Editing GC-content (section)

==Genomic content==
=== Within-genome variation ===
The GC-ratio within a genome is found to be markedly variable. These variations in GC-ratio within the genomes of more complex organisms result in a mosaic-like formation with islet regions called [[Isochore (genetics)|isochores]].<ref>{{cite journal |author=Bernardi G |title=Isochores and the evolutionary genomics of vertebrates |journal=Gene |volume=241 |issue=1 |pages=3–17 |date=January 2000 |pmid=10607893 |doi=10.1016/S0378-1119(99)00485-0}}</ref> This results in the variations in staining intensity in [[chromosomes]].<ref>{{cite journal |vauthors=Furey TS, Haussler D |title=Integration of the cytogenetic map with the draft human genome sequence |journal=Hum. Mol. Genet. |volume=12 |issue=9 |pages=1037–44 |date=May 2003 |pmid=12700172 |url=http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12700172 |doi=10.1093/hmg/ddg113|doi-access=free }}</ref> GC-rich isochores typically include many protein-coding genes within them, and thus determination of GC-ratios of these specific regions contributes to [[gene mapping|mapping]] gene-rich regions of the genome.<ref>{{cite journal |vauthors=Sumner AT, de la Torre J, Stuppia L |title=The distribution of genes on chromosomes: a cytological approach |journal=J. Mol. Evol. |volume=37 |issue=2 |pages=117–22 |date=August 1993 |pmid=8411200 |doi=10.1007/BF02407346 |bibcode=1993JMolE..37..117S |s2cid=24677431 }}</ref><ref>{{cite journal |vauthors=Aïssani B, Bernardi G |title=CpG islands, genes and isochores in the genomes of vertebrates |journal=Gene |volume=106 |issue=2 |pages=185–95 |date=October 1991 |pmid=1937049 |doi=10.1016/0378-1119(91)90198-K }}</ref>

=== Coding sequences ===
Within a long region of genomic sequence, genes are often characterised by having a higher GC-content in contrast to the background GC-content for the entire genome.<ref name="pmid28261263">{{cite journal| author=Romiguier J, Roux C| title=Analytical Biases Associated with GC-Content in Molecular Evolution. | journal=Front Genet | year= 2017 | volume= 8 | issue=  | page= 16 | pmid=28261263 | doi=10.3389/fgene.2017.00016 | pmc=5309256 | doi-access=free }}</ref> There is evidence that the length of the [[coding region]] of a [[gene]] is directly proportional to higher G+C content.<ref>{{cite journal |vauthors=Pozzoli U, Menozzi G, Fumagalli M |title=Both selective and neutral processes drive GC content evolution in the human genome |journal=BMC Evol. Biol. |volume=8 |page=99 |year=2008 |issue=1 |pmid=18371205 |pmc=2292697 |doi=10.1186/1471-2148-8-99 |bibcode=2008BMCEE...8...99P |display-authors=etal |doi-access=free }}</ref> This has been pointed to the fact that the [[stop codon]] has a bias towards A and T nucleotides, and, thus, the shorter the sequence the higher the AT bias.<ref>{{cite journal |vauthors=Wuitschick JD, Karrer KM |title=Analysis of genomic G + C content, codon usage, initiator codon context and translation termination sites in ''Tetrahymena thermophila'' |journal=J. Eukaryot. Microbiol. |volume=46 |issue=3 |pages=239–47 |year=1999 |pmid=10377985 |doi=10.1111/j.1550-7408.1999.tb05120.x |s2cid=28836138 }}</ref>

Comparison of more than 1,000 [[orthologous]] genes in mammals showed marked within-genome variations of the [[codon|third-codon position]] GC content, with a range from less than 30% to more than 80%.<ref name="Romiguier2010"/>

