remove one or more nucleotides from the dna

7/25/2019 Remove One or More Nucleotides From the DNA

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remove one or more nucleotides from the DNA. Like insertions, these mutations can

alter the reading frame of the gene. In general, they are irreversible: Though exactly

the same seuence might in theory be restored by an insertion, trans!osable

elements able to revert a very short deletion "say #$% bases& in any location either

are highly unlikely to exist or do not exist at all.

Large'scale mutations in chromosomal structure, including:

Am!li(cations "or gene du!lications& leading to multi!le co!ies of all chromosomal

regions, increasing the dosage of the genes located )ithin them.

Deletions of large chromosomal regions, leading to loss of the genes )ithin those

regions.

*utations )hose e+ect is to uxta!ose !reviously se!arate !ieces of DNA,

!otentially bringing together se!arate genes to form functionally distinct fusion

genes "e.g., bcr'abl&. These include:

-hromosomal translocations: interchange of genetic !arts from nonhomologous

chromosomes.

Interstitial deletions: an intra'chromosomal deletion that removes a segment of DNA

from a single chromosome, thereby a!!osing !reviously distant genes. or exam!le,

cells isolated from a human astrocytoma, a ty!e of brain tumor, )ere found to have

a chromosomal deletion removing seuences bet)een the /fused in glioblastoma/

"(g& gene and the rece!tor tyrosine kinase /ros/, !roducing a fusion !rotein "I0'

123&. The abnormal I0'123 fusion !rotein has constitutively active kinase activity

that causes oncogenic transformation "a transformation from normal cells to cancer

cells&.

-hromosomal inversions: reversing the orientation of a chromosomal segment.

Loss of hetero4ygosity: loss of one allele, either by a deletion or a recombination

event, in an organism that !reviously had t)o di+erent alleles.

gene duplicationGene duplication(or chromosomal duplicationor gene amplification) is a major mechanismthrough which new genetic material is generated duringmolecular evolution. It can be defined asany duplication of a region of DNAthat contains agene. Gene duplications can arise as products ofseveral types of errors in DNA replication and repair machinery as well as through fortuitous captureby selfish genetic elements. ommon sources of gene duplications include ectopic homologousrecombination! retrotranspositionevent!aneuploidy!polyploidy! and replication slippage."#$

Mechanisms of duplication"edit$

Ectopic Recombination"edit$

Duplications arise from an event termedune%ual crossing&overthat occurs during meiosis between

misaligned homologous chromosomes.'he chance of this happening is a function of the degree of
https://en.wikipedia.org/wiki/Molecular_evolutionhttps://en.wikipedia.org/wiki/Molecular_evolutionhttps://en.wikipedia.org/wiki/DNAhttps://en.wikipedia.org/wiki/DNAhttps://en.wikipedia.org/wiki/Genehttps://en.wikipedia.org/wiki/Genehttps://en.wikipedia.org/wiki/Homologous_recombinationhttps://en.wikipedia.org/wiki/Homologous_recombinationhttps://en.wikipedia.org/wiki/Retrotransposonhttps://en.wikipedia.org/wiki/Aneuploidyhttps://en.wikipedia.org/wiki/Aneuploidyhttps://en.wikipedia.org/wiki/Aneuploidyhttps://en.wikipedia.org/wiki/Polyploidyhttps://en.wikipedia.org/wiki/Replication_slippagehttps://en.wikipedia.org/wiki/Gene_duplication#cite_note-Zhang_2003-1https://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=1https://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=2https://en.wikipedia.org/wiki/Unequal_crossing-overhttps://en.wikipedia.org/wiki/Unequal_crossing-overhttps://en.wikipedia.org/wiki/DNAhttps://en.wikipedia.org/wiki/Genehttps://en.wikipedia.org/wiki/Homologous_recombinationhttps://en.wikipedia.org/wiki/Homologous_recombinationhttps://en.wikipedia.org/wiki/Retrotransposonhttps://en.wikipedia.org/wiki/Aneuploidyhttps://en.wikipedia.org/wiki/Polyploidyhttps://en.wikipedia.org/wiki/Replication_slippagehttps://en.wikipedia.org/wiki/Gene_duplication#cite_note-Zhang_2003-1https://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=1https://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=2https://en.wikipedia.org/wiki/Unequal_crossing-overhttps://en.wikipedia.org/wiki/Molecular_evolution


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sharing of repetitive elements between two chromosomes. 'he product of this recombination are a

duplication at the site of the echange and a reciprocal deletion. ctopic recombination is typically

mediated by se%uence similarity at the duplicate brea*points! which form direct repeats. +epetitive

genetic elements such astransposableelements offer one source of repetitive DNA that can facilitate

recombination! and they are often found at duplication brea*points in plants and mammals.",$

-chematic of a region of a chromosome before and after a duplication event

Replication Slippage"edit$

+eplication slippageis an error in DNA replication that can produce duplications of short genetic

se%uences. During replication DNA polymerasebegins to copy the DNA. At some point during the

replication process! the polymerase dissociates from the DNA and replication stalls. hen the

polymerase reattaches to the DNA strand! it aligns the replicating strand to an incorrect position and

incidentally copies the same section more than once. +eplication slippage is also often facilitated by

repetitive se%uence! but re%uires only a few bases of similarity.

