In 1909, British physician Garrod first suggested that genes determine the phenotype through the action of enzymes that catalyze specific chemical reactions in the cell, claiming that the symptoms of a hereditary illness result from the inability of an individual to produce a certain enzyme.
Another decisive proof of the hypothesis that a gene produces a specific enzyme, given by Beadle and Tatum with their studies on the mold of bread.
Not all proteins are enzymes, so it is fair to say that a gene is a polypeptide.
The genes contain the instructions for the construction of the proteins, but DNA does not produce them directly, which deals with RNA, which is chemically similar to DNA with the difference that contains ribose instead of thymine, is also constituted Almost always from a single filament.
In DNA or RNA, monomers are the four types of nucleotides that stand out for their nitrogen bases, and genes are usually made up of hundreds or thousands of nucleotides, each with a specific base sequence.
Nucleic acids and proteins contain information written in different chemical languages.
To pass DNA from the protein to the protein, two steps are required:
- Transcription: This is the synthesis of RNA directed by DNA, where information is simply transcribed with the same language from one molecule to another.
- A DNA strand serves as a mold for the construction of a sequence of RNA nucleotides, which is a faithful transcript of gene expression instructions for the synthesis of a protein, and this RNA is referred to as RNA messenger (mRNA).
Transcription takes place in the nucleus and the mRNA is transferred to the cytoplasm where ribosome translation occurs.
Prior to abandoning the nucleus, the mRNA undergoes modifications before it becomes functional, in 2 stages, the pre-mRNA stage and finally the primary transcript (the final mRNA).
So recapitulating: DNA -> RNA -> protein.
There are only 4 nucleotides to specify 20 amino acids, but it has been found that the gene flow information to the protein is based on a triplet code, where genetic instructions for a polypeptide chain are written in the DNA in the form of a series of Words consisting of 3 nucleotides (thanks to which there are 64 possible coding units more than sufficient for each of the 20 amino acids).
During the transcription, the gene determines the triplet sequence within an mRNA molecule, where for each gene only one of the two DNA filaments is transcribed, and this takes the name of mold filament.
An mRNA molecule is not identical to its complementary filament where U (corresponding to T of DNA) pairs with A and C with G.
The nucleotide trunks of the mRNA are referred to as codons, which are read in the 5 'to 3' direction along the mRNA, and each codon indicates which of the 20 amino acids will be incorporated into the corresponding position of a polypeptide.
All 64 codons were decoded around the mid-1960s and it was found that each codon has specific functions or specific proteins, for example the AUG codon has a dual function, encodes the aminoacid methionine and the starting signal to the encoding process (Start codon), in addition, in an mRNA filament, the remaining 3 codons do not encode amino acids, but are stop translation signals (termination codons).
The genetic code is reminiscent but not ambiguous.
By summing up: genetic information is coded in the form of a sequence of triplet bases (codons) that do not overlap and each of which during protein synthesis is translated into a specific amino acid.
The genetic code is almost universal, with the exception of some translation systems where codons differ from normal ones, but this almost universal language has to have been functioning since the early stages of life history.
Synthesis and maturation of the RNA
RNA polymerase is an enzyme that separates the two DNA filaments and binds RNA nucleotides together, this enzyme can only add nucleotides at the 3 'end of the growing polymer so that the RNA stretches in the direction 5' -> 3 '.
The sequence of DNA to which RNA polymerase binds to the initiation of transcription is called the promoter, the sequence ending the term is called the terminator.
The promoter sequence is upstream of the terminator, and the portion of DNA that is transcribed in RNA is called a transcript unit.
Eukaryotes possess 3 types of RNA polymerases (I, II, III) and the one used for the synthesis of mRNA is II.
The promoter indicates which of the 2 filaments of DNA is used as a mold, and in the eukaryotes a group of proteins said transcription factors mediate the binding of RNA polymerase and the beginning of transcription.
Polymerase RNA may bind to the promoter only after some transcription factors are bound to it, and when both are related, it is said to be the beginning complex of the transcription.
Another crucial sequence of DNA promoter is the TATA box.
Once the polymerase is bound to the promoter DNA, the 2 filaments of DNA are performed and the enzyme begins to transcribe the mold filament.
The elongation is occurring while the RNA polymerase moves along the DNA by continuing to twist the double helix, adding nucleotides at the 3 'end of the growing RNA, the double helix of DNA regenerates and the new RNA molecule stops From his mold.
