User:GnaeusMuciusMarius/New sandbox

Ribosomal DNA (rDNA) is a DNA sequence that codes for ribosomal RNA. Ribosomes are assemblies of proteins and rRNA molecules that translate mRNA molecules to produce proteins. As shown in the figure, rDNA of eukaryotes consists of a tandem repeat of a unit segment, an operon, composed of NTS, ETS, 18S, ITS1, 5.8S, ITS2, and 28S tracts. rDNA has another gene, coding for 5S rRNA, located in the genome in most eukaryotes. 5S rDNA is also present in tandem repeats as in Drosophila. In the nucleus, the rDNA region of the chromosome is visualized as a nucleolus which forms expanded chromosomal loops with rDNA. These rDNA regions are also called nucleolus organizer regions, as they give rise to the nucleolus. In the human genome there are 5 chromosomes with nucleolus organizer regions: the acrocentric chromosomes 13 (RNR1), 14 (RNR2), 15 (RNR3), 21 (RNR4) and 22 (RNR5). In Bacteria, Archaea, and chloroplasts the rRNA is composed of different (smaller) units, the large (23S) ribosomal RNA, 16S ribosomal RNA and 5S rRNA. The 16S rRNA is widely used for phylogenetic studies.

Sequence homogeneity of the repeat unit
In the large rDNA array, polymorphisms between rDNA repeat units are very low, indicating that rDNA tandem arrays are evolving through concerted evolution. However, the mechanism of concerted evolution is imperfect, such that polymorphisms between repeats within an individual can occur at significant levels and may confound phylogenetic analyses for closely related organisms.

5S tandem repeat sequences in several Drosophila were compared with each other; the result revealed that insertions and deletions occurred frequently between species and often flanked by conserved sequences. They could occur by slippage of the newly synthesized strand during DNA replication or by gene conversion.

Sequence divergence to clarify phylogeny
The rDNA transcription tracts have low rate of polymorphism among species, which allows interspecific comparison to elucidate phylogenetic relationship using only a few specimens. Coding regions of rDNA are highly conserved among species but ITS regions are variable due to insertions, deletions, and point mutations. Between remote species as human and frog comparison of sequences at ITS tracts is not appropriate. Conserved sequences at coding regions of rDNA allow comparisons of remote species, even between yeast and human. Human 5.8S rRNA has 75% identity with yeast 5.8S rRNA. In cases for sibling species, comparison of the rDNA segment including ITS tracts among species and phylogenetic analysis are made satisfactorily. The different coding regions of the rDNA repeats usually show distinct evolutionary rates. As a result, this DNA can provide phylogenetic information of species belonging to wide systematic levels.

Recombination-stimulating activity
A fragment of yeast rDNA containing the 5S gene, nontranscribed spacer DNA, and part of the 35S gene has localized cis-acting mitotic recombination stimulating activity. This DNA fragment contains a mitotic recombination hotspot, referred to as HOT1. HOT1 expresses recombination-stimulating activity when it is inserted into novel locations in the yeast genome. HOT1 includes an RNA polymerase I (PolI) transcription promoter that catalyzes 35S ribosomal rRNA gene transcription. In a PolI defective mutant, the HOT1 hotspot recombination-stimulating activity is abolished.The level of PolI transcription in HOT1 appears to determine the level of recombination.

DNA regions that are repetitive often undergo recombination events. The rDNA repeats have many regulatory mechanisms that keep the DNA from undergoing mutations, thus keeping the rDNA conserved. In rDNA, the tandem repeats are largely found in the nucleolus; but heterochromatic rDNA is found near the nucleolus. However, the rDNA that is transcriptionally active is found within the nucleolus itself. The genes that are responsible for encoding the various sub-units of rRNA are located across multiple chromosomes in humans. But, the genes that encode for rRNA are highly conserved across the domains, with only the copy numbers involved for the genes having varying numbers per species.

Human diseases that are associated with Ribosomal DNA repeat mutations

Diseases can be associated with DNA mutations where DNA can be be expanded, like in Huntington's disease, or lost due to deletion mutations. The same is true for mutations that occur in rDNA repeats, it has been found that if genes that are associated with ribosome synthesis are disrupted or mutated, it can result in diseases associated with the skeleton or bone marrow. Also, any damage or disruption to the enzymes that protect the tandem repeats of the rDNA can result in lower synthesis of ribosomes, which also lead to other defects in the cell. Neurological diseases can also arise from mutations in the rDNA tandem repeats, such as Bloom syndrome, which occurs when the number of tandem repeats increases close to 100 fold, compared to that of a normal number of the repeats. Various types of cancers can also be born from mutations of the tandem repeats of the rDNA. Cell lines can become malignant from either a rearrangement of the tandem repeats, or an expansion of the repeats in the rDNA.