Retrotransposition"edit$

During cellular invasion by a replicating retroelement or retrovirus! viral proteins copy their genome

by reverse transcribing +NA to DNA. If viral proteins aberrantly attach to cellular m+NA! they can

reverse transcribe copies of genes to create retrogenes. +etrogenes usually lac* intronic se%uence!

and often contain poly A se%uences that are also integrated into the genome. /any retrogenes

display changes in gene regulation in comparison to their parental gene se%uences! which

sometimes results in novel functions.

Aneuploidy"edit$
https://en.wikipedia.org/wiki/Transposablehttps://en.wikipedia.org/wiki/Gene_duplication#cite_note-2https://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=3https://en.wikipedia.org/wiki/Replication_slippagehttps://en.wikipedia.org/wiki/DNA_polymerasehttps://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=4https://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=5https://en.wikipedia.org/wiki/Transposablehttps://en.wikipedia.org/wiki/Gene_duplication#cite_note-2https://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=3https://en.wikipedia.org/wiki/Replication_slippagehttps://en.wikipedia.org/wiki/DNA_polymerasehttps://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=4https://en.wikipedia.org/w/index.php?title=Gene_duplication&action=edit&section=5


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Aneuploidyoccurs when nondisjunction at a single chromosome results in an abnormal number of

chromosomes. Aneuploidy is often harmful and in mammals regularly leads to spontaneous

abortions (miscarriages). -ome aneuploid individuals are viable! for eample trisomy ,# in humans

which leads toDown syndrome.Aneuploidy often alters gene dosage in ways that are detrimental to

the organism! and therefore is unli*ely to spread through populations.

Whole Genome Duplication

hole genome duplication! or polyploidyis a product ofnondisjunctionduring meiosis which results

in additional copies of the entire genome. 0olyploidy is common in plants! but historically has also

occurred in animals! with two rounds of whole genome duplication in the vertebrate lineage leading

to humans."1$After whole genome duplications many sets of additional genes are eventually lost!

returning to singleton state. 2owever! retention of many genes! most notably 2o genes! has led to

adaptive innovation.

0olyploid is also a well *nown source of speciation! as offspring! which have different numbers of

chromosomes compared to parent species! are often unable to interbreed with non&polyploid

organisms. hole genome duplications are thought to be less detrimental than aneuploidy as the

relative dosage of individual genes should be the same

Loss of heterozygosity

Loss of heterozygosity(LO!is a gross chromosomal event that results in loss of the entire geneand the surrounding chromosomal region. "#$

/ost diploid cells! for eample humansomatic cells! contain two copies of the genome! one fromeach parent (chromosome pair)3 each copy contains approimately 1 billion bases(Adenine(A)! Guanine(G)!ytosine() or 'hymine(')). 4or the majority of positions in the genomethe base present is consistent between individuals! however a small percentage may containdifferent bases (usually one of two for instance 5A6 or 5G6) and these positions are called 5singlenucleotide polymorphisms6or 5-N0s6. hen the genomic copies derived from each parent havedifferent bases for these polymorphic regions (-N0s) the region is said to be hetero7ygous. /ost ofthe chromosomes within somatic cellsof individuals are paired! allowing for -N0 locations to bepotentially hetero7ygous. 2owever! one parental copy of a region can sometimes be lost! whichresults in the region having just one copy. 'he single copy cannot be hetero7ygous at -N0 locationsand therefore the region shows loss of hetero7ygosity (892). 8oss of hetero7ygosity due to loss ofone parental copy in a region is also calledhemi7ygosityin that region.

