger bone found in Denisova Cave in southern Siberia. They conclude that their sequencing results suggest an unexpected complex history of migration and colonization of Europe and Asia after modern humans presumably moved out of Africa 50,000–60,000 years ago (1). Previously, genetic data and the fossil record favored a so called “replacement model” with respect to Neandertals (or Neanderthal either way is correct) in which modern humans derive their greatest genetic ancestry to a breeding population with an origin in Africa about 200,000 years ago (2, 3, 4, 5), but not from Neandertals. The new nuclear genome sequence from the Siberian cave (1) and another sequence for Homo neanderthalensi (6) suggest that the out-of-Africa replacement hypothesis may need revision.
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Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.
It appears that the Denisovan sequence and previously determined Neandertal sequences are indeed related, but are not the same. Instead the Denisovan sequence is more closely similar to modern humans than has been found in other Neandertal sequences. Now the interesting part is that the Denisovan sequences cluster slightly better with present-day European or East Asian genomes than with African genomes, which is consistent with the view of some gene flow from Neanderthals to the progenitors of the ancestors of modern-day Eurasians (6). Unexpectedly the Denisovan Cave sequence seems to show a higher genetic relatedness with present-day island Melanesians. Overall, from the genome sequences it appears that there could have been limited gene flow from Neandertals to modern humans at two different times in different parts of the world, in Eurasia (early) and in Oceania (later). Still Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Germany notes that the Neandertal and modern human genomes share 99.5-99.9% nucleotide sequences identity.
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The Green et al. report (6) suggests that between 1 to 5% of non-African individuals’ genomes has an actual Neandertal origin, while Reich et al. results (1) suggest that 4 to 6% of the genomes of Melanesians are derived from the sequence from the archaic hominin population finger bone from the Denisova Cave has become known as the Denisovans. Yet, a more recent work (7) on Neandertal genome sequences has indicated an admixture between Neandertals and the expanding population of modern humans, H. sapiens who left Africa between 80,000 and 50,000 years ago to colonize the rest of the world. There is evidence for a significant presence (9% overall) of a Neandertal-derived X chromosome segment in all contemporary human populations outside Africa. Similarly, the analysis of 6092 X-chromosomes from populations that inhabit all continents seems to further support the assertions that a “mosaic of lineages” formed at different times and of different geographic locations contributes to the genetic constitution of modern humans. The analyses indicate an early admixture between an expanding African migrant population and Neandertals prior to or early in the out-of-Africa expansion that led to the successful colonization of the world by modern humans.
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Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
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The most recent Neandertal site dates to about 28,000 years ago. What happened to them remains unknown, but is the subject of much speculation. 1. Reich, D. et al. Nature 468, 1053–1060 (2010). 2. Cann, R., Stoneking, M. & Wilson, A. Nature 325, 31–36 (1987). 3. Ramachandran, S. et al. Proc. Natl Acad. Sci. USA 102, 15942–15947 (2005). 4. Underhill, P. et al. Ann. Hum. Genet. 65, 43–62 (2001). 5. Klein, R. The Human Career 3rd edn (Univ. Chicago Press, 2009). 6. Green, R. E. et al. Science 328, 710–722 (2010). 7. Yotova, V. et al. Mol Biol Evol. Jul;28(7):1957-62. Epub 2011 Jan 25.
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Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.
Hold on, there are additional purine and pyrimidine bases that can be found in DNA and RNA that we typically don’t hear much about. Of those shown, which nucleic acid would you expect them to be found?
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Products of RNA hydrolysis. Alkaline conditions promote RNA hydrolysis.
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Tautomers of uracil. Other bases found in nucleic acids have tautomeric forms also. Tautomerization is the interconversion of keto group to alcohol.
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Nucleic acids have a beginning and an end. How can we tell which is which?
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
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Nucleic acids have absorbance peaks near 260 nm. This physical property of nucleic acids, especially DNA, has everyday implications and consequences.
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
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What type of weak bonding interaction between the two strands of DNA shown serve to provide stability to the double helical structure of DNA?
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
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http://www.youtube.com/watch?v=wpoCbd3bb68
Images from the Text are protected by Copyright (c) 2008 by W. H. Freeman and Company, and by the licensors of W. H. Freeman and Company. Living Graphs software (c) 2008 Sumanas, Inc. ALL RIGHTS RESERVED.
Commentary by the instructor is protected by Copyright (c) 2011. ALL RIGHTS RESERVED.