types of mutations and the sources: translation- lecture 3 Flashcards
how can just 4 bases encode 20 amino acids
A triplet code would be the smallest set of four bases capable of encoding all 20 amino acids. In other terms, it is a specific set of three consecutive nucleotides that functions as a part of the genetic code and specifies a certain amino acid in a protein or initiates or terminates protein synthesis
you lose the frame if you remove one or two, but if you remove 3 or add 3 the frame is preserved so it works in 3 amino acids
the genetic code for rna is made of amino acids, and each triplet is called a
codon (64 codons)
1- there are stop codons
2) there are differing levels of redundancy, ranging from 6 (serine) to 1 (methionine)
-most redundancy found in third position of the codon
nirenberg used what for his experiement
poly u
transfer rna
a small RNA molecule that plays a key role in protein synthesis. Transfer RNA serves as a link (or adaptor) between the messenger RNA (mRNA) molecule and the growing chain of amino acids that make up a protein
transfer RNA (tRNA), small molecule in cells that carries amino acids to organelles called ribosomes, where they are linked into proteins
structure: molecules are composed of one short chain of RNA, 70-90 nucleotides in length, folded into a trefoil shape
how does trna work
ribosome
A ribosome is an intercellular structure made of both RNA and protein, and it is the site of protein synthesis in the cell. The ribosome reads the messenger RNA (mRNA) sequence and translates that genetic code into a specified string of amino acids, which grow into long chains that fold to form proteins
start codon
aug-methionine
initiation of translation in eukaryotes is at the blank prime cap
5’
explain how translation works
are mrna and amino acids to protein 1 to 1 ratio (as in, you can make multiple proteins from one mrna)
no, you can make multiple protein molecules from the same mrna
single nucleotide polymorphism (snips)
A DNA sequence variation that occurs when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered and the particular alteration is present in at least 1% of the population
which mutations are passed on to the next generation and which ones arent
germ cell mutations are passed on to the next generation while somatic cell mutations arent
what are somatic cells
somatic cells are any cell of a living organism other than the reproductive cells
mutations occurring in somatic cells arent passed on to the next generation (affect the body in which they occur but dont pass on)
mutations in germline cells (cell that generate gametes) are passed on
gamete
a mature male or female germ cell usually possessing a haploid chromosome set and capable of initiating formation of a new diploid individual by fusion with a gamete of the opposite sex
unfertilized reproductive cells (one from each parent, Each of those gametes had 23 chromosomes, so that after the union of those gametes, when you were just a single cell, you had 46 chromosomes. Or, 23 pairs of chromosomes)
zygote
fertilized egg cell that results from the union of a female gamete (egg, or ovum) with a male gamete (sperm). In the embryonic development of humans and other animals, the zygote stage is brief and is followed by cleavage, when the single cell becomes subdivided into smaller cells
why are somatic mutations bad
they dont contribute to future generations but they can be problematic
cancer is caused by the loss of proper cell cycle regulation and may be caused by the accumulation of mutations affecting a few key genes
Somatic & Germline Mutations
Germline mutations are changes to your DNA that you inherit from the egg and sperm cells during conception. Somatic mutations are changes to your DNA that happen after conception to cells other than the egg and sperm
A known mutation causing cystic fibrosis
cystic fibrosis, deletion of amino acid phe (need that amino acid to make sure the molecule is stable enough to leave and get translated, so protein is unstable and degrades before reaching membrane)
nucleotide substitution that creates a stop codon
nonsense mutation (truncated protein)
nucleotide substitution that doesnt change the amino acid
a synonymous mutation, or silent mutation
nucleotide substitution that changes the protein
a nonsynonymous mutation, or missense mutation
example of nucleotide substitution in public health
major type of dna damage
uv light thymine dimers
Cyclobuthane thymine dimer is a photolesion produced by UV radiation in sunlight and is considered as a potential factor causing skin cancer. It is formed as a covalently bonded complex of two adjacent thymines on a single strand of DNA.
UV radiation is limited in its effect in two ways. First,
it cannot pass through our skin, so that it can only cause mutations in cells that are directly exposed to the sun. This is why sun exposure is known to
increase an individual’s risk of developing skin cancer, but not stomach cancer. In addition, UV radiation can cause a very specific type of DNA damage, which is a covalent bond between two adjacent pyrimidine
bases (such as TT, for example). If left unrepaired, this DNA damage can cause errors during DNA replication, leading to changes at the level of one or two base pairs.
way to repair dna
another major type of dna damage
ionizing radiation
third major type of dna damage
chromosomal rearrangements
4th major type of dna damage
chemical mutagens like mustard gas
chromosomes
a threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes
Normally, each cell in the human body has 23 pairs of chromosomes (46 total chromosomes). Half come from the mother; the other half come from the father. Two of the chromosomes (the X and the Y chromosome) determine your sex as male or female when you are born.
