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This text provides an overview of early evidence indicating that most genes specify protein structure, as well as the work of Garrod and Beadle and Tatum on inborn errors of metabolism. It explains the flow of information from DNA to protein through transcription and translation, and discusses the structure and synthesis of RNA. Additionally, it explores mutations that can affect biochemical pathways, including base substitution, missense, nonsense, and frameshift mutations, as well as larger DNA segment mutations and the role of transposons.
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Early evidence indicating most genes specify the structure of proteins • Garrod’s work on inborn errors of metabolism in early 1900s • Beadle and Tatum’s work with Neurospora mutants in the 1940s
Mutationsaffectingbiochemical pathways
Information flow from DNA to protein • Transcription • RNA molecule complementary to the template DNA strand synthesized • Translation • Polypeptide chain specified by messenger RNA (mRNA) is synthesized
Structure of RNA • RNA • Formed from nucleotide subunits • Each nucleotide subunit contains ribose, a base, and three phosphates • Like DNA, RNA subunits are covalently joined by a 5΄—3΄ linkage to form alternating sugar-phosphate backbone
Transcription • Incoming nucleotides with three phosphates pair with complementary bases on the DNA strand • RNA polymerase cleaves two phosphates from each nucleotide and covalently links the remaining phosphate to the 3΄end of the RNA chain
Translation • Polypeptide chain specified by the mRNA is synthesized • Initiation • Repeating cycles of elongation • Termination • Each sequence of three nucleotide bases in the mRNA constitutes a codon • Requires tRNAs and cell machinery, including ribosomes
Coupled transcription and translation in bacteria • Unlike eukaryotic cells, in bacterial cells translation and transcription coupled • Translation of the bacterial mRNA molecule usually begins before the 3´ end of the transcript is completed
Retroviruses • Flow of genetic information is reversed by reverse transcriptase • Enzyme associated with retroviruses • Retroviruses synthesize DNA from an RNA template • Example of retrovirus is HIV-1, AIDS virus
Mutations • Base substitution mutations • Often result from errors in base pairing during replication • Missense mutations • Nonsense mutations • Frameshift mutations • One or two nucleotide pairs are inserted into or deleted from the molecule
Some mutations involve larger DNA segments • Due to change in chromosome structure • Wide range of effects as they involve many genes • DNA sequences that “jump” into the middle of a gene • Known as transposons or transposable genetic elements • Most are retrotransposons