Telomere
The existence of a special structure at the ends of chromosomes was independently proposed in 1938 by Hermann Joseph Muller, studying the fruit fly Drosophila melanogaster, and in 1939 by Barbara McClintock, working with maize.
[1] Muller observed that the ends of irradiated fruit fly chromosomes did not present alterations such as deletions or inversions.
He hypothesized the presence of a protective cap, which he coined "telomeres", from the Greek telos (end) and meros (part).
[3][4][5] According to his theory of marginotomy, DNA sequences at the ends of telomeres are represented by tandem repeats, which create a buffer that determines the number of divisions that a certain cell clone can undergo.
[6][7] In 1975–1977, Elizabeth Blackburn, working as a postdoctoral fellow at Yale University with Joseph G. Gall, discovered the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends.
[8] Blackburn, Carol Greider, and Jack Szostak were awarded the 2009 Nobel Prize in Physiology or Medicine for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.
[14] In many species, the sequence repeats are enriched in guanine, e.g. TTAGGG in vertebrates,[15] which allows the formation of G-quadruplexes, a special conformation of DNA involving non-Watson-Crick base pairing.
There is evidence for the 3'-overhang in ciliates (that possess telomere repeats similar to those found in vertebrates) to form such G-quadruplexes that accommodate it, rather than a T-loop.
[16] Many organisms have a ribonucleoprotein enzyme called telomerase, which carries out the task of adding repetitive nucleotide sequences to the ends of the DNA.
[18] The steady shortening of telomeres with each replication in somatic (body) cells may have a role in senescence[19] and in the prevention of cancer.
[22][23] Telomere length varies greatly between species, from approximately 300 base pairs in yeast[24] to many kilobases in humans, and usually is composed of arrays of guanine-rich, six- to eight-base-pair-long repeats.
The literature concerning telomeres as integrative biomarkers of exposure to stress and adversity is dominated by cross-sectional and correlational studies, which makes causal interpretation problematic.
[43] There is little evidence that, in humans, telomere length is a significant biomarker of normal aging with respect to important cognitive and physical abilities.
[44] Experimentally verified and predicted telomere sequence motifs from more than 9000 species are collected in research community curated database TeloBase.
[45] Some of the experimentally verified telomere nucleotide sequences are also listed in Telomerase Database website (see nucleic acid notation for letter representations).
Preliminary research indicates that disease risk in aging may be associated with telomere shortening, senescent cells, or SASP (senescence-associated secretory phenotype).
[57][58] Nobel Prize winner Elizabeth Blackburn, who was co-founder of one company, promoted the clinical utility of telomere length measures.
[63] In 2019, a meta-analysis confirmed that the exposure to stressors (e.g. pathogen infection, competition, reproductive effort and high activity level) was associated with shorter telomeres across different animal taxa.
[64] Studies on ectotherms, and other non-mammalian organisms, show that there is no single universal model of telomere erosion; rather, there is wide variation in relevant dynamics across Metazoa, and even within smaller taxonomic groups these patterns appear diverse.
