Comparative genomics

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Whole genome alignment is a typical method in comparative genomics. This alignment of eight Yersinia bacteria genomes reveals 78 locally collinear blocks conserved among all eight taxa. Each chromosome has been laid out horizontally and homologous blocks in each genome are shown as identically colored regions linked across genomes. Regions that are inverted relative to Y. pestis KIM are shifted below a genome's center axis.[1]

Comparative genomics is a field of biological research in which the genomic features of different organisms are compared.[2][3] The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural landmarks.[3] In this branch of genomics, whole or large parts of genomes resulting from genome projects are compared to study basic biological similarities and differences as well as evolutionary relationships between organisms.[2][4][5] The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionary conserved between them.[6] Therefore, comparative genomic approaches start with making some form of alignment of genome sequences and looking for orthologous sequences (sequences that share a common ancestry) in the aligned genomes and checking to what extent those sequences are conserved. Based on these, inference on genome and molecular evolution are made and this may in turn be put in the context of, for example, phenotypic evolution or population genetics.[7]

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.[2][8] With the explosion in the number of genome project 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.[9] Comparative genomics has revealed high levels of similarity between closely related oganisms, such as humans and chimpanzees, and, more surprisingly, similarity between seemingly distantly related organisms, such as humans and the yeast Saccharomyces cerevisiae.[4] It has also showed the extreme diversity of the gene composition in different evolutionary lineages.[8]

History[edit]

See also: History of genomics

Comparative genomics has a root in the comparison of virus genomes in the early 1980s.[8] For example, small RNA viruses infecting animals (picornaviruses) and those infecting plants (cowpea mosaic virus) were compared and turned out to share significant sequence similarity and, in part, the order of their genes.[10] In 1986, the first comparative genomic study at a larger scale was published, comparing the genomes of varicella-zoster virus and Epstein-Barr virus that contained more than 100 genes each.[11]

The first complete genome sequence of a cellular organism, that of Haemophilus influenzae Rd, was published in 1995.[12] The second genome sequencing paper was of the small parasitic bacterium Mycoplasma genitalium published in the same year.[13] Starting from this paper, reports on new genomes inevitably became comparative-genomic studies.[8]

Saccharomyces cerevisiae, the baker's yeast, was the first eukaryote to have its complete genome sequence published in 1996.[14] After the publication of the roundworm Caenorhabditis elegans genome in 1998[15] and together with the fruit fly Drosophila melanogaster genome in 2000,[16] Gerald M. Rubin and his team published a paper titled "Comparative Genomics of the Eukaryotes", in which they compared the genomes of the eukaryotes D. melanogaster, C. elegans, and S. cerevisiae, as well as the prokaryote H. influenzae.[17]

With the publication of the large genomes of vertebrates in the 2000s, including human, the Japanese pufferfish Takifugu rubripes, and mouse, precomputed results of large genome comparisons have been released for downloading or for visualization in a genome browser. Instead of undertaking their own analyses, most biologists can access these large cross-species comparisons and avoid the impracticality caused by the size of the genomes.[18]

Next-generation sequencing methods, which were first introduced in 2007, have produced an enormous amount of genomic data and have allowed researchers to generate multiple (prokaryotic) draft genome sequences at once. These methods can also quickly uncover single-nucleotide polymorphisms, insertions and deletions by mapping unassembled reads against a well annotated reference genome, and thus provide a list of possible gene differences that may be the basis for any functional variation among strains.[9]

Evolutionary principles[edit]

One character of Biology is evolution, evolutionary theory is also the theoretical foundation of comparative genomics, and at the same time the results of comparative genomics unprecedentedly enriched and developed the theory of evolution. When two or more of the genome sequence compared, in essence get the evolutionary relationships of the sequence in the phylogenetic tree. Increased genome information of study makes molecular evolution, gene function at the genome level possible. Based on a variety of biological genome data and the study of vertical and horizontal evolution process, can understand vital parts of gene structure and its regulation function for life. But as a result in biological genome about 1.5% ~ 14.5% of the genes related to "lateral migration phenomenon", namely the gene transfer between populations which can exist at the same time, the differences in sequence result has nothing to do with the evolution. So in the system analysis, it needs to establish a relatively complete evolution model, in order to avoid gene transfer and the influence of the lack of more appropriate species which are conserved sequence.

Similarity of related genomes is the basis of comparative genomics. Two creatures which have a recent common ancestor, the species difference genomes between them were evolved from ancestors’ genome, the closer the two organisms on the evolutionary stages, the higher their genome correlated. If there is close relationship between them, then their genome will behave like linear (synteny), namely some or all of the genetic sequences are conservative. So scientists can use the homology of the sequence and structure of encoding between mode genomes, by known genome mapping information to locate other genes in the genome, so as to reveal the potential function of the genes, clarify evolutionary relationship and the inner structure of the genome.

