Editing Candida albicans (section)

==Genome==
[[File:Candida Gram stain.jpg|thumb|right|''Candida albicans'' visualized by Gram stain and microscopy. Note the hyphae and chlamydospores, which are 2–4 μm in diameter.]]

[[File:Candida albicans PHIL 3192 lores.jpg|thumb|''Candida albicans'' growing on [[Sabouraud agar]]]]

The genome of ''C. albicans'' is almost 16Mb for the haploid size (28Mb for the diploid stage) and consists of 8 sets of chromosome pairs called chr1A, chr2A, chr3A, chr4A, chr5A, chr6A, chr7A and {{not a typo|chrRA}}. The second set (''C. albicans'' is diploid) has similar names but with a B at the end. Chr1B, chr2B, ... and chrRB. The whole genome contains 6,198 [[open reading frame]]s (ORFs). Seventy percent of these ORFs have not yet been characterized. The whole genome has been sequenced making it one of the first fungi to be completely sequenced (next to ''Saccharomyces cerevisiae'' and ''Schizosaccharomyces pombe'').<ref name="Calderone"/><ref name="candidagenome.org"/> All open reading frames (ORFs) are also available in [[Gateway Technology|Gateway-adapted vectors]]. Next to this ORFeome there is also the availability of a GRACE (gene replacement and conditional expression) library to study essential genes in the genome of ''C. albicans''.<ref name="Large-scale essential gene identifi">{{cite journal | vauthors = Roemer T, Jiang B, Davison J, Ketela T, Veillette K, Breton A, Tandia F, Linteau A, Sillaots S, Marta C, Martel N, Veronneau S, Lemieux S, Kauffman S, Becker J, Storms R, Boone C, Bussey H | display-authors = 6 | title = Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery | journal = Molecular Microbiology | volume = 50 | issue = 1 | pages = 167–181 | date = October 2003 | pmid = 14507372 | doi = 10.1046/j.1365-2958.2003.03697.x | s2cid = 6773779 | doi-access =  }}</ref><ref name="ReferenceB">{{cite web|url=http://www.candidagenome.org/CommunityNews.shtml|title=Candida Community News|website=www.candidagenome.org|access-date=27 March 2018|archive-date=27 October 2018|archive-url=https://web.archive.org/web/20181027230229/http://www.candidagenome.org/CommunityNews.shtml|url-status=live}}</ref> The most commonly used strains to study ''C. albicans'' are the WO-1 and SC5314 strains. The WO-1 strain is known to switch between white-opaque form with higher frequency while the SC5314 strain is the strain used for gene sequence reference.<ref>{{cite web|url=http://www.candidagenome.org/Strains.shtml#P37005|title=Candida Strains|website=www.candidagenome.org|access-date=27 March 2018|archive-date=27 October 2018|archive-url=https://web.archive.org/web/20181027232139/http://www.candidagenome.org/Strains.shtml#P37005|url-status=live}}</ref>

One of the most important features of the ''C. albicans'' genome is the high heterozygosity. At the base of this heterozygosity lies the occurrence of numeric and structural [[chromosome|chromosomal]] rearrangements and changes as means of generating genetic diversity by chromosome length polymorphisms (contraction/expansion of repeats), reciprocal [[chromosomal translocation|translocations]], chromosome [[Deletion (genetics)|deletions]], Nonsynonymous [[single-nucleotide polymorphism]]s and [[trisomy]] of individual chromosomes. These [[karyotype|karyotypic]] alterations lead to changes in the phenotype, which is an [[adaptation]] strategy of this fungus. These mechanisms are further being explored with the availability of the complete analysis of the ''C. albicans'' genome.<ref>{{cite journal | vauthors = Rustchenko-Bulgac EP | title = Variations of Candida albicans electrophoretic karyotypes | journal = Journal of Bacteriology | volume = 173 | issue = 20 | pages = 6586–6596 | date = October 1991 | pmid = 1917880 | pmc = 208996 | doi = 10.1128/jb.173.20.6586-6596.1991 }}</ref><ref>{{cite journal | vauthors = Holmes AR, Tsao S, Ong SW, Lamping E, Niimi K, Monk BC, Niimi M, Kaneko A, Holland BR, Schmid J, Cannon RD | display-authors = 6 | title = Heterozygosity and functional allelic variation in the Candida albicans efflux pump genes CDR1 and CDR2 | journal = Molecular Microbiology | volume = 62 | issue = 1 | pages = 170–186 | date = October 2006 | pmid = 16942600 | doi = 10.1111/j.1365-2958.2006.05357.x | doi-access =  | s2cid = 11838673 }}</ref><ref>{{cite journal | vauthors = Jones T, Federspiel NA, Chibana H, Dungan J, Kalman S, Magee BB, Newport G, Thorstenson YR, Agabian N, Magee PT, Davis RW, Scherer S | display-authors = 6 | title = The diploid genome sequence of Candida albicans | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 19 | pages = 7329–7334 | date = May 2004 | pmid = 15123810 | pmc = 409918 | doi = 10.1073/pnas.0401648101 | doi-access = free | bibcode = 2004PNAS..101.7329J }}</ref>

