M.B.Ch.B, MSC, DCH (UK), MRCPCH

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Presentation transcript:

M.B.Ch.B, MSC, DCH (UK), MRCPCH Molecular Biology Lec.3 Dr. Mohammed Hussein M.B.Ch.B, MSC, DCH (UK), MRCPCH

Translation

The Second Stage in gene expression is translating the nucleotide sequence of a mRNA molecule into the amino acid sequence of a protein.

Genetic Code The genetic code is defined as the relationship between the sequence of nucleotides in DNA (or its RNA transcripts) and the sequence of amino acids in a protein.

Codon Each amino acid is specified by one or more nucleotide triplets (codons) in the DNA.

Number of codons There are 4 nitrogenous bases in DNA & RNA Adenine, Guanine, Thymine (Uracil), Cytosine Each codon = 3 bases, so we have: 43 (4x4x4) = 64 codons

20 Amino Acids

AGC

AGC

Stop Codons 61 codons code for amino acids. The other 3 (UAA, UAG,UGA) are stop codons (or nonsense codons) that terminate translation.

Start (Initiation) Codon There is one start codon (initiation codon) AUG, coding for methionine. Protein synthesis begins with methionine (Met) in eukaryotes

Important features of the genetic code include The code is unambiguous. Each codon specifies no more than one amino acid. The code is degenerate. More than one codon can specify a single amino acid. All amino acids, except Met and tryptophan (Trp), have more than one codon. The code is universal (the same in all organisms). Some minor exceptions to this occur in mitochondria. The code is commaless (contiguous). There are no spacers or “commas” between codons on an mRNA. Neighboring codons on a message are nonoverlapping.

Mutation A mutation is any permanent, heritable change in the DNA base sequence of an organism. This altered DNA sequence can be reflected by changes in the base sequence of mRNA, and, sometimes, by changes in the amino acid sequence of a protein.

Types of Mutations Silent Missense Nonsense Frameshift mutation Large segment deletion Splice site mutation Trinucleotide repeat expansion

Large Segment Deletions Large segments of DNA can be deleted from a chromosome during an unequal crossover in meiosis β-thalassemia Cri- du-chat

Mutations in Splice Sites Mutations in splice sites affect the accuracy of intron removal from pre-mRNA during posttranscriptional processing. If a splice site is lost through mutation, spliceosomes may: Delete nucleotides from the adjacent exon. Leave nucleotides of the intron in the processed mRNA. Use the next normal upstream or downstream splice site, deleting an exon from the processed mRNA.

Mutations in Splice Sites Mutations in splice sites have now been documented in many different diseases, including ß-thalassemia Gaucher disease Tay-Sachs.

Trinucleotide Repeat Expansion

Translation (Protein Synthesis) The process of protein synthesis occurs in 3 stages: Initiation Elongation Termination

Elongation

Termination