Orthologous sequences are separate because of speciation: a gene exists in the original species, the species divided into two species, so genes in new species are orthologous. Paralogy sequences are separate by gene cloning (gene duplication): if a particular gene in the biology is copied, then the copy of the two sequences is paralogy. A pair of orthologous sequences is called orthologous pairs (orthologs), a pair of paralogy sequence is called collateral pairs (paralogs). Orthologous pairs usually have the same or similar function, but not necessarily on collateral pairs: due to the lack of the power of natural selection, the original duplicate copy of the genes are variation and get free new functions.

Human FOXP2 gene and evolutionary conservation is shown in and multiple alignment (at bottom of figure) in this image from the UCSC Genome Browser. Note that conservation tends to cluster around coding regions (exons).

Comparative genomics exploits both similarities and differences in the proteins, RNA, and regulatory regions of different organisms to infer how selection has acted upon these elements. Those elements that are responsible for similarities between different species should be conserved through time (stabilizing selection), while those elements responsible for differences among species should be divergent (positive selection). Finally, those elements that are unimportant to the evolutionary success of the organism will be unconserved (selection is neutral).

One of the important goals of the field is the identification of the mechanisms of eukaryotic genome evolution. It is however often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. For this reason comparative genomics studies of small model organisms (for example the model Caenorhabditis elegans and closely related Caenorhabditis briggsae) are of great importance to advance our understanding of general mechanisms of evolution.[19][20]

Methods[edit]

Computational approaches to genome comparison have recently become a common research topic in computer science. A public collection of case studies and demonstrations is growing, ranging from whole genome comparisons to gene expression analysis.[21] This has increased the introduction of different ideas, including concepts from systems and control, information theory, strings analysis and data mining. It is anticipated that computational approaches will become and remain a standard topic for research and teaching, while multiple courses will begin training students to be fluent in both topics.[22]

Tools[edit]

Computational tools for analyzing sequences and complete genomes are developed quickly due to the availability of large amount of genomic data. At the same time, comparative analysis tools are progressed and improved. In the challenges about these analyses, it is very important to visualize the comparative results.[23]

Visualization of sequence conservation is a tough task of comparative sequence analysis. As we know, it is highly inefficient to examine the alignment of long genomic regions manually. Internet-based genome browsers provide many useful tools for investigating genomic sequences due to integrating all sequence-based biological information on genomic regions. When we extract large amount of relevant biological data, they can be very easy to use and less time-consuming.[23]

  • UCSC Browser: This site contains the reference sequence and working draft assemblies for a large collection of genomes.[24]
  • Ensembl: The Ensembl project produces genome databases for vertebrates and other eukaryotic species, and makes this information freely available online.[25]
  • MapView: The Map Viewer provides a wide variety of genome mapping and sequencing data.[26]
  • VISTA is a comprehensive suite of programs and databases for comparative analysis of genomic sequences. It was built to visualize the results of comparative analysis based on DNA alignments. The presentation of comparative data generated by VISTA can easily suit both small and large scale of data.[27]

An advantage of using online tools is that these websites are being developed and updated constantly. There are many new settings and content can be used online to improve efficiency.[23]

Applications[edit]

See also[edit]

References[edit]