=== Among-genome variation === 
GC content is found to be variable with different organisms, the process of which is envisaged to be contributed to by variation in [[Gene-centered view of evolution|selection]], mutational bias, and biased recombination-associated [[DNA repair]].<ref>{{cite journal |author=Birdsell JA |title=Integrating genomics, bioinformatics, and classical genetics to study the effects of recombination on genome evolution |journal=Mol. Biol. Evol. |volume=19 |issue=7 |pages=1181–97 |date=1 July 2002|pmid=12082137 |url=http://mbe.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12082137 |doi=10.1093/oxfordjournals.molbev.a004176|citeseerx=10.1.1.337.1535 }}</ref>

The average GC-content in human genomes ranges from 35% to 60% across 100-Kb fragments, with a mean of 41%.<ref name="IHSGC2001">{{cite journal |author=International Human Genome Sequencing Consortium | title = Initial sequencing and analysis of the human genome | journal = Nature | volume = 409 | issue = 6822 | pages = 860–921 | date = Feb 2001 | pmid = 11237011 | doi = 10.1038/35057062 | bibcode = 2001Natur.409..860L | doi-access = free | hdl = 2027.42/62798 | hdl-access = free }} (page 876)</ref><!--The "Romiguier2010" paper provides a mean GC level at the third codon position in genes. Since protein coding regions are massively overrepresented in GC-rich DNA, their number (46%) is much higher than the genomic mean.--> The GC-content of [[Yeast]] (''[[Saccharomyces cerevisiae]]'') is 38%,<ref>[https://www.ncbi.nlm.nih.gov/sites/entrez?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=128 Whole genome data of ''Saccharomyces cerevisiae'' on NCBI]</ref> and that of another common [[model organism]], thale cress (''[[Arabidopsis thaliana]]''), is 36%.<ref>[https://www.ncbi.nlm.nih.gov/sites/entrez?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=116 Whole genome data of '' Arabidopsis thaliana'' on NCBI]</ref> Because of the nature of the [[genetic code]], it is virtually impossible for an organism to have a genome with a GC-content approaching either 0% or 100%. However, a species with an extremely low GC-content is ''[[Plasmodium falciparum]]'' (GC% = ~20%),<ref>[https://www.ncbi.nlm.nih.gov/sites/entrez?db=genomeprj&cmd=Retrieve&dopt=Overview&list_uids=148 Whole genome data of ''Plasmodium falciparum'' on NCBI]</ref> and it is usually common to refer to such examples as being AT-rich instead of GC-poor.<ref>{{cite journal |vauthors=Musto H, Cacciò S, Rodríguez-Maseda H, Bernardi G |title=Compositional constraints in the extremely GC-poor genome of ''Plasmodium falciparum'' |journal=Mem. Inst. Oswaldo Cruz |volume=92 |issue=6 |pages=835–41 |year=1997 |pmid=9566216 |url=http://www.scielo.br/pdf/mioc/v92n6/3431.pdf |doi=10.1590/S0074-02761997000600020|doi-access=free }}</ref>

Several mammalian species (e.g., [[shrew]], [[microbat]], [[tenrec]], [[rabbit]]) have independently undergone a marked increase in the GC-content of their genes. These GC-content changes are correlated with species [[Phenotypic trait|life-history traits]] (e.g., body mass or longevity) and [[genome size]],<ref name="Romiguier2010">{{Cite journal|last1=Romiguier|first1=Jonathan|last2=Ranwez|first2=Vincent|last3=Douzery|first3=Emmanuel J. P.|last4=Galtier|first4=Nicolas|date=2010-08-01|title=Contrasting GC-content dynamics across 33 mammalian genomes: Relationship with life-history traits and chromosome sizes|journal=Genome Research|language=en|volume=20|issue=8|pages=1001–1009|doi=10.1101/gr.104372.109|issn=1088-9051|pmc=2909565|pmid=20530252}}</ref>  and might be linked to a molecular phenomenon called the GC-biased [[gene conversion]].<ref name=Duret2009>{{cite journal |vauthors=Duret L, Galtier N |s2cid=9126286 |title=Biased gene conversion and the evolution of mammalian genomic landscapes |journal=Annu Rev Genom Hum Genet |volume=10 |pages=285–311 |year=2009 |pmid=19630562 |doi=10.1146/annurev-genom-082908-150001 }}</ref>