In the eukaryotes, the transcription rate is 60 nucleotides per second.
A single gene can be transcribed simultaneously by several RNA polymerase sequences that follow, and this increases the amount of transcribed mRNA.
Termination: Transcription proceeds until the polymerase RNA transcripts the sequence of a DNA terminator stopping hundreds of nucleotides after the AAUAAA signal of the pre-mRNA and at a distance of 10 to 35 nucleotides downstream of AAUAAA the pre- MRNA is cut, releasing from the enzyme.
The cutting site is also the site for the binding of a poly (A) tail.
Each end of a pre-mRNA molecule is modified, end 5 'is covered with a modified guanine, called the 5' cap which serves to protect the mRNA from degradation and is a signal of attachment to cytoplasmic ribosomes.
End 3 'is bound by a poly (A) queue that prevents RNA degradation and is also implicated in ribosome attack, and also seems to facilitate the export of mRNA from the nucleus to the cytoplasm.
RNA splicing allows to remove a large portion of the initially present RNA molecule (in the eukaryotes initially it is 8000 nucleotides, when enough is 1200).
Most eukaryotic and RNA genes possess long non-coding nucleotide sequences that are not translated.
The non-coding nucleic acid portions that lie between the coding regions are called introns, the other regions that are usually translated are called exons.
RNA polymerase transcribes DNA introns and exons, but introns are removed by splicing mRNA.
Splicing is done by short nucleotide sequences at the ends of snRNP introns, consisting of proteins and RNAs (snRNAs).
By joining the proteins they form the spliceosome, which interacts with the splicing sites by cutting the intron and joining the two extremes of the remaining exon.
Ribozymes are introns RNA molecules with enzymatic activity that allow to catalyze their removal.
Introns are important because they contain sequences that control gene activity and have discontinuous genes (composed of introns and exons) to encode more than one type of polypeptide.
Alternative splicing of the RNA is when some genes give rise to 2 or more different polypeptides, depending on which portions are treated as exons during the maturation of the RNA.
This splicing may be why men are so diverse, though having a very low genetic kit, just twice that of the fruit fly.
Domains are those regions of structurally and functionally distinct proteins born through discontinuous genes, and exons different encode different domains of a protein.
Introns increase the chances of increasing cross-over-crossing.
The synthesis of proteins
The translation interpreter is the RNA transfer (tRNA) that transfers amino acids from the cytoplasmic to the ribosomal pool, which adds these amino acids to the polypeptide chain extension end.The tRNAs are not all equal when one of them reaches the ribosome, carries a specific amino acid bound to one end, while at the other end there is a triplet of said anti-codon nucleotides, which appears on a complementary codon of the mRNA.The genetic message is then translated into a codon after the other as the tRNAs carry the amino acids in the expected order and these are linked by forming a ribosome chain.In the eukaryotes the tRNA is produced within the nucleus of the cell and must be transferred to the cytoplasm, and each molecule of it is formed by a single 80 nucleotide RNA filament that folds onto itself forming a molecule with a three-dimensional structure L form, where at one end there is the anticodone and at the other end there is the 3 'end, the linking site of the amino acid.There are about 45 tRNA molecules, some of which possess anticodies that recognize 2 or more different codons.The oscillation is the least rigid of anti-coding rules, and it explains why different codons that encode the same amino acid differ only in their third base (that is, the third U base of the tRNA can fit, for example, with A or G of the mRNA ).Anti-conjunction codon binding must be preceded by a proper coupling between the tRNA and its amino acid, and this bond is made by the amino acid-tRNA synthase enzyme, of which there are 20, each for each amino acid.Ribosomes favor the coupling between tRNA antibodies and mRNA codons during protein synthesis.The ribosome consists of 2 subunits, the major subunit and the lower subunit, both constituting ribosomal RNA (rRNA), which constitutes 2/3 of the mass of a ribosome.The ribosome has 3 mRNA binding sites: the P site links the tRNA that carries the chain into growth, site A links the tRNA carrying the amino acid that needs to be added to the chain, site E is where free tRNAs abandon The ribosome.The ribosome holds close tRNA and mRNA and positions the new amino acid by adding it to the carboxylic acid end of the nascent polypeptide.The synthesis of a polypeptide chain consists of 3 phases: start, elongation, termination.Beginning and elongation need energy consumption supplied by GTP hydrolysis.The initiation involves the association of the tRNA mRNA carrying the first amino acid of the polypeptide and the 2 ribosome subunits.In the elongation, amino acids are added one at a time to the previous amino acid, and occur in a 3-cycle cycle: codon recognition, peptide bond formation, transfer.Termination is the last stage of the translation where the elongation continues until it finds a stop codon (triplet UAA, UAG and UGA) in the ribosome site A of the mRNA, and then site A binds to one Protein said release factor which involves the polypeptide hydrolysis at Site P, causing its release from the ribosome.
