Molecular Biology Terms Starting With J
Molecular Biology Glossary: J
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Junction Sequence
/ JUNK-shun SEE-kwens / · Latin: junctio (joining) + sequentia
Junction Sequence is a DNA or RNA segment at the boundary where two distinct genomic regions meet, such as the border between an exon and an intron or between a viral insert and host chromosomal DNA.
Splice junction sequences carry conserved dinucleotides at exon-intron boundaries: the 5-prime splice site begins with GU in roughly 99.5 percent of human introns, and the 3-prime splice site ends with AG in approximately 99.8 percent. Single-nucleotide changes at these positions disrupt binding by U1 small nuclear RNA at the 5-prime site or by the splicing factor U2AF65 at the 3-prime site, dropping splicing efficiency from near 100 percent to as low as 10 percent and causing exon skipping or activation of cryptic splice sites. Recombination signal sequences flanking V, D, and J gene segments are recognized by the RAG1 and RAG2 recombinase with single-nucleotide precision, and the junctions produced by VDJ recombination generate the diversity of antibody and T-cell receptor sequences.
Retroviral integration creates a distinct class of junction: HIV-1 inserts its proviral DNA with target-site duplications of exactly 5 base pairs flanking each end of the integrated sequence, a signature detectable by junction-spanning PCR. Engineered junctions introduced during molecular cloning often contain restriction enzyme recognition sites that allow the insert to be excised and verified by diagnostic digestion.
The junction sequences produced by VDJ recombination in developing B cells are not encoded in the germline genome. Random nucleotide additions by the enzyme terminal deoxynucleotidyl transferase at each junction point generate up to 10 to the 15th power distinct antibody sequences from fewer than 200 gene segments, a combinatorial diversity that exceeds the number of B cells in the human body.
Building Blocks of Nucleic Acids →Joined DNA or RNA segments have no detectable boundary. Junction sequences are often the most diagnostically informative regions of a genome, detectable by sequencing or junction-spanning PCR even when the flanking sequences are identical to normal.
In patients with chronic myelogenous leukemia, the BCR-ABL fusion gene produces a junction sequence at the chromosomal breakpoint where chromosome 9 and chromosome 22 exchange segments. Reverse-transcription PCR primers that span this junction amplify a product of approximately 200 to 300 base pairs from patient RNA, and the assay can detect one leukemic cell among 100,000 normal cells during treatment monitoring.
Junk DNA
/ JUNK DEE-EN-AY / · From Middle English jonk, old rope, and DNA, deoxyribonucleic acid from deoxyribose and nucleic acid.
Junk DNA is a colloquial term for genomic sequences that do not encode proteins and were historically assumed to have no function, though subsequent research has identified regulatory and structural roles for many such sequences.
The term entered scientific discourse in the 1960s after researchers discovered that more than 98 percent of the human genome does not code for proteins, prompting Susumu Ohno to coin the phrase “junk DNA” in a 1972 paper. Subsequent work revealed that large portions of this non-coding DNA contain enhancers, silencers, insulators, and genes encoding functional non-coding RNAs such as microRNAs and long non-coding RNAs. Transposable elements alone account for roughly 45 percent of the human genome; while most are transcriptionally silenced, some have been co-opted as regulatory elements or exon sequences over evolutionary time.
The ENCODE consortium reported in 2012 that approximately 80 percent of the human genome shows some biochemical activity, though population geneticists have argued that only 8 to 15 percent shows evidence of purifying selection consistent with biological function. This gap between biochemical activity and evolutionary constraint remains an active area of debate, with estimates of truly functional non-coding sequence varying widely among research groups.
The pufferfish Takifugu rubripes carries roughly the same number of protein-coding genes as humans, approximately 20,000, but its genome is only about 400 million base pairs long, compared to the human genome's 3.2 billion. Comparative genomic studies show that conserved non-coding sequences shared between pufferfish and humans are far more likely to function as regulatory elements than sequences present only in mammals, providing an evolutionary filter for distinguishing functional from non-functional non-coding DNA.
All non-coding DNA has hidden functions waiting to be discovered. Population genetic analyses show that large fractions of non-coding sequence accumulate mutations at rates indistinguishable from neutral drift, indicating that these regions are not under selective pressure to maintain a specific sequence.
In maize (Zea mays), transposable elements make up roughly 85 percent of the genome and have expanded the total genome size to approximately 2.4 billion base pairs, compared to about 135 million base pairs in the related grass sorghum (Sorghum bicolor). Barbara McClintock first identified these mobile elements in maize in the 1940s, work that earned her the Nobel Prize in Physiology or Medicine in 1983.