how do we measure mutation
ames test: a biological assay to assess the mutagenic potential of chemical compounds. It utilizes bacteria to test whether a given chemical can cause mutations in the DNA of the test organism
purines
larger nucleotides with 2 ring structure, adenine and guanine
pyrimidines
smaller nucleotides with only one ring: thymine and cytosine (in rna, cytosine and uracil)
depurination
loss of purine a or g component of nucleotides, happens spontaneously and may result in mutation (more common than losing pyrimidines)
transposable elements
little pieces of dna in genomes that are capable of moving around/copying themselves in genome
At one end of tRNA is the
anti- codon, the three nucleotides that undergo pairing with the corresponding codon in the mRNA
an enzyme called () connects specific amino acids
to their appropriate tRNA molecule, via a covalent bond. Most organisms have one () for each amino acid.
aminoacyl tRNA synthetase
tRNA not bound to an amino acid is an () and one that is bound to an amino acid is a ().
uncharged tRNA
charged tRNA
During translation initiation in eukaryotes…
initiation factors, a special “initiator” tRNA charged with methionine, and the small subunit of a ribosome all assemble at the 5’ cap of the mRNA. This
complex, which is called the initiation complex, scans the mRNA for an AUG start codon, moving along the mRNA from the 5’ towards the 3’ end. When this complex encounters an AUG, the initiator tRNA, which has the anticodon 5’-CAU-3’, can base pair with it. This sets the start site for translation. Note that even though AUG is the first codon to be translated, it is not typically the first codon in the mRNA: there is a preceding region of mRNA that is not translated. Once the initiation complex has established the connection to the AUG codon, the large subunit of the ribosome joins.
The polypeptide is synthesized from the amino end to the carboxyl end, meaning that methionine will be the amino acid at the amino end of the polypeptide. Note that the AUG codon is critical for the establishment of
the proper reading frame
the initial methionine tRNA is located in the
central peptidyl site (P-site)
3 sites of ribosome
p site, then a site, then e site (exit, last one)
mutations that occur during normal biological processes such as DNA replication or cell division are considered
spontaneous
ionizing radiation
In contrast to UV radiation, ionizing radiation can penetrate deeply into tissues, and so causes mutations throughout the body, instead of only in the skin. It can cause DNA damage in a variety of ways, including
damaging bases and causing breaks in the sugar-phosphate backbone. Damaged bases can misspair, causing small-scale gene mutations, while
double-stranded breaks can fragment chromosomes, causing chromosomal mutations. When the chromosome fragments are put back together, a number of different chromosomal rearrangements can occur. These include small- and large-scale deletions and duplications, inversions, insertions, and translocations that can affect hundreds or even thousands of genes
chemical agents
Like those caused by ionizing radiation, mutations caused by chemical agents can affect all cells in the body. This is because chemical agents can circulate in the blood and lymph, so that all cells, including
both somatic and germ cells, are exposed. However, unlike ionizing radiation, chemical agents are generally limited to causing smaller-scale gene mutations, because they affect individual bases.
alkylating agents
These chemicals add bulky hydrocarbon groups to DNA bases, affecting their ability to base-pair. One type of alkylating agent is mustard gas, which was used during World War I. Exposure to this mutagen causes such
severe DNA damage that cells of affected individuals die, causing blistering, bleeding, and other tissue damage. Survivors are also at an increased risk of developing cancer. Alkylating agents are used by
scientists to induce mutations in experimental organisms (because, as noted above, it’s possible to derive information about the function of a
gene by disrupting that function mutationally). For example, ethylmethylsulfonate (EMS) changes guanine to produce a modified nucleotide which pairs with thymine. Thus, EMS produces C * G → T * A changes
Mutations may result from spontaneous chemical changes in DNA. One such change is depurination:
the loss of a purine base [i.e., an A or a
G] from a nucleotide. Depurination results when the covalent bond connecting the purine to the deoxyribose sugar breaks, producing an
apurinic site, a nucleotide that lacks its purine base. An apurinic site cannot act as a template for a complementary base in replication. In the
absence of base-pairing constraints, an incorrect nucleotide (usually adenine) is incorporated into the newly synthesized DNA strand opposite
the apurinic site. Pyrimidines are less prone to this kind of spontaneous decay
Biological agents such as transposons (transposable elements) can cause mutations. Transposons are
mobile genetic elements that can either copy and paste themselves into new sites in the genome or cut
themselves out of their current location and insert into a new one. They were first discovered by Barbara McClintock in her studies of the pigmentation of corn kernels. When transposons insert themselves, they
can disrupt the coding or regulatory sequences of genes, which can interfere with their functions. An example of the mutagenic effect of transposable elements is seen in the color of grapes. Black and red grapes result from the production of red pigments, called anthocyanins, which are lacking in white grapes. White grapes resulted from a mutation
caused by the insertion of a transposable element into the anthocyanin-producing gene in black grapes that turned off the production of anthocyanins. Red grapes resulted from a second mutation that occurred
in white grapes removing most, but not all, of the transposon. This switched anthocyanin production back on, but not as intensely as in the original black grapes. In other cases, transposons insert into noncoding regions and do not cause any phenotypic consequences. Genomes bear testimony to past bouts of transposon activity: around 10% of the
human genome consists of copies of a particular element, Alu, which is no longer actively undergoing transposition, but which was clearly highly
active in the past.
