Ultra-conserved element
Encyclopedia
An ultra-conserved element is a region of human DNA
of length 200 nucleotide
s or greater, which is entirely conserved (identical nucleic acid sequence) in both rats and mice. Despite often being noncoding DNA
, some ultra-conserved elements have been found to be transcriptionally active, giving non-coding RNA
molecules.
ary importance as these regions appear to have experienced strong negative selection
for 300-400 million years. The probability of finding ultra-conserved elements by chance (under neutral evolution
) has been estimated at less than 10−22 in 2.9 billion bases.
. A small number of those which are transcribed have been connected with human carcinoma
s and leukemia
s. For example, TUC338
is strongly upregulated in human hepatocellular carcinoma
cells. A study comparing ultra-conserved elements between humans and Fugu rubripes proposed an importance in vertebrate development. Several ultra-conserved elements are located near transcriptional regulators or developmental genes.
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
of length 200 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s or greater, which is entirely conserved (identical nucleic acid sequence) in both rats and mice. Despite often being noncoding DNA
Noncoding DNA
In genetics, noncoding DNA describes components of an organism's DNA sequences that do not encode for protein sequences. In many eukaryotes, a large percentage of an organism's total genome size is noncoding DNA, although the amount of noncoding DNA, and the proportion of coding versus noncoding...
, some ultra-conserved elements have been found to be transcriptionally active, giving non-coding RNA
Non-coding RNA
A non-coding RNA is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA , non-messenger RNA and functional RNA . The term small RNA is often used for short bacterial ncRNAs...
molecules.
Evolution
Perfect conservation of these long stretches of DNA is thought to imply evolutionEvolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
ary importance as these regions appear to have experienced strong negative selection
Negative selection (natural selection)
In natural selection, negative selection or purifying selection is the selective removal of alleles that are deleterious. This can result in stabilizing selection through the purging of deleterious variations that arise....
for 300-400 million years. The probability of finding ultra-conserved elements by chance (under neutral evolution
Neutral theory of molecular evolution
The neutral theory of molecular evolution states that the vast majority of evolutionary changes at the molecular level are caused by random drift of selectively neutral mutants . The theory was introduced by Motoo Kimura in the late 1960s and early 1970s...
) has been estimated at less than 10−22 in 2.9 billion bases.
Functions
481 ultra-conserved elements have been identified in the human genomeHuman genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
. A small number of those which are transcribed have been connected with human carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...
s and leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
s. For example, TUC338
TUC338
TUC338 is an ultra-conserved element which is transcribed to give a non-coding RNA. The TUC338 gene was first identified as uc.338, along with 480 other ultra-conserved elements in the human genome...
is strongly upregulated in human hepatocellular carcinoma
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
cells. A study comparing ultra-conserved elements between humans and Fugu rubripes proposed an importance in vertebrate development. Several ultra-conserved elements are located near transcriptional regulators or developmental genes.