In cancer"edit$

'he loss of hetero7ygosity is a common occurrence incancer! where it indicates the absence of a

functional tumor suppressor genein the lost region. 2owever! many people remain healthy with such

a loss! because there still is one functional gene left on the other chromosome of the chromosome

pair. 2owever! the remaining copy of the tumor suppressor gene can be inactivated by a point
https://en.wikipedia.org/wiki/Aneuploidyhttps://en.wikipedia.org/wiki/Down_syndromehttps://en.wikipedia.org/wiki/Down_syndromehttps://en.wikipedia.org/wiki/Down_syndromehttps://en.wikipedia.org/wiki/Polyploidhttps://en.wikipedia.org/wiki/Nondisjunctionhttps://en.wikipedia.org/wiki/Nondisjunctionhttps://en.wikipedia.org/wiki/Gene_duplication#cite_note-3https://en.wikipedia.org/wiki/Hox_genehttps://en.wikipedia.org/wiki/Heterozygosityhttps://en.wikipedia.org/wiki/Heterozygosityhttps://en.wikipedia.org/wiki/Loss_of_heterozygosity#cite_note-1https://en.wikipedia.org/wiki/Somatic_Cellhttps://en.wikipedia.org/wiki/Somatic_Cellhttps://en.wikipedia.org/wiki/Genomehttps://en.wikipedia.org/wiki/Chromosome_pairhttps://en.wikipedia.org/wiki/Adeninehttps://en.wikipedia.org/wiki/Guaninehttps://en.wikipedia.org/wiki/Cytosinehttps://en.wikipedia.org/wiki/Cytosinehttps://en.wikipedia.org/wiki/Cytosinehttps://en.wikipedia.org/wiki/Thyminehttps://en.wikipedia.org/wiki/Thyminehttps://en.wikipedia.org/wiki/Single_nucleotide_polymorphismhttps://en.wikipedia.org/wiki/Single_nucleotide_polymorphismhttps://en.wikipedia.org/wiki/Single_nucleotide_polymorphismhttps://en.wikipedia.org/wiki/Zygosity#Heterozygoushttps://en.wikipedia.org/wiki/Somatic_cellhttps://en.wikipedia.org/wiki/Zygosity#Hemizygoushttps://en.wikipedia.org/wiki/Zygosity#Hemizygoushttps://en.wikipedia.org/w/index.php?title=Loss_of_heterozygosity&action=edit&section=1https://en.wikipedia.org/wiki/Cancerhttps://en.wikipedia.org/wiki/Cancerhttps://en.wikipedia.org/wiki/Tumor_suppressor_genehttps://en.wikipedia.org/wiki/Chromosome_pairhttps://en.wikipedia.org/wiki/Chromosome_pairhttps://en.wikipedia.org/wiki/Point_mutationhttps://en.wikipedia.org/wiki/Aneuploidyhttps://en.wikipedia.org/wiki/Down_syndromehttps://en.wikipedia.org/wiki/Polyploidhttps://en.wikipedia.org/wiki/Nondisjunctionhttps://en.wikipedia.org/wiki/Gene_duplication#cite_note-3https://en.wikipedia.org/wiki/Hox_genehttps://en.wikipedia.org/wiki/Heterozygosityhttps://en.wikipedia.org/wiki/Loss_of_heterozygosity#cite_note-1https://en.wikipedia.org/wiki/Somatic_Cellhttps://en.wikipedia.org/wiki/Genomehttps://en.wikipedia.org/wiki/Chromosome_pairhttps://en.wikipedia.org/wiki/Adeninehttps://en.wikipedia.org/wiki/Guaninehttps://en.wikipedia.org/wiki/Cytosinehttps://en.wikipedia.org/wiki/Thyminehttps://en.wikipedia.org/wiki/Single_nucleotide_polymorphismhttps://en.wikipedia.org/wiki/Single_nucleotide_polymorphismhttps://en.wikipedia.org/wiki/Zygosity#Heterozygoushttps://en.wikipedia.org/wiki/Somatic_cellhttps://en.wikipedia.org/wiki/Zygosity#Hemizygoushttps://en.wikipedia.org/w/index.php?title=Loss_of_heterozygosity&action=edit&section=1https://en.wikipedia.org/wiki/Cancerhttps://en.wikipedia.org/wiki/Tumor_suppressor_genehttps://en.wikipedia.org/wiki/Chromosome_pairhttps://en.wikipedia.org/wiki/Chromosome_pairhttps://en.wikipedia.org/wiki/Point_mutation


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mutation!leaving no tumor suppressor gene to protect the body. 8oss of hetero7ygosity does not

imply a reversal to the homo7ygous state.

"nudson t#o$hit hypothesis of tumorigenesis"edit$

Main article:Knudson hypothesis

%irst it&'he first hit is classically thought of as a point mutation that inactivates one copy of

a tumor suppressor gene ('-G)! such as +b#. In hereditary cancer syndromes! individuals are

born with the first hit. 'he individual does not develop cancer at this point because the remaining

'-G allele on the other locus is still functioning normally.

Second it&hile the second hit is commonly assumed to be adeletionthat results in loss

of the remaining functioning '-G allele! the original published mechanism of +:# 892 was

mitotic recombination;gene conversion;copy&neutral 892! not deletion. 'here is a critical

difference between deletion and N&892! as the latter mechanism cannot be detected by

comparative genomic hybridi7ation (G2)&based gene copy number counting! and re%uires

allelic genotyping. ither way! 892 leaves only non&functioning alleles of the '-G! and the

individual goes on to develop cancer.