An unusual feature of the genus ''Candida'' is that in many of its species (including ''C. albicans'' and ''C. tropicalis'', but not, for instance, ''C. glabrata'') the CUG [[Genetic code|codon]], which normally specifies leucine, specifies serine in these species. This is an unusual example of a departure from the standard [[genetic code]], and most such departures are in [[start codon]]s or, for [[eukaryote]]s, [[genetic code#Variations|mitochondrial genetic codes]].<ref>{{cite journal | vauthors = Ohama T, Suzuki T, Mori M, Osawa S, Ueda T, Watanabe K, Nakase T | title = Non-universal decoding of the leucine codon CUG in several Candida species | journal = Nucleic Acids Research | volume = 21 | issue = 17 | pages = 4039–4045 | date = August 1993 | pmid = 8371978 | pmc = 309997 | doi = 10.1093/nar/21.17.4039 }}</ref><ref>{{cite web |url=http://www.candidagenome.org/help/code_tables.shtml |title=CGD Help: Non-standard Genetic Codes |author1=Arnaud, MB |author2=Costanzo, MC |author3=Inglis, DO |author4=Skrzypek, MS |author5=Binkley, J |author6=Shah, P |author7=Binkley, G |author8=Miyasato, SR |author9=Sherlock, G |work=Candida Genome Database |access-date=30 October 2011 |archive-date=1 November 2018 |archive-url=https://web.archive.org/web/20181101015358/http://www.candidagenome.org/help/code_tables.shtml |url-status=live }}</ref><ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi#SG12 |title=The Alternative Yeast Nuclear Code |author=Andrzej (Anjay) Elzanowski and Jim Ostell |publisher=National Center for Biotechnology Information (NCBI) |location=Bethesda, Maryland, U.S.A. |date=7 July 2010 |access-date=30 October 2011 |work=The Genetic Codes |archive-date=13 May 2011 |archive-url=https://web.archive.org/web/20110513014234/http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi#SG12 |url-status=live }}</ref> This alteration may, in some environments, help these ''Candida'' species by inducing a permanent stress response, a more generalized form of the [[heat shock response]].<ref>{{cite journal | vauthors = Santos MA, Cheesman C, Costa V, Moradas-Ferreira P, Tuite MF | title = Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp | journal = Molecular Microbiology | volume = 31 | issue = 3 | pages = 937–947 | date = February 1999 | pmid = 10048036 | doi = 10.1046/j.1365-2958.1999.01233.x | s2cid = 28572737 | doi-access = free }}</ref> However, this different codon usage makes it more difficult to study ''C. albicans'' protein-protein interactions in the model organism ''S. cerevisiae''. To overcome this problem a ''C. albicans'' specific two-hybrid system was developed.<ref name="stynen">{{cite journal | vauthors = Stynen B, Van Dijck P, Tournu H | title = A CUG codon adapted two-hybrid system for the pathogenic fungus Candida albicans | journal = Nucleic Acids Research | volume = 38 | issue = 19 | pages = e184 | date = October 2010 | pmid = 20719741 | pmc = 2965261 | doi = 10.1093/nar/gkq725 }}</ref>

The genome of ''C. albicans'' is highly dynamic, contributed by the different CUG translation, and this variability has been used advantageously for molecular epidemiological studies and population studies in this species. The genome sequence has allowed for identifying the presence of a [[parasexual cycle]] (no detected [[meiosis|meiotic division]]) in ''C. albicans''.<ref name=Butler>{{cite journal | vauthors = Butler G, Rasmussen MD, Lin MF, Santos MA, Sakthikumar S, Munro CA, Rheinbay E, Grabherr M, Forche A, Reedy JL, Agrafioti I, Arnaud MB, Bates S, Brown AJ, Brunke S, Costanzo MC, Fitzpatrick DA, de Groot PW, Harris D, Hoyer LL, Hube B, Klis FM, Kodira C, Lennard N, Logue ME, Martin R, Neiman AM, Nikolaou E, Quail MA, Quinn J, Santos MC, Schmitzberger FF, Sherlock G, Shah P, Silverstein KA, Skrzypek MS, Soll D, Staggs R, Stansfield I, Stumpf MP, Sudbery PE, Srikantha T, Zeng Q, Berman J, Berriman M, Heitman J, Gow NA, Lorenz MC, Birren BW, Kellis M, Cuomo CA | display-authors = 6 | title = Evolution of pathogenicity and sexual reproduction in eight Candida genomes | journal = Nature | volume = 459 | issue = 7247 | pages = 657–662 | date = June 2009 | pmid = 19465905 | pmc = 2834264 | doi = 10.1038/nature08064 | bibcode = 2009Natur.459..657B }}</ref> This study of the evolution of sexual reproduction in six ''Candida'' species found recent losses in components of the major meiotic crossover-formation pathway, but retention of a minor pathway.<ref name=Butler/> The authors suggested that if ''Candida'' species undergo meiosis it is with reduced machinery, or different machinery, and indicated that unrecognized meiotic cycles may exist in many species. In another evolutionary study, introduction of partial CUG identity redefinition (from ''Candida'' species) into ''Saccharomyces cerevisiae'' clones caused a stress response that negatively affected sexual reproduction. This CUG identity redefinition, occurring in ancestors of ''Candida'' species, was thought to lock these species into a diploid or polyploid state with possible blockage of sexual reproduction.<ref>{{cite journal | vauthors = Silva RM, Paredes JA, Moura GR, Manadas B, Lima-Costa T, Rocha R, Miranda I, Gomes AC, Koerkamp MJ, Perrot M, Holstege FC, Boucherie H, Santos MA | display-authors = 6 | title = Critical roles for a genetic code alteration in the evolution of the genus Candida | journal = The EMBO Journal | volume = 26 | issue = 21 | pages = 4555–4565 | date = October 2007 | pmid = 17932489 | pmc = 2063480 | doi = 10.1038/sj.emboj.7601876 }}</ref>