Editing Comparative genomics (section)

{{Short description|Field of biological research}}
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[[File:A genome alignment of eight Yersinia isolates.png|thumb |upright=1.7|Whole genome [[Sequence alignment|alignment]] is a typical method in comparative genomics. This alignment of eight ''[[Yersinia]]'' bacteria genomes reveals 78 locally collinear blocks [[Conserved sequence|conserved]] among all eight [[taxa]]. Each chromosome has been laid out horizontally and [[Homology (biology)|homologous]] blocks in each genome are shown as identically colored regions linked across genomes. Regions that are [[Structural variation#Inversion|inverted]] relative to ''[[Yersinia pestis|Y. pestis]]'' KIM are shifted below a genome's center axis.<ref>{{cite journal |vauthors=Darling AE, Miklós I, Ragan MA |title=Dynamics of genome rearrangement in bacterial populations |journal=PLOS Genetics |volume=4 |issue=7 |pages=e1000128 |date=July 2008 |pmid=18650965 |pmc=2483231 |doi=10.1371/journal.pgen.1000128 |doi-access=free}}</ref>]]

'''Comparative genomics''' is a branch of biological research that examines [[genome]] sequences across a spectrum of [[species]], spanning from humans and mice to a diverse array of organisms from [[bacteria]] to [[chimpanzees]].<ref name=scitable>{{Cite journal| volume=3| issue=10| page=13| vauthors=Touchman J| year=2010| title=Comparative Genomics| journal=Nature Education Knowledge| url=http://www.nature.com/scitable/knowledge/library/comparative-genomics-13239404}}</ref><ref name=Xia>{{cite book |vauthors=Xia X |title=Comparative Genomics |publisher=Springer |place=Heidelberg |year=2013 |isbn=978-3-642-37145-5 |doi=10.1007/978-3-642-37146-2 |series=SpringerBriefs in Genetics |s2cid=5491782}}</ref> This large-scale holistic approach compares two or more genomes to discover the similarities and differences between the genomes and to study the [[biology]] of the individual genomes.<ref name ="Wei2004">{{cite journal | vauthors = Wei L, Liu Y, Dubchak I, Shon J, Park J | title = Comparative genomics approaches to study organism similarities and differences | journal = Journal of Biomedical Informatics | volume = 35 | issue = 2 | pages = 142–150 | date = April 2002 | pmid = 12474427 | doi = 10.1016/s1532-0464(02)00506-3 | doi-access = free }}</ref> Comparison of [[Whole genome sequencing|whole genome sequences]] provides a highly detailed view of how organisms are related to each other at the [[gene]] level. By comparing whole genome sequences, researchers gain insights into [[Genetics|genetic]] relationships between organisms and study [[Evolutionary biology|evolutionary changes]].<ref name="scitable"/> The major principle of comparative genomics is that common features of two organisms will often be encoded within the [[DNA]] that is evolutionarily [[Conserved sequence|conserved]] between them. Therefore, Comparative genomics provides a powerful tool for studying evolutionary changes among organisms, helping to identify genes that are conserved or common among species, as well as genes that give unique characteristics of each organism. Moreover, these studies can be performed at different levels of the genomes to obtain multiple perspectives about the organisms.<ref name="Wei2004"/>

