In genomics and related disciplines, noncoding DNA sequences are components of an organism's DNA that do not encode protein sequences. Some noncoding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, ribosomal RNA, and regulatory RNAs). Other functions of noncoding DNA include the transcriptional and translational regulation of protein-coding sequences, scaffold attachment regions, origins of DNA replication, centromeres and telomeres.
The amount of noncoding DNA varies greatly among species. For example, over 98% of the human genome is noncoding,[2] while 20% of a typical prokaryote genome is noncoding.[3] When there is much non-coding DNA, a large proportion appears to have no biological function for the organism, as theoretically predicted in the 1960s. Since that time, this non-functional portion has often been referred to as "junk DNA", a term that has elicited strong responses over the years.[4]
The international Encyclopedia of DNA Elements (ENCODE) project uncovered, by direct biochemical approaches, that at least 80% of human genomic DNA has biochemical activity.[5] Though this was not necessarily unexpected due to previous decades of research discovering many functional noncoding regions,[3][6] some scientists criticized the conclusion for conflating biochemical activity with biological function.[7][8][9][10][11] Estimates for the biologically functional fraction of our genome based on comparative genomics range between 8 and 15%.[12][13][14] However, others have argued against relying solely on estimates from comparative genomics due to its limited scope and also because non-coding DNA has been found to be involved in epigenetic activity and making the complexity of species.[6][13][15][16]
The amount of total genomic DNA varies widely between organisms, and the proportion of coding and noncoding DNA within these genomes varies greatly as well. More than 98% of the human genome does not encode protein sequences, including most sequences within introns and most intergenic DNA.[2] 20% of a typical prokaryote genome is noncoding.[3]
While overall genome size, and by extension the amount of noncoding DNA, are correlated to organism complexity, there are many exceptions. For example, the genome of the unicellular Polychaos dubium (formerly known as Amoeba dubia) has been reported to contain more than 200 times the amount of DNA in humans.[17] The pufferfish Takifugu rubripes genome is only about one eighth the size of the human genome, yet seems to have a comparable number of genes; approximately 90% of the Takifugu genome is noncoding DNA.[2] The extensive variation in nuclear genome size among eukaryotic species is known as the C-value enigma or C-value paradox.[18] Most of the genome size difference appears to lie in the noncoding DNA.
In 2013, a new "record" for the most efficient eukaryotic genome was discovered with Utricularia gibba, a bladderwort plant that has only 3% noncoding DNA and 97% of coding DNA. Parts of the noncoding DNA were being deleted by the plant and this suggested that noncoding DNA may not be as critical for plants, even though noncoding DNA is useful for humans.[1] Other studies on plants have discovered crucial functions in portions noncoding DNA that were previously thought to be negligible and have added a new layer to the understanding of gene regulation.[19]
Noncoding RNAs are functional RNA molecules that are not translated into protein. Examples of noncoding RNA include ribosomal RNA, transfer RNA, Piwi-interacting RNA and microRNA.
MicroRNAs are predicted to control the translational activity of approximately 30% of all protein-coding genes in mammals and may be vital components in the progression or treatment of various diseases including cancer, cardiovascular disease, and the immune system response to infection.[20]
Cis-regulatory elements are sequences that control the transcription of a nearby gene. Cis-elements may be located in 5' or 3' untranslated regions or within introns. Trans-regulatory elements control the transcription of a distant gene.
Promoters facilitate the transcription of a particular gene and are typically upstream of the coding region. Enhancer sequences may also exert very distant effects on the transcription levels of genes.[21]
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