DNA

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This page is about DNA and interesting genomic phenomena.

Transposable Elements


A transposable element (TE) or transposon is a DNA sequence that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Many TEs contain promoters which drive transcription of their own transposase. These promoters can cause aberrant expression of linked genes, causing disease or mutant phenotypes.

Retrotransposons

Retrotransposons also called transposons via RNA intermediate are genetic elements that can amplify themselves in a genome and are ubiquitous components of the DNA of many eukaryotic organisms. These DNA sequences use a "copy-and-paste" mechanism, whereby they are first transcribed into RNA, then converted back into identical DNA sequences using reverse transcription, and these sequences are then inserted into the genome at target sites.

DNA Transposons

DNA Transposons (aka Class II elements) are a group of transposable elements that can move in the DNA of an organism via a single- or double-stranded DNA intermediate. There are autonomous, as well as nonautonomous DNA transposons. The latter use the enzymatic machinery of the former for their amplification in a genome. It is estimated, that there are around 300,000 copies of DNA transposon fossils in the human genome and they make up around 3% of it.

Alu element

An Alu element is a short stretch of DNA originally characterized by the action of the Arthrobacter luteus (Alu) restriction endonuclease.[1] Alu elements are the most abundant transposable elements, containing over one million copies dispersed throughout the human genome.[2] They are derived from the small cytoplasmic 7SL RNA, a component of the signal recognition particle.

Short Interspersed Nuclear Elements

Short Interspersed Nuclear Elements (SINEs) are non-autonomous, non-coding transposable elements (TEs) that are 50-500 base pairs long. The internal regions of SINEs originate from tRNA and remain highly conserved, suggesting positive pressure to preserve structure and function of SINEs. While SINEs are present in many species of vertebrates and invertebrates, SINEs are often lineage specific, making them useful markers of divergent evolution between species. Copy number variation and mutations in the SINE sequence make it possible to construct phylogenies based on differences in SINEs between species. SINEs are also implicated in certain types of genetic disease in humans and other eukaryotes.


Pseudogenes


Pseudogenes are segments of DNA that are related to real genes. Pseudogenes have lost at least some functionality, relative to the complete gene, in cellular gene expression or protein-coding ability. Pseudogenes often result from the accumulation of multiple mutations within a gene whose product is not required for the survival of the organism, but can also be caused by genomic copy number variation (CNV) where segments of 1+ kb are duplicated or deleted. Although not fully functional, pseudogenes may be functional, similar to other kinds of noncoding DNA, which can perform regulatory functions. The "pseudo" in "pseudogene" implies a variation in sequence relative to the parent coding gene, but does not necessarily indicate pseudo-function. Despite being non-coding, many pseudogenes have important roles in normal physiology and abnormal pathology.


CpG islands


CpG sites CpG islands typically occur at or near the transcription start site of genes, particularly housekeeping genes, in vertebrates. A C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the cytosines in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over time methylated cytosines tend to turn into thymines because of spontaneous deamination. There is a special enzyme in humans (Thymine-DNA glycosylase, or TDG) that specifically replaces T's from T/G mismatches. However, due to the rarity of CpGs, it is theorised to be insufficiently effective in preventing a possibly rapid mutation of the dinucleotides. The existence of CpG islands is usually explained by the existence of selective forces for relatively high CpG content, or low levels of methylation in that genomic area, perhaps having to do with the regulation of gene expression. Recently a study showed that most CpG islands are a result of non-selective forces.


RNA Splicing


Splicing is the editing of the nascent precursor messenger RNA (pre-mRNA) transcript into a mature messenger RNA (mRNA). After splicing, introns are removed and exons are joined together (ligated). For nuclear-encoded genes, splicing takes place within the nucleus either during or immediately after transcription. For those eukaryotic genes that contain introns, splicing is usually required in order to create an mRNA molecule that can be translated into protein. For many eukaryotic introns, splicing is carried out in a series of reactions which are catalyzed by the spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs). Self-splicing introns, or ribozymes capable of catalyzing their own excision from their parent RNA molecule, also exist.


Self-splicing introns

Self-splicing introns (aka S group I introns) are processed by two sequential ester-transfer reactions. The exogenous guanosine or guanosine nucleotide (exoG) first docks onto the active G-binding site located in P7, and its 3'-OH is aligned to attack the phosphodiester bond at the 5' splice site located in P1, resulting in a free 3'-OH group at the upstream exon and the exoG being attached to the 5' end of the intron. Then the terminal G (omega G) of the intron swaps the exoG and occupies the G-binding site to organize the second ester-transfer reaction: the 3'-OH group of the upstream exon in P1 is aligned to attack the 3' splice site in P10, leading to the ligation of the adjacent upstream and downstream exons and release of the catalytic intron. Two-metal-ion mechanism seen in protein polymerases and phosphatases was proposed to be used by group I and group II introns to process the phosphoryl transfer reactions, which was unambiguously proven by a recently resolved high-resolution structure of the Azoarcus group I intron.


tRNA splicing

tRNA (also tRNA-like) splicing is a rare form of splicing that usually occurs in tRNA. The splicing reaction involves a different biochemistry than the spliceosomal and self-splicing pathways. tRNA splicing endonuclease heterotetramer cleaves pre-tRNA at two sites in the acceptor loop to form a 5'-half tRNA, terminating at a 2',3'-cyclic phosphodiester group, and a 3'-half tRNA, terminating at a 5'-hydroxyl group, along with a discarded intron. tRNA kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. tRNA cyclic phosphodiesterase cleaves the cyclic phosphodiester group to form a 2'-phosphorylated 3' end. tRNA ligase adds an adenosine monophosphate group to the 5' end of the 3'-half and joins the two halves together. NAD-dependent 2'-phosphotransferase then removes the 2'-phosphate group.


Ribonucleoprotein

Ribonucleoprotein (RNP) is a protein-RNA complex of ribonucleic acid + (RNA-binding) protein. These complexes play an integral part in a number of important biological functions that include DNA replication, regulating gene expression and regulating the metabolism of RNA. A few examples of RNPs include the ribosome, the enzyme telomerase, vault ribonucleoproteins, RNase P, hnRNP and small nuclear RNPs (snRNPs), which have been implicated in pre-mRNA splicing (spliceosome) and are among the main components of the nucleolus.