An mRNA molecule is usually used to produce several simultaneous copies of a polypeptide, thanks to several ribosomes that operate simultaneously.
When a ribosome moves beyond the start codon, another ribosome may bind to the mRNA, and so on, forming a polybosomal, a structure that speeds up the production of polypeptides.
After the synthesis, the polypeptide begins to wind up to reach the proper structural shape for its functioning, conformation determined by the primary structure, in turn determined by the gene.
The chaperone protein favors the proper folding of the polypeptide so that it is a functional protein, while the phenomenon of denaturation is when the protein loses its shape and becomes inactive.
There are 2 types of ribosomes, free ribosomes and ribosomes bound.
The free radicals are suspended in the cytosol and synthesize soluble proteins that will function in the cytosol, the bound ones being attached to the wrinkled endoplasmic reticulum ERr and produce proteins for internal membrane systems and proteins that can be exported out of the cell.
Free and bound ribosomes are identical and can be exchanged for space.
The synthesis of all proteins begins in the cytosol and terminates them, unless the nascent peptide pushes ribosome to bind to ER.
The polypeptides for membrane systems therefore have a signal peptide that directs them towards the ER.
The signal recognition particle (SRP) promotes the link between the ribosome and the receptor membrane protein of the ER, where it resumes synthesis and removes the signal peptide.
Types of eukaryotic RNAs
| RNA messenger mRNA | Carries information from DNA to ribosomes |
| RNA transfer tRNA | It transduces the codons of the mRNA into amino acids |
| RNA ribosomal rRNA | It performs catalytic and functional roles within ribosomes |
| Primary transcript (eg pre-mRNA) | It is a precursor to mRNA, rRNA and tRNA |
| Small SNRNA nuclear RNA | It has structural and catalytic roles in spliceosomes |
| SRP RNA | Complex of RNA and proteins that recognizes the peptizes signal of polypeptides directed towards ER |
Point mutations
Mutations are genetic material modifications, point mutations are chemical modifications charged by a single pair of bases of a gene.
If a point mutation occurs in a gamete, this can be transmitted to the progeny, and if mutation has an effect on the phenotype, it is termed hereditary disease.
Point mutations can be divided into 2 categories: base pairs substitutions and base pair insertions or deletions.
Replacements consist of replacing a nucleotide and its partner on the complementary filament with another pair of nucleotides.
A variation of a pair of bases can transform a codon into another that is translated from the same amino acid by making a silent mutation, or not affecting the protein's functioning, while other substitutions may involve amino acid substitution but will not affect the Same function of the protein.
In other cases, amino acid substitutions involve modifying protein functions, in some cases creating new functionalities, while others may damage their normal functioning.
Replacements are usually sense mutations (missense), that is when the modified codon still encodes an amino acid and therefore has a meaning, not necessarily correct, instead the substitutions that make a stop signal are referred to as nonsense mutations and almost All lead to the production of non-functional proteins.
Intakes and deletions are mutations where the nucleotide pair is added or lost, and are dysfunctional mutations because they can alter the reading grid in the said shift grid shift mutation phenomenon (Frameshift mutation), which will occur each time the number of nucleotides is not multiple of 3, and unless this shift takes place at the end of the gene, it will produce a protein almost unworkable.
Other errors can occur through spontaneous mutations, mutations involving large DNA fragments.
Mutagens are physical and chemical agents that interact with DNA causing mutation.
They can be X-rays, ultraviolet light, and may impersonate improperly during DNA replication, or replicate the DNA by inserting inside it and forming a twin helix distortion, while others modify the bases chemically, altering the 'pairing.
Much of the carcinogens are mutagenic and most mutagens are carcinogenic.
The gene may have different definitions, can be considered a hereditary unit that can envision a phenotypic character, may be the locus synonym, can be a portion of a specific nucleotide sequence along a DNA molecule.
It can be said that a gene is a region of DNA whose end product is a polypeptide or a RNA molecule.