lecture4_HUMAN GENOME (2015)Apunte Inglés
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Molecular biology – lecture 4
HUMAN GENOME: COMLEXITY AND DYNAMICS
1. GENES AND DNA
A gene is a segment of NDA that i sable to produce a polypeptide under regulated conditions.
These genes are not placed in specific positions of the chromosomes. In gene we can find: a) Regulatory sequences b) The transcriptional unit: the region that is going to be transcripted into RNA, this region is formed by exons and introns 2. DEFINITIONS Locus: place in chromosome. Loci in plural Diploid: 2n chromosomes. Human cells are diploid except egg and sperm cells Alleles: different variants of a gene o Homozygote: when both copies contain the same allele o Heterozygote: when the two copies contain different alleles.
Genome size varies between different species. It is usual that the more evolver an organism is, the larger the size of its genome (exception: plants and amphibious). The gene number between species also is bigger in more evolved organisms. Bacteria had simplified their genomes in order to proliferate quickly.
Although our genome is 1000 times larger than bacteria, our genome has only 10 times more genes than these.
Molecular biology – lecture 4 3. REPETITIVE DNA SEQUENCES Repetitive DNA sequences are tandem repeated sequences over and over again. We can’t find this DNA in bacteria, but in humans we can find it in: - - Highly repetitive: o Telomeric sequences (AGGGTT repeat unit in human). Telomeres in human are fromed by AGGGTT repeats and they may adopt a quadruple helical conformation due to special pairing interactions between guanines in the single stranded terminal tails o Centromeric sequences (satellite DNA) o Variable number tandem repeats (VNTRs, minisatellite DNA) VNTRs are routinely used genetic identification o Di-and nucleotide repeats (microsatellite DNA) Moderately repetitive (interspersed sequences) o Non-adjacent repeats of modules with diverse sizes dispersed between and within genes (likely originated from retrotransposons) Genes and highly repetitive NDA display different condensation degrees in the interphasic nucleus: euchromatin and heterochromatin.
Silver grains: places of the nucleus that are producing RNA, due to oxidation of silver in the microscope Molecular biology – lecture 4 4. DNA PROCESSES 4.1. Homologous recombination Homologous recombination is a genetic exchange that takes place between a pair of homologous DNA sequences.
Homologous NDA sequences are DNA sequences which are similar or identical in nucleotide sequence. It is used to repair doublestranded breaks and to exchange bits of genetic information between two different chromatids to create new combinations of DNA sequences in each chromosome during meiosis.
There is an enzyme that ensures that two chromosomes are perfectly lined.
4.2. Transposition Is the process in which a wide variety of specialized DNA (mobile genetic elements) is moved from one position in a genome, to another.
This mobile genetic elements that move by way of transposition are called transposons and they move thanks to an enzyme called transposase. This enzyme acts on a specific DNA sequence at each and of transposon causing it to insert into a new target DNA site.
Transposition has a key role in the life cycle of many viruses (basically retroviruses) and also it is considered a cause of mutation.
Molecular biology – lecture 4 4.3. Mutation Is any change in DNA, many of them being random errors that occur during replication.
Mutations can be caused by: o Tautomerism in nitrogen bases: a spontaneous mutation inherent to the DNA chemistry. It can cause the wrong incorporation of a base pair during replication that will become a fixed mutation in the following generations if not repaired.
o o o Deamination Replication errors External chemical and physical agents such as oxidation of UV light Mutations are also caused by external chemical (alkylation by tobacco, nitrosamines, depuration by oxidative radicals…) and physical (UV, X-Ray, radioactivity…) factors Depending on the altered sequence of DNA we can find: o Point mutations, caused by: Transitions: a nucleotide change of one nitrogen bas for the same type of nitrogen base Trasnversions: a nucleotide change of one nitrogen base for a different type of nitrogen base Molecular biology – lecture 4 o o o Insertions: inserting an extra nucleotide Deletions: deleting a nucleotide Translocations: move a nitrogen base from one place to another Repair: there are mechanisms that allow DNA to be repaired before mutations become stable. Mutations can cause different structural distortions into DNA (such as mutations created by UV light). The repair mechanisms the only thing they do is to look to these distortions on DNA. They look on places where the double helix has a defect. Different kind of lesions will be detected in different ways and will have different ways of getting repaired.
Once detected, mutations are repaired by a mechanism quiet general for all mutations. First, when one base can’t fit with the pair one, it creates a distortion on the hydrogen bonds. An exonuclease cuts the fragment in which there is the error and removes it. This creates a gap and the fragment will be repaired by the DNA polymerase as if it was an Okazaki fragment and the ligase will close it. There is one particular case: cytosine deamination into uracil. Cytosine can be oxidized and become a uracil. This explains why DNA has thymine instead of cytosine. If NDA had uracil and one cytosine converts into a uracil it will be impossible for the cell to detect which uracil is wrong There is a mutation that prevents the complex from detecting the thymine dimers. If both parents have damaged gens for the protein that detects this dimer, their following generations may have skin cancer very easily. This skin cancer is called xeroderma pigmentosum. This fact underlines very clearly the importance of our systems to correct errors on DNA. This means that in all of us if we take some sun we require these proteins to remove the errors of our DNA, removing thymine dimers and thus decreasing the risk of skin cancer.
We have proteins that find DNA sites that have a wrong structure and tell other proteins to cut the region that is affected. It only cuts one of the strands, and so how does the sell know whether to cut on strand or the other one? We have some enzymes (common on bacteria) that recognize specific sequences and add methyl groups to some bases. This methyl group does not affect the base (it’s not going to cause any mutation). These methyl groups are going to be added to the same base in the other strand. The enzymes that look for these sequences are slow, so during some time after replication only one strand (the parental) is methylated and which is not, and they cut the strand that doesn´t have methyl groups, in other words, the newer one.
Molecular biology – lecture 4 ...