Chapter 4 genetic
Expression of genetic heritage and realization of phenotype
I. From DNA to proteins
How is the information encoded by DNA transmitted to the cytoplasm, where the amino acids that form
proteins are assembled?
Proteins:
These are organic macromolecules essential to the functioning of the cell. They play
several functions including:
Transport (e.g. hemoglobin)
Catalysis of biochemical reactions (e.g. enzymes)
Communication between cells (e.g. neurotransmitters and hormones)
Structure and cytoskeleton (e.g. hair and hair keratin). Structure :
Proteins are formed of one or more polypeptide chains. Each polypeptide is a chain of amino acids
which are small organic molecules. There are 20 amino acids that form proteins, these amino acids
bind to each other by peptide bonds.
Proteins never retain a linear shape, they have a 3-dimensional structure, because the amino acids
react with their neighbors according to their chemical affinities. Thus, proteins take a characteristic
shape responsible for their properties and functioning.
A. Genes control protein synthesis: (doc2, p89 ) (analysis of document2)
- By comparing the positions of nucleotides existing on DNA with the positions of corresponding
amino acids on protein sequences, it was found that the change in nucleotides (mutations) causes a
change in the amino acid in the polypeptide chain.
- It was also found that the sequence of nucleotides in a gene indicates the chain of amino acids
that make up a protein is the collinearity gene/protein.
- From these two points it was understood that the gene is the plane of protein manufacture.
B. Gene expression in proteins :
This is the process that the cell uses to produce the protein molecules it needs to
read the genetic code written in DNA. Because DNA is very large and fragile to
leave the nucleus, it is transcribed into an mRNA that passes through the
cytoplasm where the cell interprets the genetic code and translates it into
proteins.
The steps of expression:
1. Transcription of DNA into messenger RNA: (nucleus)
A. Transcription of DNA into pre-messenger RNA .
B. Maturationof pre-messenger RNA to messenger RNA.
2. Translation of messenger RNA into protein. ( cytoplasm)
1. Transcription of DNA into messenger RNA : (activity 2 doc 1,2)
The pre-messenger RNA transcription:
- An enzyme, the RNA polymeraseva form a complementary chain of DNA matrix strand
by incorporating nucleotides (A-U, T-A , G-C and C-G ). The DNA strand of the matrix is called
the transcribed strand. Thus, the RNA message will be identical to that of the untranscribed
strand , unlike the presence of U in place of T. (course diagram).
- Copies of the gene are made in the nucleus, pass through the pores of the nuclear
envelope into the cytoplasm, as a messenger RNA. (course diagram). These molecules are
destroyed in the cytoplasm after a short time, they are ephemeral copies.
. Several RNA polymerase sequences along the same DNA segment to make multiple copies of
the gene in the form of messenger RNA.
-
Messenger RNA (ribonucleic acid)
It is a molecule of composition comparable (similar) to that of DNA, it is formed by a sequence of
nucleotides of four different types. However, the RNA molecule is different from DNA in several aspects:
it is formed of a single chain (1 strand), the sugar is the ribose and not the deoxyribose, the nitrogenous
base U (uracil) replaces the T (thymine), it is shorter (1 gene only) its life span is shorter.
How do you explain that in multicellular eukaryotes, the total length of the gene is sometimes five
times greater than that of the mRNA exported into the cytoplasm (comparison dot plot between
mRNA and mRNA)? (activity 5 doc1)
b. Maturation of the precursor RNA:
DNA is a sequence of coding and non-coding sequences, including within the gene. By
transcription of RNA, a true copy of the gene is formed, which is the pre-messenger RNA.
This molecule is formed by alternating portions that code for the polypeptide chain (the
exons) and other portions that will not serve for protein synthesis (the introns). The mRNA
that passes through the cytoplasm is much shorter than the copied gene. One must think
that a stage of maturation took place in the nucleus.
The pre-messenger RNA undergoes maturation or splicing, by elimination of introns and
binding of exons. RNA m is formed.
Explain why the “one gene, one protein” postulate was challenged
As the research results indicated that the genome is between 20,000-25,000 genes and that the
proteome (the set of proteins produced) is much larger between 100,000 and 1 million, the one
protein gene postulate was questioned.
