Ikke-kodende DNA

Illustration af forholdet mellem det humane genoms forskellige komponenter

I molekylærbiologi er junk-DNA eller nonsens-DNA en forældet benævnelse for kromosomers eller genomers DNA-sekvenser, som ikke har en kendt funktion. Op imod 97 % af den menneskelige genom er blevet omtalt som "junk" – eller på dansk affald, men det afspejler nok snarere det faktum at kun 1,5% af det humane genom koder for protein, men en stor del af resten har efterhånden fået tildelt kendte funktioner (se billedet).

Selvom det meste af junk-DNA sekvenserne kunne formodes at være evolutionære rester, som ikke har noget aktuelt formål, tror nogle at junk-DNA fungerer på måder, vi endnu ikke kender betydningen af.^[1] Ydermere kan bevarelsen af noget junk-DNA over millioner af års evolution måske betyde, at det har en livsvigtig funktion. Nogle betragter mærkaten "junk" som en forkert benævnelse, mens andre anser junk-DNA som DNA gemt væk til mulig fremtidig anvendelse, i stedet for noget, der skal smides ud.

Nogle foretrækker benævnelsen ikke-kodende DNA, selvom junk-DNA ofte indeholder transposoner, der koder for proteiner uden klar funktion i deres vært. Retrotransposoner eller endogene retrovirus stammer fra retrovirus. Atter andet DNA kommer fra parasitter. Et eksempel herpå er at 70% af hvirvelløse dyr har indlejret store dele af eller næsten hele parasitten Wolbachias genom i deres genom.^[2]

Det vides nu at det humane genom indeholder omkring 100.000 stumper retrovirus-DNA kaldet endogene retrovirus, som udgør omkring 8% af genomet, men man kender kun funktionen eller betydningen af enkelte genprodukter deraf.^[3]^[4]

Videnskaben funktionel genomik har udviklet mange accepterede teknikker til at karakterisere proteinkodende gener, RNA-gener og regulerende regioner. I det meste af planter og dyrs genomer udgør det proteinkodende DNA kun en mindre procentdel. I menneskets tilfælde 1-2 %. Funktionen af resten bliver undersøgt. Meget af det kan identificeres som repeterende DNA-sekvenser uden kendt biologisk funktion for deres vært. Det er dog værdifuldt for genetikere, da de kan anvende det til nedarvningsklassifikation. Men når dette er fratrukket junk-DNA, er der stadig store mængder sekvenser, som indtil videre ikke kan klassificeres til andet end "junk".

Et organismes genomstørrelse inkl. junk-DNA ser ud til at have lille sammenhæng med organismets kompleksitet: Det er blevet rapporteret, at genomet for den encellede organisme Amoeba dubia mængdemæssigt indeholder mere end 200 gange så meget DNA som menneskets genom"^[5] ^[6].

Pindsvinefisken Takifugu rubripes genom indeholder mængdemæssigt kun 1/10 af menneskets genom, men ser ud til at have ligeså mange brugte gener som menneskets. Det meste af forskellen ser ud til at ligge i det der i dag kaldes junk-DNA.^[7]

Kritiske funktioner fundet i "ikke-kodende DNA"

I nyere tid er der i forskellige organismer blevet fundet vigtige funktioner i DNA, der tidligere var klassificeret som junk-DNA. ^[8] ^[9] ^[10] ^[11] F.eks. opdagede forskere i 2013, at hjernens udvikling guides af "junk-DNA" ^[12], og "junk-DNA" former vores ansigt.^[13]

Efter flere års forskning er det blevet afsløret i 2018, at en særlig type transposon kaldet "LINE1", der udgør mere end 20 % af menneskers genom, er kritisk for embryoudviklingen, helt fra den kun er to celler. "Slukkes" "LINE1", stopper embryoudvikling. Transposoner er en form for "junk-DNA", hvis opførsel ligner genetiske parasitter. "LINE1" er, som forskningen viser, absolut ikke en genetisk parasit, men er derimod yderst livsnødvendig.^[14]