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  2. ^ a b c Touchman, J. (2010). "Comparative Genomics". Nature Education Knowledge 3 (10): 13. Retrieved 2014-01-02. 
  3. ^ a b Xia, X. (2013). Comparative Genomics. Heidelberg: Springer. ISBN 978-3-642-37145-5. 
  4. ^ a b Russel, P.J.; Hertz, P.E.; McMillan, B. (2011). Biology: The Dynamic Science (2nd ed.). Belmont, CA: Brooks/Cole. pp. 409–410. 
  5. ^ Primrose, S.B.; Twyman, R.M. (2003). Principles of Genome Analysis and Genomics (3rd ed.). Malden, MA: Blackwell Publishing. 
  6. ^ Hardison, R.C. (2003). "Comparative genomics". PLoS Biology 1 (2): e58. doi:10.1371/journal.pbio.0000058. 
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  8. ^ a b c d Koonin, E.V.; Galperin, M.Y. (2003). Sequence - Evolution - Function: Computational approaches in comparative genomics. Dordrecht: Springer Science+Business Media. 
  9. ^ a b Hu, B.; Xie, G.; Lo, C.-C.; Starkenburg, S. R.; Chain, P. S. G. (2011). "Pathogen comparative genomics in the next-generation sequencing era: genome alignments, pangenomics and metagenomics". Briefings in Functional Genomics 10 (6): 322–333. doi:10.1093/bfgp/elr042. 
  10. ^ Argos, P.; Kamer, G.; Nicklin, M.J.; Wimmer, E. (1984). "Similarity in gene organization and homology between proteins of animal picornaviruses and a plant comovirus suggest common ancestry of these virus families". Nucleic Acids Research 12 (18): 7251–7267. doi:10.1093/nar/12.18.7251. 
  11. ^ McGeoch, D.J.; Davison, A.J. (1986). "DNA sequence of the herpes simplex virus type 1 gene encoding glycoprotein gH, and identification of homologues in the genomes of varicella-zoster virus and Epstein-Barr virus". Nucleic Acids Research 14 (10): 4281–4292. doi:10.1093/nar/14.10.4281. 
  12. ^ Fleischmann R, Adams M, White O, Clayton R, Kirkness E, Kerlavage A, Bult C, Tomb J, Dougherty B, Merrick J (1995). "Whole-genome random sequencing and assembly of Haemophilus influenzae Rd". Science 269 (5223): 496–512. doi:10.1126/science.7542800. 
  13. ^ Fraser, Claire M.; et al. (1995). "The Minimal Gene Complement of Mycoplasma genitalium". Science 270 (5235): 397–404. doi:10.1126/science.270.5235.397. 
  14. ^ A. Goffeau, B. G. Barrell, H. Bussey, R. W. Davis, B. Dujon, H. Feldmann, F. Galibert, J. D. Hoheisel, C. Jacq, M. Johnston, E. J. Louis, H. W. Mewes, Y. Murakami, P. Philippsen, H. Tettelin & S. G. Oliver (1996). "Life with 6000 genes". Science 274 (5287): 546, 563–567. doi:10.1126/science.274.5287.546. PMID 8849441. 
  15. ^ The C. elegans Sequencing Consortium (1998). "Genome sequence of the nematode C. elegans: A platform for investigating biology". Science 282 (5396): 2012–2018. doi:10.1126/science.282.5396.2012. 
  16. ^ Adams MD, Celniker SE, Holt RA, et al. (2000). "The genome sequence of Drosophila melanogaster". Science 287 (5461): 2185–95. doi:10.1126/science.287.5461.2185. 
  17. ^ Rubin, G.; Yandell, M.; Wortman, J.; Gabor Miklos, G.; Nelson, C.; Hariharan, I.; Fortini, M.; Li, P.; Apweiler, R.; Fleischmann, W.; Cherry, J. M.; Henikoff, S.; Skupski, M. P.; Misra, S.; Ashburner, M.; Birney, E.; Boguski, M. S.; Brody, T.; Brokstein, P.; Celniker, S. E.; Chervitz, S. A.; Coates, D.; Cravchik, A.; Gabrielian, A.; Galle, R. F.; Gelbart, W. M.; George, R. A.; Goldstein, L. S.; Gong, F.; Guan, P. (2000). "Comparative genomics of the eukaryotes". Science 287 (5461): 2204–2215. Bibcode:2000Sci...287.2204.. doi:10.1126/science.287.5461.2204. PMC 2754258. PMID 10731134.  edit
  18. ^ Ureta-Vidal, A.; Ettwiller, L.; Birney, E. (2003). "Comparative genomics: Genome-wide analysis in metazoan eukaryotes". Nature Reviews Genetics 4 (4): 251–262. doi:10.1038/nrg1043. PMID 12671656.  edit
  19. ^ Stein LD, et al. (2003). "The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics". PLoS Biology 1 (2): E45. doi:10.1371/journal.pbio.0000045. PMC 261899. PMID 14624247. 
  20. ^ "Newly Sequenced Worm a Boon for Worm Biologists". PLoS Biology 1 (2): e4–e4. 2003. doi:10.1371/journal.pbio.0000044.  edit
  21. ^ Cristianini N and Hahn M (2006). Introduction to Computational Genomics. Cambridge University Press. ISBN 0-521-67191-4. 
  22. ^ Via, Allegra; Javier De Las Rivas, Teresa K. Attwood, David Landsman, Michelle D. Brazas, Jack A. M. Leunissen, Anna Tramontano, Maria Victoria Schneider (2011-10-27). "Ten Simple Rules for Developing a Short Bioinformatics Training Course". PLoS Comput Biol 7 (10): e1002245. doi:10.1371/journal.pcbi.1002245. Retrieved 2011-12-03. 
  23. ^ a b c Bergman NH, ed. (2007). Comparative Genomics: Volumes 1 and 2. Totowa (NJ): Humana Press. ISBN 978-193411-537-4. PMID 21250292. 
  24. ^ "UCSC Browser". 
  25. ^ "Ensembl Genome Browser". 
  26. ^ "Map Viewer". 
  27. ^ "VISTA tools". 

Further reading[edit]

External links[edit]