Molecular Biology Terms Starting With W
Molecular Biology Glossary: W
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Watson-Crick Base Pairing
/ WOT-sun KRIK BAYS PAIR-ing / · Named after James Watson and Francis Crick (1953)
Watson-Crick Base Pairing is the specific hydrogen bonding between complementary nucleotide bases in nucleic acids, with adenine pairing with thymine in DNA and with uracil in RNA, and guanine pairing with cytosine in both.
James Watson and Francis Crick deduced these pairing rules in 1953 using X-ray diffraction data collected by Rosalind Franklin and Maurice Wilkins, and the geometry of the pairs explained why Erwin Chargaff had measured equal molar amounts of adenine and thymine and of guanine and cytosine in DNA from many species. Adenine-thymine pairs are held by two hydrogen bonds, while guanine-cytosine pairs form three, making GC-rich regions of DNA more thermally stable. Genomic regions with GC content above 60 percent typically require temperatures above 95 degrees Celsius to fully separate the two strands, a property researchers exploit to estimate GC content from DNA melting curves.
This strict complementarity also underlies DNA replication, transcription, and the hybridization of synthetic probes to target sequences.
Certain thermophilic archaea, including Sulfolobus acidocaldarius, live in hot springs at temperatures exceeding 80 degrees Celsius. Their genomes are not unusually GC-rich; instead, these organisms use specialized proteins called chromatin-associated proteins to stabilize their DNA, revealing that Watson-Crick base pairing alone is insufficient to maintain double-stranded DNA at extreme temperatures.
Building Blocks of Nucleic Acids →Any base can pair with any other base as long as the two strands are antiparallel. Base shape and hydrogen-bonding geometry strongly favor specific pairs: adenine and guanine are purines with two-ring structures, while thymine and cytosine are pyrimidines with one-ring structures, and only purine-pyrimidine pairings maintain the uniform 2-nanometer width of the double helix.
DNA probes used in fluorescence in situ hybridization bind their chromosomal targets through Watson-Crick base pairing. A typical FISH probe is 100 to 500 kilobases long and must share at least 90 percent sequence identity with its target to form a stable hybrid under standard hybridization conditions of 37 degrees Celsius and 50 percent formamide.
Whole Exome Sequencing
/ HOHL EK-sohm SEE-kwen-sing / · From Old English hal, entire, Greek exo, outside, and Latin sequentia, following in order.
Whole Exome Sequencing is a genomic technique that selectively captures and sequences all protein-coding exons in a genome, covering approximately 1 to 2 percent of total genomic DNA while targeting the regions where most known disease-causing mutations occur.
Whole exome sequencing targets roughly 180,000 exons comprising about 30 million base pairs of the human genome, where approximately 85 percent of known disease-causing mutations reside. Biotinylated RNA or DNA probes complementary to exonic sequences hybridize to fragmented genomic DNA, pulling down exon-containing fragments before high-throughput sequencing. Coverage depth typically ranges from 50x to 100x, ensuring reliable variant detection with sensitivity exceeding 95 percent for single nucleotide variants, though structural rearrangements and non-coding regulatory mutations escape detection.
Compared to whole genome sequencing, the technique costs significantly less while maintaining high diagnostic yield for Mendelian disorders, and it achieved its first major clinical success in 2009 when researchers used it to identify the causative gene for Miller syndrome.
Each person carries an average of 100 to 400 loss-of-function variants in which both copies of a gene are disrupted, a finding that emerged from large-scale whole exome sequencing studies of healthy individuals. Most carriers of these variants show no symptoms, a pattern that has reshaped understanding of how much functional redundancy exists in the human genome.
Whole exome sequencing captures all disease-causing mutations. Variants in non-coding regulatory regions, deep intronic mutations that disrupt splicing, and large structural rearrangements are not efficiently detected by standard whole exome sequencing pipelines, meaning a negative result does not rule out a genetic cause.
At the NIH Undiagnosed Diseases Program, whole exome sequencing of patient-parent trios has resolved approximately 35 percent of cases that resisted diagnosis for years. Trio sequencing compares the patient's exome to both parents' exomes simultaneously, allowing de novo mutations to be identified with far greater confidence than single-sample analysis; this approach identified NGLY1 deficiency, a previously unknown disorder of glycoprotein degradation, in 2012.
Wobble Hypothesis
/ WOB-ul hy-POTH-eh-sis / · Old English wabian (to waver) + Greek hypothesis (supposition)
Wobble Hypothesis is Francis Crick's 1966 proposal that the third position of a codon permits non-standard base pairing with the first position of the tRNA anticodon, explaining how fewer than 61 tRNA species can decode all sense codons.
This flexibility means a single tRNA can recognize two or more synonymous codons, reducing the total number of tRNA species required for complete translation of the genetic code. Inosine, a modified nucleoside found at the wobble position of many tRNAs, can pair with U, C, or A, providing the broadest decoding range of any single anticodon nucleotide. Crick’s original proposal correctly predicted that the anticodon first position would tolerate unusual base pairs, a prediction confirmed when inosine-containing tRNAs were characterized biochemically in the years following his 1966 paper.
Humans encode only about 45 distinct cytoplasmic tRNA genes yet translate all 61 sense codons, a compression made possible entirely by wobble pairing.
The bacterium Mycoplasma capricolum has one of the smallest known tRNA complements, using just 29 tRNA species to decode its entire genome, a number far below 61 because wobble pairing and codon bias together allow extreme economy in translation machinery.
Every codon requires a completely unique tRNA. Wobble pairing at the third codon position lets some tRNAs recognize multiple codons differing only at that position.
In the yeast Saccharomyces cerevisiae, a single tRNA carrying inosine at the wobble position of its anticodon decodes three synonymous codons for threonine: ACU, ACC, and ACA. Genome-wide tRNA surveys show that yeast manages translation of all 61 sense codons with approximately 42 cytoplasmic tRNA species, demonstrating the quantitative impact of wobble flexibility on cellular economy.