Se også

Kilder/referencer

^ 14 June 2007, BBC News: Human genome further unravelled, backup Citat: "...it suggests genes, so called junk DNA and other elements, together weave an intricate control network...He said: "The genome looks like it is far more of a network of RNA transcripts that are all collaborating together. Some go off and make proteins; [and] quite a few, although we know they are there, we really do not have a good understanding of what they do. "This leads to a much more complex picture." The researchers now hope to scale up their efforts to look at the other 99% of the genome..."
^ University of Rochester (2007, August 31). One Species' Entire Genome Discovered Inside Another's. ScienceDaily. Retrieved November 10, 2007, backup Citat: "..."This study establishes the widespread occurrence and high frequency of a process that we would have dismissed as science fiction until just a few years ago," says W. Ford Doolittle, Canada Research Chair in Comparative Microbial Genomics at Dalhousie University, who is not connected to the study. "This is stunning evidence for increased frequency of gene transfer."..."This parasite has implanted itself inside the cells of 70 percent of the world's invertebrates, coevolving with them. And now, we've found at least one species where the parasite's entire or nearly entire genome has been absorbed and integrated into the host's. The host's genes actually hold the coding information for a completely separate species."..."
^ Mammals Carry a Graveyard of Viruses in Our DNA, And It Could Have a Crucial Purpose. ScienceAlert 2021, backup
^ Ancient Viruses Are Buried in Your DNA. NYTimes Science 2017, backup
^ Gregory, T.R. and P.D.N. Hebert . (1999). "The modulation of DNA content: proximate causes and ultimate consequences". Genome Research. 9: 317-324.
^ Gregory, T.R. (2005). Animal Genome Size Database. http://www.genomesize.com .
^ Wahls, W.P.; et al. (1990). "Hypervariable minisatellite DNA is a hotspot for homologous recombination in human cells". Cell. 60 (1): 95-103. PMID 2295091. {{cite journal}}: Eksplicit brug af et al. i: |author= (hjælp)
^ 12 May, 2004, BBC News: 'Junk' throws up precious secret, backup Citat: "..."It is very lucky that entire genomes were mapped, as this work is showing." He added: "I think other bits of 'junk' DNA will turn out not to be junk. I think this is the tip of the iceberg, and that there will be many more similar findings."..."
^ 2005-07-12, Sciencedaily: Rodent Social Behavior Encoded In Junk DNA, backup Citat: "..."It was considered junk DNA because it didn't seem to have any function," noted Hammock..."
^ Paywalled: October 2004, Scientific american: The Hidden Genetic Program of Complex Organisms, tidligere link, backup Citat: "...But an overlooked regulatory system based on RNA may hold the keys to development and evolution..."
^ April 24, 2007, Sciencedaily: 'Junk' DNA Now Looks Like Powerful Regulator, Scientists Find, backup Citat: "...Many of those snippets were located in gene-free chromosomal expanses once described by geneticists as "gene deserts." These sections are, in fact, so clogged with useful DNA bits – including the ones Bejerano and his colleagues describe – that they've been renamed "regulatory jungles."...transposons that duplicate themselves and hop around the genome. "We used to think they were mostly messing things up. Here is a case where they are actually useful," Bejerano said..."Now we've shown that transposons may be a major vehicle for evolutionary novelty," he said...."
^ University of California, San Francisco (UCSF) (2013, April 15). Brain development is guided by junk DNA that isn't really junk. ScienceDaily, backup
^ 25. oktober 2013, videnskab.dk: Vores ansigter formes af 'overflødigt' DNA, backup
^ University of California - San Francisco. (2018, June 21). Not junk: 'Jumping gene' is critical for early embryo: Gene that makes up a fifth of the human genome is not a parasite, but key to the first stages of embryonic development. ScienceDaily, backup Citat: "...Only about 1 percent of the human genome encodes proteins, and researchers have long debated what the other 99 percent is good for...For example, fully half of our DNA is made up of "transposable elements," or "transposons," virus-like genetic material that has the special ability of duplicating and reinserting itself in different locations in the genome, which has led researchers to dub them genetic parasites...Now UCSF scientists have revealed that, far from being a freeloader or parasite, the most common transposon, called LINE1, which accounts for 20 percent or more of the human genome, is actually necessary for embryos to develop past the two-cell stage...The team tried eliminating LINE1 from fertilized eggs and found that the embryos completely lost their ability to progress past the two-cell phase..."We now think these early embryos are playing with fire but in a very calculated way," Ramalho-Santos said. "This could be a very robust mechanism for regulating development."..."

