Comparative genomics

Comparative genomics is a field of biological research in which the genomic features of different organisms are compared. The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural landmarks. 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. The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. 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, genome and molecular evolution are inferred and this may in turn be put in the context of, for example, phenotypic evolution or population genetics. Comparative genomics is a field of biological research in which the genomic features of different organisms are compared. The genomic features may include the DNA sequence, genes, gene order, regulatory sequences, and other genomic structural landmarks. 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. The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. 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, genome and molecular evolution are inferred and this may in turn be put in the context of, for example, phenotypic evolution or population genetics. 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. 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. 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. It has also showed the extreme diversity of the genecomposition in different evolutionary lineages. See also: History of genomics Comparative genomics has a root in the comparison of virus genomes in the early 1980s. 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. 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. The first complete genome sequence of a cellular organism, that of Haemophilus influenzae Rd, was published in 1995. The second genome sequencing paper was of the small parasitic bacterium Mycoplasma genitalium published in the same year. Starting from this paper, reports on new genomes inevitably became comparative-genomic studies. The first high-resolution whole genome comparison system was developed in 1998 by Art Delcher, Simon Kasif and Steven Salzberg and applied to the comparison of entire highly related microbial organisms with their collaborators at the Institute for Genomic Research (TIGR). The system is called MUMMER and was described in a publication in Nucleic Acids Research in 1999. The system helps researchers to identify large rearrangements, single base mutations, reversals, tandem repeat expansions and other polymorphisms. In bacteria, MUMMER enables the identification of polymorphisms that are responsible for virulence, pathogenicity, and anti-biotic resistance. The system was also applied to the Minimal Organism Project at TIGR and subsequently to many other comparative genomics projects. Saccharomyces cerevisiae, the baker's yeast, was the first eukaryote to have its complete genome sequence published in 1996. After the publication of the roundworm Caenorhabditis elegans genome in 1998 and together with the fruit fly Drosophila melanogaster genome in 2000, 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. At the same time, Bonnie Berger, Eric Lander, and their team published a paper on whole-genome comparison of human and mouse. 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. 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.