The comparative genomic analysis begins with a simple comparison of the general features of genomes such as genome size, number of genes, and chromosome number. Table 1 presents data on several fully sequenced model organisms, and highlights some striking findings. For instance, while the tiny flowering plant ''Arabidopsis thaliana'' has a smaller genome than that of the fruit fly ''Drosophila melanogaster'' (157 million base pairs v. 165 million base pairs, respectively) it possesses nearly twice as many genes (25,000 v. 13,000). In fact, ''A. thaliana'' has approximately the same number of genes as humans (25,000). Thus, a very early lesson learned in the '''genomic era''' is that genome size does not correlate with evolutionary status, nor is the number of genes proportionate to genome size.<ref>{{cite journal | vauthors = Bennett MD, Leitch IJ, Price HJ, Johnston JS | title = Comparisons with Caenorhabditis (approximately 100 Mb) and Drosophila (approximately 175 Mb) using flow cytometry show genome size in Arabidopsis to be approximately 157 Mb and thus approximately 25% larger than the Arabidopsis genome initiative estimate of approximately 125 Mb | journal = Annals of Botany | volume = 91 | issue = 5 | pages = 547–557 | date = April 2003 | pmid = 12646499 | pmc = 4242247 | doi = 10.1093/aob/mcg057 }}</ref>
{| class="wikitable sortable"
|+ Table 1: Comparative genome sizes of humans and other model organisms<ref name=scitable/>
|-
! Organism !! Estimated size (base pairs) !! Chromosome number !! Estimated gene number
|-
| Human ''[[Human|(Homo sapiens)]]''
 || 3.1 billion || 46 || 25,000
|-
| Mouse ''[[House mouse|(Mus musculus)]]''
 || 2.9 billion || 40 || 25,000
|-
| Bovine ''[[Cattle|(Bos taurus)]]'' || 2.86 billion<ref>{{Cite journal |last1=Zimin |first1=Aleksey V |last2=Delcher |first2=Arthur L |last3=Florea |first3=Liliana |last4=Kelley |first4=David R |last5=Schatz |first5=Michael C |last6=Puiu |first6=Daniela |last7=Hanrahan |first7=Finnian |last8=Pertea |first8=Geo |last9=Van Tassell |first9=Curtis P |last10=Sonstegard |first10=Tad S |last11=Marçais |first11=Guillaume |last12=Roberts |first12=Michael |last13=Subramanian |first13=Poorani |last14=Yorke |first14=James A |last15=Salzberg |first15=Steven L |date=2009 |title=A whole-genome assembly of the domestic cow, Bos taurus |journal=Genome Biology |volume=10 |issue=4 |pages=R42 |doi=10.1186/gb-2009-10-4-r42 |issn=1465-6906 |pmc=2688933 |pmid=19393038 |doi-access=free}}</ref>|| 60<ref>{{Cite journal |last1=Holečková |first1=Beáta |last2=Schwarzbacherová |first2=Viera |last3=Galdíková |first3=Martina |last4=Koleničová |first4=Simona |last5=Halušková |first5=Jana |last6=Staničová |first6=Jana |last7=Verebová |first7=Valéria |last8=Jutková |first8=Annamária |date=2021-08-27 |title=Chromosomal Aberrations in Cattle |journal=Genes |volume=12 |issue=9 |pages=1330 |doi=10.3390/genes12091330 |issn=2073-4425 |pmc=8468509 |pmid=34573313 |doi-access=free}}</ref>|| 22,000<ref>{{Cite journal |last1=Elsik |first1=Christine G. |last2=Tellam |first2=Ross L. |last3=Worley |first3=Kim C. |date=2009-04-24 |title=The Genome Sequence of Taurine Cattle: A window to ruminant biology and evolution |journal=Science |volume=324 |issue=5926 |pages=522–528 |doi=10.1126/science.1169588 |issn=0036-8075 |pmc=2943200 |pmid=19390049|bibcode=2009Sci...324..522A }}</ref>
|-
| Fruit fly ''[[Drosophila melanogaster|(Drosophila melanogater)]]'' || 165 million || 8 || 13,000
|-
| Plant ''([[Arabidopsis thaliana]])'' || 157 million || 10 || 25,000
|-
| Roundworm ''([[Caenorhabditis elegans]])'' || 97 million || 12 || 19,000
|-
| Yeast ''([[Saccharomyces cerevisiae]])'' || 12 million || 32 || 6,000
|-
| Bacteria ''([[Escherichia coli]])'' || 4.6 million || 1 || 3,200
|}