However, depending on the type of cell or the time of expression of a gene, the pre-messenger
RNA may undergo different splicing and therefore certain exons may or may not be retained
in the m (mature) RNA. This phenomenon affects 60% of our genes, and gives greater genetic
flexibility by allowing one gene to code for several different proteins. If all introns are
systematically eliminated, not all exons are necessarily retained.
In some species, gene fragmentation is more important than the total number of genes.
Translation of the RNA messenger
a. The genetic code: (activity 3)
It is the system that matches the nucleotides of DNA (genetic information) with the amino
acids in a protein, associating each triplet or codon with an amino acid.
The codon, or triplet of nucleotides (doc 1 p92) is the sequence of three consecutive
nucleotides that code for an amino acid. Initiation or stop of transcription (stop codon). There
are 64 codons (4 ʒ) for designer 20 amino acids. Three tripletsne code for no amino acid
( UAA-UAG-UGA), these are the STOP codons.
The genetic code is REDUNDANT (repetitive) There are several codons to designate an amino
acid. On the other hand, each triplet codes for only one aa, so the it is UNIVOQUE (not
ambiguous). (1 codon = 1 aa). The genetic code is common to all living beings ( except one or
two exceptions), it is UNIVERSAL.
b. The synthesis of proteins takes place in the cytoplasm at the level of RIBOSOMES which are
organelles formed by two sub-units. A small, capable of recognizing and attaching to the mRNA and a
large associated sub-unit that is able to assemble the aa and bind them by peptide binding.
Several ribosomes succeed each other on the mRNA to perform the synthesis of several (10-20)
identical polypeptide chains. This set of ribosomes is called the polysome.
c. Translation: takes place in several stages:
1. Initiation : It starts from the initiator codeAUG (coding for methionine)
2. Elongation of the polypeptide chain: The ribosome moves from triplet to triplet adding the
corresponding aa and binding them together by peptide bonds.
3. The wave end assembly continues until the ribosome reaches the STOP (UAA or UAG or
UGA) ducodon reading. The ribosome dissociates and releases the protein that is formed.
- The protein will undergo changes such as suppression of methionine in first position.
The DNA-Protein relationship
Regulation of gene expression
All cells in an organism have the same genetic information, since all these cells are from a
single egg cell that has been divided by mitosis. However, a cell expresses only part of the
genes it possesses. By expressing different genes in each type of cell, the cells thus
specialize.
Indeed, signals internal or external to the body, of a very varied nature, are likely to trigger
fixation on the regulatory sequence of the gene present on the DNA, proteins called
transcription factors. Once fixed, these transcription factors interact with the ADNet RNA
polymerase to initiate or stop transcription of a gene.
« Gene expression is finely regulated, in space and over time.”
example of a gene to be expressed as "PITX1" and a regulatory sequence "PEL" upstream of the gene.
There is a relationship between the genotype (all the alleles that a cell has = its genetic
heritage) and its molecular phenotype (the proteins it possesses which are the result of RNA
transcription and translation into a polypeptide chain).
Different individuals have different alleles , the proteins formed will be differentand so the
molecular phenotype will be different.
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The genotype determines the phenotype at different scales:
The phenotype of an individual is the set of characteristics that define all living beings:
morphological, anatomical and physiological character. (observable or measurable
characteristics). Since the organism is composed of cells, themselves composed of molecules,
the molecular phenotype of a cell determines the cellular phenotype and therefore that of
the organism (macroscopic).
The cells have, for each of its genes, either two times the same allele (homozygous
individual) or two different alleles (heterozygous individual).
Example of the genotype and phenotype of blood group ABO:
The [A] phenotype may have a
homozygous (A//A) or
heterozygous (A//0) genotype
The expression of these different alleles in different proteins is responsible for the molecular
phenotype, which, therefore, can define the characteristics of the living being from the
molecule to the individual.
The study of genetic diseases, due to the presence of at least 1 defective allele of a gene,
(example: sickle cell disease, xeroderma pigmentosum) shows that the molecular phenotype
(abnormal proteins (examples hemoglobin, enzymes or others) is the cause of symptoms found
at the cellular level and therefore at the body level.
Understanding how gene expression is regulated involves, among other things, better
knowledge of the sequence of genes and messenger RNAs. This is possible thanks to
equalization techniques . This can be used to link a disease with the abnormal proteins and the
factors responsible for its onset.