'opy$neutral LO"edit$

opy&neutral 892 is thus called because no net change in the copy number occurs in the affected

individual. 9ther names for copy&neutral 892 are ac%uired uniparental disomy(


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reast 'ancer and R'A)*+g$enes :+A# and :+A, show loss of hetero7ygosity insamplings of tumors from patients who have germline mutations. :+A#;, are genes that produceproteins which regulate the DNA repair pathway by binding to +adB#.

Detection

8oss of hetero7ygosity can be identified in cancers by noting the presence ofhetero7ygosityat a

genetic locusin an organisms germlineDNA! and the absence of hetero7ygosity at that locus in the

cancer cells. 'his is often done using polymorphicmar*ers! such asmicrosatellitesor single&

nucleotide polymorphisms! for which the two parents contributed differentalleles.Genome&wide

892 status of fresh or paraffin embedded tissue samples can be assessed by virtual

*aryotypingusing -N0 arrays.

In asexual organisms

It has been proposed that 892 may limit the longevity of aseual organisms. "E$"?$'he minor allele in

hetero7ygous areas of the genome is li*ely to have mild fitness conse%uences compared to de&novo

mutations because selection has had time to remove deleterious alleles. henallelic gene

conversionremoves the major allele at these sites organisms are li*ely to eperience a mild decline

in fitness. :ecause 892 is much more common than de&novo mutation! and because the fitness

conse%uences are closer to neutrality! this process should drive /ullers ratchet more %uic*ly than

de&novo mutations. hile this process has received little eperimental investigation! it is *nown that

major signature of aseuality in meta7oan genomes appears to be genome wide 892! a sort of anti&

meselson effect.
https://en.wikipedia.org/wiki/Heterozygosityhttps://en.wikipedia.org/wiki/Heterozygosityhttps://en.wikipedia.org/wiki/Heterozygosityhttps://en.wikipedia.org/wiki/Locus_(genetics)https://en.wikipedia.org/wiki/Locus_(genetics)https://en.wikipedia.org/wiki/Germlinehttps://en.wikipedia.org/wiki/DNAhttps://en.wikipedia.org/wiki/Polymorphism_(biology)https://en.wikipedia.org/wiki/Microsatellite_(genetics)https://en.wikipedia.org/wiki/Single-nucleotide_polymorphismshttps://en.wikipedia.org/wiki/Single-nucleotide_polymorphismshttps://en.wikipedia.org/wiki/Alleleshttps://en.wikipedia.org/wiki/Alleleshttps://en.wikipedia.org/wiki/Alleleshttps://en.wikipedia.org/wiki/Virtual_Karyotypehttps://en.wikipedia.org/wiki/Virtual_Karyotypehttps://en.wikipedia.org/wiki/Loss_of_heterozygosity#cite_note-7https://en.wikipedia.org/wiki/Loss_of_heterozygosity#cite_note-8https://en.wikipedia.org/wiki/Loss_of_heterozygosity#cite_note-8https://en.wikipedia.org/w/index.php?title=Allelic_gene_conversion&action=edit&redlink=1https://en.wikipedia.org/w/index.php?title=Allelic_gene_conversion&action=edit&redlink=1https://en.wikipedia.org/w/index.php?title=Allelic_gene_conversion&action=edit&redlink=1https://en.wikipedia.org/wiki/Meselson_effecthttps://en.wikipedia.org/wiki/Meselson_effecthttps://en.wikipedia.org/wiki/Heterozygosityhttps://en.wikipedia.org/wiki/Locus_(genetics)https://en.wikipedia.org/wiki/Germlinehttps://en.wikipedia.org/wiki/DNAhttps://en.wikipedia.org/wiki/Polymorphism_(biology)https://en.wikipedia.org/wiki/Microsatellite_(genetics)https://en.wikipedia.org/wiki/Single-nucleotide_polymorphismshttps://en.wikipedia.org/wiki/Single-nucleotide_polymorphismshttps://en.wikipedia.org/wiki/Alleleshttps://en.wikipedia.org/wiki/Virtual_Karyotypehttps://en.wikipedia.org/wiki/Virtual_Karyotypehttps://en.wikipedia.org/wiki/Loss_of_heterozygosity#cite_note-7https://en.wikipedia.org/wiki/Loss_of_heterozygosity#cite_note-8https://en.wikipedia.org/w/index.php?title=Allelic_gene_conversion&action=edit&redlink=1https://en.wikipedia.org/w/index.php?title=Allelic_gene_conversion&action=edit&redlink=1https://en.wikipedia.org/wiki/Meselson_effect

remove one or more nucleotides from the dna

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