- From gene to protein!

 

Human genes and protein synthesis

Ü Human genes: They are units of DNA sequences that containing information which determine the composition of an RNA molecule and most often translated to a protein.

Ü Every three nucleotides "triplet" represent a single codon, coding for a particular amino acid. Some codons act as a “start” signal, whereas others serve as “stop” signals that terminates translation .

Protein synthesis steps (From gene to protein) 

1. DNA replication

ü  Replication is semiconservative, i.e. each daughter molecule receives one strand from the parent DNA molecule.

ü  Unwinding proteins, DNA-directed RNA polymerase, DNA polymerase and ligase are also required.

ü  DNA polymerases synthesize the new strand in a 5' to 3' direction.

ü  Discontinuous replication, i.e. one or both DNA strands may be synthesized in pieces known as Okazaki fragments, which are then linked together to yield a continuous DNA chain.

2. Transcription

ü  Synthesis of complete RNA molecules from DNA by the enzyme RNA polymerase.

ü  Transcription yields three types of RNA: mRNA, tRNA and rRNA.

ü  Each nucleotide in the mRNA is complementary to one in the DNA template.

3. Post-transcriptional processing: the initial transcript is edited to remove introns and splice exons together by means of an RNA-protein complex called the spliceosome. Multiple different transcripts may be produced (alternative splicing).

3. Translation

ü Protein synthesis according to the amino acid code in mRNA.

ü Takes place in cytoplasmic structure called ribosomes (consisting of ribosomal RNA and proteins).

ü  Four stages:

1)  Amino acid activation.

2)  Initiation of polypeptide chain formation begins with the amino acid, methionine.

3)  Polypeptide Chain elongation: triplet codons are recognized by tRNAs that include complementary anticodons and bind the corresponding amino acid, delivering it to the growing peptide.

4)  Chain termination. Three codons, UAA, UGA and UAG "stop codon" is reached, at which point translation ends and the peptide is released.

1.   Post-translational modification of proteins

Gives the mature protein functional activity and includes peptide cleavage and covalent modifications, such as glycosylation, phosphorylation, carboxylation and hydroxylation of specific residues.

Ü Gene structure: consist of:

1.  Exons (coding sequences): regions containing the code that ultimately corresponds to a sequence of amino acids.

2.  Introns (non-coding sequences): intervening sequence, which do not become part of the amino acid sequence.

3.  Regulatory sequences: Initiating and terminating codons, promotors (5′) and polyadenylation (3′) end.

 

Ü The number of genes is still not known precisely but appears to be around 30,000 in human genome.

Ü < 5% of the DNA codes for proteins, the remainder of the DNA, the portion not involved in protein formation, had been termed junk DNA, but recently it is found that much of this presumed junk DNA is functional and likely serves some regulatory function.

20 different essential amino acids but as there are four different types of bases, there are 64 possible combinations of three bases i.e. 4³ = 64 codes. Some of the codons represent stop signals that terminate protein synthesis, some amino acids are coded for by more than one triplet.

 

The distribution of these genes varies greatly between chromosomal regions & chromosomes. For example:

ü  centromeric regions are mostly non-coding, with the highest gene density observed in sub-telomeric regions

ü  Chromosomes 19 and 22 are gene rich, whereas 4 and 18 are relatively gene poor.