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Chapter 3Proteins
TE Creighton
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EvolutionIn nature the macroscopic diversity we see stems from a molecular unity.
All organisms use the same 20 aminoacidsAll organisms use the same nucleotides for DNA, RNAThe aminoacids are all L amino acidsRibose units of DNA and RNA arre all D isomers.The basic properties of the proteins in E.coli and Humans are the same.The function of DNA and RNA pertains, but the differences between procaryotes and eucaryotes becomes significant
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EvolutionThe biochemical similarities extend to even higher levels of organisation
Biochemical pathwaysMetabolism
All this can be explained so far, with the presence of a common ancestor for all living organisms.This cell had already acquired all basic biochemical features.
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EvolutionThe diversity at higher level of organisation has arisenFrom Darwinian divergenceBut the most basic functions of an organism have been conserved.Reason for this: any alteration in these functionsLETHAL !!!!!!!!
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Evolution
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EvolutionComparisons at the macroscale: comparisons of the organsims, the fossil recordBut even more compelling is the comparison on the protein level.These studies provide deeper insights into how evolution works
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EvolutionE.g. A DNA chain of of only 1000 nucleotidesCan exist with any one of 4 1000 different nucleotide sequences.A small protein of 100 aminoacids can have 20 100different sequences.Compared to the mere numbers of possible proteins the existing proteins are determined by their ancestersAn existing protein serves its function. The variation is within the limit of function.’
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Primordial origins of lifeLife started out of a primordial soupWhere all components have been made out of simple moleculesForming the primordial soupAll the processes have been deomnstrated in the laboratoryThe chicken‐egg problem of molecular biology:Who cames first DNA,RNA or protein
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The accepted pictureSince the finding of Ribozymes:First RNA and RibozymesThereafter proteinsAnd DNA since DNA is chemically more stable as RNARemainders of thsi RNA world are:mRNAT‐RNARibosomes (hybrids RNA‐Protein)Coenzymes: ATP, NAD+, FAD composed of RNA moieties
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Evolutionary divergence of proteinsSimilar sequences mean descent from a common ancestor.The number of possible RNA,DNA or protein sequences is so great that it is implausible that similar long sequences could have arisen by any mechanism other than divergence from the same ancestor.Proteins and nucleic acids that have evolved from a common ancestor are homologous.After the first replication, mutations have started in the two sequences
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Homologous genes and proteinsProteins and genes are either Homologous or NOT.Either or not from a common ancestor.
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Homologous Genes and ProteinsThe other explanation Than divergence isConvergenceConvergence means two different sequences have acquired the same function ality and share a certain degree of homology.It exists at the macroscopic level but there are no instances where it could have been shown conclusively for nucleic acids and proteins.But it can not be dismissed
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Sequence alignments
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Diagonal dot blot
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Mutation and Protein structure
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Mutation and protein structure
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Reconstructing evolution
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Reconstructing evolution
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Reconstructing evolution
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Phylogenetic trees
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Phylogenetic trees
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Phylogenetic trees
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Rates of Divergence
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Rates of divergence
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The nine most ancient protein folds
c.37: P‐loop containing NTP hydrolase
a.4: DNA/RNA binding 3 helix bundle
Deoxycytidine kinaseEngrailed
homeodomain
c.1: 8‐stranded α/β barrel
Triose phosphate isomerase Glyceraldehyde phosphate dehydrogenase
c.2: NAD(P) binding Rossman fold
Ribosomal protein S6
d.58: Ferredoxin‐like
Flavodoxin
c.23: Flavodoxin‐like
Ribonuclease H
c.55: Ribonuclease H‐like
Pyrophosphatase
b.40: OB fold
Adenine methyltransferase
c.66: SAM‐dependent methyltransferases
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Not all widely diversified and broadly functional folds are ancient
Adenine nucleotide binding protein
Scop C.28: also called ‘HUP’ domains
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Gene rearrangements
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Gene rearrangements
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Gene rearrangements
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Gene rearrangements
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Paralogous comparison
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Elongation by intragene duplication
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Gene fusion and division
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Hybrid protein by mismatch recombination