[1] 14 June 2007, BBC News: Human genome further unravelled, backup Citat: "...it suggests genes, so called junk DNA and other elements, together weave an intricate control network...He said: "The genome looks like it is far more of a network of RNA transcripts that are all collaborating together. Some go off and make proteins; [and] quite a few, although we know they are there, we really do not have a good understanding of what they do. "This leads to a much more complex picture." The researchers now hope to scale up their efforts to look at the other 99% of the genome..."

[2] University of Rochester (2007, August 31). One Species' Entire Genome Discovered Inside Another's. ScienceDaily. Retrieved November 10, 2007, backup Citat: "..."This study establishes the widespread occurrence and high frequency of a process that we would have dismissed as science fiction until just a few years ago," says W. Ford Doolittle, Canada Research Chair in Comparative Microbial Genomics at Dalhousie University, who is not connected to the study. "This is stunning evidence for increased frequency of gene transfer."..."This parasite has implanted itself inside the cells of 70 percent of the world's invertebrates, coevolving with them. And now, we've found at least one species where the parasite's entire or nearly entire genome has been absorbed and integrated into the host's. The host's genes actually hold the coding information for a completely separate species."..."

[3] Mammals Carry a Graveyard of Viruses in Our DNA, And It Could Have a Crucial Purpose. ScienceAlert 2021, backup

[4] Ancient Viruses Are Buried in Your DNA. NYTimes Science 2017, backup

[Gregory-5] Gregory, T.R. and P.D.N. Hebert . (1999). "The modulation of DNA content: proximate causes and ultimate consequences". Genome Research. 9: 317-324.

[GregoryWeb-6] Gregory, T.R. (2005). Animal Genome Size Database. http://www.genomesize.com .

[Wahls-7] Wahls, W.P.; et al. (1990). "Hypervariable minisatellite DNA is a hotspot for homologous recombination in human cells". Cell. 60 (1): 95-103. PMID 2295091. {{cite journal}}: Eksplicit brug af et al. i: |author= (hjælp)

[8] 12 May, 2004, BBC News: 'Junk' throws up precious secret, backup Citat: "..."It is very lucky that entire genomes were mapped, as this work is showing." He added: "I think other bits of 'junk' DNA will turn out not to be junk. I think this is the tip of the iceberg, and that there will be many more similar findings."..."

[9] 2005-07-12, Sciencedaily: Rodent Social Behavior Encoded In Junk DNA, backup Citat: "..."It was considered junk DNA because it didn't seem to have any function," noted Hammock..."

[10] Paywalled: October 2004, Scientific american: The Hidden Genetic Program of Complex Organisms, tidligere link, backup Citat: "...But an overlooked regulatory system based on RNA may hold the keys to development and evolution..."

[11] April 24, 2007, Sciencedaily: 'Junk' DNA Now Looks Like Powerful Regulator, Scientists Find, backup Citat: "...Many of those snippets were located in gene-free chromosomal expanses once described by geneticists as "gene deserts." These sections are, in fact, so clogged with useful DNA bits – including the ones Bejerano and his colleagues describe – that they've been renamed "regulatory jungles."...transposons that duplicate themselves and hop around the genome. "We used to think they were mostly messing things up. Here is a case where they are actually useful," Bejerano said..."Now we've shown that transposons may be a major vehicle for evolutionary novelty," he said...."

[12] University of California, San Francisco (UCSF) (2013, April 15). Brain development is guided by junk DNA that isn't really junk. ScienceDaily, backup

[13] 25. oktober 2013, videnskab.dk: Vores ansigter formes af 'overflødigt' DNA, backup

[14] University of California - San Francisco. (2018, June 21). Not junk: 'Jumping gene' is critical for early embryo: Gene that makes up a fifth of the human genome is not a parasite, but key to the first stages of embryonic development. ScienceDaily, backup Citat: "...Only about 1 percent of the human genome encodes proteins, and researchers have long debated what the other 99 percent is good for...For example, fully half of our DNA is made up of "transposable elements," or "transposons," virus-like genetic material that has the special ability of duplicating and reinserting itself in different locations in the genome, which has led researchers to dub them genetic parasites...Now UCSF scientists have revealed that, far from being a freeloader or parasite, the most common transposon, called LINE1, which accounts for 20 percent or more of the human genome, is actually necessary for embryos to develop past the two-cell stage...The team tried eliminating LINE1 from fertilized eggs and found that the embryos completely lost their ability to progress past the two-cell phase..."We now think these early embryos are playing with fire but in a very calculated way," Ramalho-Santos said. "This could be a very robust mechanism for regulating development."..."

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