In comparative genomics, [[synteny]] is the preserved order of genes on [[chromosomes]] of related species indicating their descent from a [[common ancestor]]. Synteny provides a framework in which the conservation of [[Sequence homology|homologous genes]] and [[gene order]] is identified between genomes of different species.<ref>{{cite journal | vauthors = Liu D, Hunt M, Tsai IJ | title = Inferring synteny between genome assemblies: a systematic evaluation | journal = BMC Bioinformatics | volume = 19 | issue = 1 | pages = 26 | date = January 2018 | pmid = 29382321 | pmc = 5791376 | doi = 10.1186/s12859-018-2026-4 | doi-access = free }}</ref> Synteny blocks are more formally defined as regions of chromosomes between genomes that share a common order of homologous genes derived from a common ancestor.<ref>{{cite journal | vauthors = Vergara IA, Chen N | title = Large synteny blocks revealed between Caenorhabditis elegans and Caenorhabditis briggsae genomes using OrthoCluster | journal = BMC Genomics | volume = 11 | pages = 516 | date = September 2010 | pmid = 20868500 | pmc = 2997010 | doi = 10.1186/1471-2164-11-516 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tang H, Lyons E, Pedersen B, Schnable JC, Paterson AH, Freeling M | title = Screening synteny blocks in pairwise genome comparisons through integer programming | journal = BMC Bioinformatics | volume = 12 | pages = 102 | date = April 2011 | pmid = 21501495 | pmc = 3088904 | doi = 10.1186/1471-2105-12-102 | doi-access = free }}</ref> Alternative names such as conserved synteny or [[collinearity]] have been used interchangeably.<ref>{{cite journal | vauthors = Ehrlich J, Sankoff D, Nadeau JH | title = Synteny conservation and chromosome rearrangements during mammalian evolution | journal = Genetics | volume = 147 | issue = 1 | pages = 289–296 | date = September 1997 | doi = 10.1093/genetics/147.1.289 | pmid = 9286688 | pmc = 1208112 }}</ref> Comparisons of genome synteny between and within species have provided an opportunity to study evolutionary processes that lead to the diversity of chromosome number and structure in many lineages across the tree of life;<ref>{{cite journal | vauthors = Zhang G, Li B, Li C, Gilbert MT, Jarvis ED, Wang J | title = Comparative genomic data of the Avian Phylogenomics Project | journal = GigaScience | volume = 3 | issue = 1 | pages = 26 | date = 2014-12-11 | pmid = 25671091 | pmc = 4322804 | doi = 10.1186/2047-217X-3-26 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Howe KL, Bolt BJ, Cain S, Chan J, Chen WJ, Davis P, Done J, Down T, Gao S, Grove C, Harris TW, Kishore R, Lee R, Lomax J, Li Y, Muller HM, Nakamura C, Nuin P, Paulini M, Raciti D, Schindelman G, Stanley E, Tuli MA, Van Auken K, Wang D, Wang X, Williams G, Wright A, Yook K, Berriman M, Kersey P, Schedl T, Stein L, Sternberg PW | title = WormBase 2016: expanding to enable helminth genomic research | journal = Nucleic Acids Research | volume = 44 | issue = D1 | pages = D774–D780 | date = January 2016 | pmid = 26578572 | pmc = 4702863 | doi = 10.1093/nar/gkv1217 }}</ref> early discoveries using such approaches include chromosomal conserved regions in [[nematodes]] and [[yeast]],<ref name=science.282.5396.2012>{{cite journal | title = Genome sequence of the nematode C. elegans: a platform for investigating biology | journal = Science | volume = 282 | issue = 5396 | pages = 2012–2018 | date = December 1998 | pmid = 9851916 | doi = 10.1126/science.282.5396.2012 | vauthors=((The C. elegans Sequencing Consortium)) }}</ref><ref>{{cite journal | vauthors = Wong S, Wolfe KH | title = Birth of a metabolic gene cluster in yeast by adaptive gene relocation | journal = Nature Genetics | volume = 37 | issue = 7 | pages = 777–782 | date = July 2005 | pmid = 15951822 | doi = 10.1038/ng1584 }}</ref> evolutionary history and phenotypic traits of extremely conserved [[Hox gene]] clusters across animals and [[MADS-box]] gene family in plants,<ref>{{cite journal | vauthors = Luebeck EG | title = Cancer: Genomic evolution of metastasis | journal = Nature | volume = 467 | issue = 7319 | pages = 1053–1055 | date = October 2010 | pmid = 20981088 | doi = 10.1038/4671053a | bibcode = 2010Natur.467.1053L }}</ref><ref>{{cite journal | vauthors = Ruelens P, de Maagd RA, Proost S, Theißen G, Geuten K, Kaufmann K | title = FLOWERING LOCUS C in monocots and the tandem origin of angiosperm-specific MADS-box genes | journal = Nature Communications | volume = 4 | pages = 2280 | date = 2013 | pmid = 23955420 | doi = 10.1038/ncomms3280 | bibcode = 2013NatCo...4.2280R }}</ref> and [[karyotype]] evolution in mammals and plants.<ref>{{cite journal | vauthors = Kemkemer C, Kohn M, Cooper DN, Froenicke L, Högel J, Hameister H, Kehrer-Sawatzki H | title = Gene synteny comparisons between different vertebrates provide new insights into breakage and fusion events during mammalian karyotype evolution | journal = BMC Evolutionary Biology | volume = 9 | pages = 84 | date = April 2009 | issue = 1 | pmid = 19393055 | pmc = 2681463 | doi = 10.1186/1471-2148-9-84 | doi-access = free | bibcode = 2009BMCEE...9...84K }}</ref>

Furthermore, comparing two genomes not only reveals conserved domains or synteny but also aids in detecting [[copy number variations]], [[Single-nucleotide polymorphism|single nucleotide polymorphisms (SNPs)]], [[indels]], and other [[Structural variation|genomic structural variations]].

Virtually started as soon as the whole genomes of two organisms became available (that is, the genomes of the bacteria ''[[Haemophilus influenzae]]'' and ''[[Mycoplasma genitalium]]'') in 1995, comparative genomics is now a standard component of the analysis of every new genome sequence.<ref name=scitable/><ref name=koonin>{{cite book | vauthors = Koonin EV, Galperin MY | title = Sequence - Evolution - Function: Computational approaches in comparative genomics | year = 2003 | publisher = Springer Science+Business Media | place = Dordrecht}}</ref> With the explosion in the number of [[genome projects]] due to the advancements in [[DNA sequencing]] technologies, particularly the [[next-generation sequencing]] methods in late 2000s, this field has become more sophisticated, making it possible to deal with many genomes in a single study.<ref name=hu>{{cite journal | vauthors = Hu B, Xie G, Lo CC, Starkenburg SR, Chain PS | title = Pathogen comparative genomics in the next-generation sequencing era: genome alignments, pangenomics and metagenomics | journal = Briefings in Functional Genomics | volume = 10 | issue = 6 | pages = 322–333 | date = November 2011 | pmid = 22199376 | doi = 10.1093/bfgp/elr042 | doi-access = }}</ref> Comparative genomics has revealed high levels of similarity between closely related organisms, such as humans and chimpanzees, and, more surprisingly, similarity between seemingly distantly related organisms, such as humans and the yeast ''[[Saccharomyces cerevisiae]]''.<ref name=Russell>{{cite book | vauthors = Russel PJ, Hertz PE, McMillan B | title = Biology: The Dynamic Science | edition = 2nd | year = 2011 | publisher = Brooks/Cole | place = Belmont, CA | pages = 409–410}}</ref> It has also showed the extreme diversity of the gene composition in different evolutionary lineages.<ref name=koonin/>