What is comparative genomics?
Comparative genomics is an exciting new field of biological research in which the genome sequences of different species - human, mouse and a wide variety of other organisms from yeast to chimpanzees - are compared. By comparing the finished reference sequence of the human genome with genomes of other organisms, researchers can identify regions of similarity and difference. This information can help scientists better understand the structure and function of human genes and thereby develop new strategies to combat human disease. Comparative genomics also provides a powerful tool for studying evolutionary changes among organisms, helping to identify genes that are conserved among species, as well as genes that give each organism its unique characteristics.
Alignment of DNA sequences is the core process in comparative genomics. An alignment is a mapping of the nucleotides in one sequence onto the nucleotides in the other sequence, with gaps introduced into one or the other sequence to increase the number of positions with matching nucleotides. Several powerful alignment algorithms have been developed to align two or more sequences.
What are the benefits of comparative genomics?
Analysis of the sequence by itself has yielded a vast amount of information. But there are many regions to which we are unable to assign any features. Other regions clearly represent genes but we have no idea what roles the encoded proteins perform in the cell. Some of these will perform vital functions whereas others will be the genetic equivalents of the floppy drive, once important functions that human evolution has rendered obsolete.
Comparing the sequence to a second genome can answer many of these questions. We can compare one with the other, locate conserved sequence segments and assess their significance. The more genomes we have, the more confident we can become of our assignments and the higher the "resolution" at which we can examine the subtleties.
Why is there an increased interest in genomics?
A complete genome sequence of an organism can be considered to be the ultimate genetic map, in the sense that the heritable characteristics are encoded within the DNA and that the order of all the nucleotides along each chromosome is known. However, knowledge of the DNA sequence does not tell us directly how this genetic information leads to the observable traits and behaviors (phenotypes) that we want to understand. Finding all the functional parts of genome sequences and using this information to improve the health of individuals and society are the focus of the next phase of the Human Genome Project (Collins et al. 2003). Comparative analyses of genome sequences will be a major part of this effort.
What Can we Learn from comparative genomics?
The basic observation in comparative genomics is a description of the matches between genomes. Information on sequence similarity among genomes is a major resource for finding functional regions and for predicting what those functions are. Predicting exactly what the function is of these noncoding sequences under selection is a major challenge. One promising approach is to collect good training sets of alignments within sequences of known functions, such as gene regulatory sequences, and use those alignments to develop statistical models for estimating a likelihood that any given alignment could be generated by that model. This type of approach could be applied to any functional category in which the conserved DNA sequence is critical to the function. For instance, it is still not clear whether conserved DNA sequences are critical to the function of replication origins; if they are not, then this analytical model will not successfully predict this important functional category, and other methods will need to be developed.
Websites for Comparative genomics
Comparative Genomics Center(DCODE) - A publicly available resourse for regulatory genome data mining. It provides tools for evolutionary comparisons, sequence alignments, and detection of functional sequence patterns. (http://www.dcode.org/)
The National Human Genome Research Institute (NHGRI) - led the Human Genome Project for the National Institutes of Health, which culminated in the completion of the full human genome sequence in April 2003. Now, NHGRI moves forward into the genomic era with research aimed at improving human health and fighting disease.
PlantGDB - the homepage for the NSF-funded project "Cyberinfrastructure for (Comparative) Plant Genome Research Through PlantGDB" (PI: Volker Brendel, Iowa State University; Co-PI: Carol Lushbough, University of South Dakota; Co-PI: Carolyn Lawrence, USDA-ARS and Iowa State University). (http://www.plantgdb.org/)
Ensembl - This site provides free access to all the data and software from the Ensembl project. Click on a species name to browse the data. (http://www.ensembl.org/)
The National Center for Biotechnology Information (NCBI) - NCBI provides an integrated approach to the use of gene and protein sequence information, the scientific literature (MEDLINE), molecular structures, and related resources.
UCSC Genome Browser - UCSC Provides genome browser, gene sorter, blat search function, and publications. (http://genome.ucsc.edu/)
Resources for Fungal Comparative Genomics - This website is intended to provide genome annotation data for the available fungal genomes. Additional genome annotations, homology searching, and best reciprocal orthologous genes have been generated for the available species and will be made downloadable this fall.
Fungal Genomes and Comparative Genomics(http://fungalgenomes.org/blog/)
EBI Training - Comparative Genomics - As part of a collaborative effort with the Sanger Institute, the Ensembl Group at the EBI is involved in outreach work as well as investigation into characteristics of the genome. The database is the result of an automatic pipeline for gene prediction, verified by protein sequence information.
Centre for Comparative Genomics -The WA Centre of Excellence in Comparative Genomics (CCG) represents a unique approach to research in Comparative Genomics. It draws together both biomedical and agricultural comparative genomics and bioinformatics activities and expertise in such a way as to promote shared understanding within and across fields of study.
Cambridge Resource Centre for Comparative Genomics -Through its expertise in chromosome sorting, the Centre will help provide the comparative genomics community with high quality chromosome-specific DNA from a wide range of species for specific research projects including comparative mapping, gene localisation, and evolutionary studies.
Comparative Genomics Laboratory
Laboratoire de Génomique Comparée -The Comparative Genomics Laboratory of UQAM was created in 2005 by Anne Bergeron and Cedric Chauve. The research developed in the laboratory is centered on the developement of mathematical models, algorithms and softwares for the comparative analysis of genomes, with a strong focus on the analysis of gene orders.(http://cgl.bioinfo.uqam.ca/)
PLATCOM - PLATCOM is an integrated system for the comparative analysis of multiple genomes. It is designed in a modular way, so that multiple tools and databases can be integrated freely and the whole system can grow easily. The PLATCOM system is built on internal databases, which consist of GenBank, Swiss-Prot, COG, KEGG, and Pairwise Comparison Database (PCDB).
KEGG: Kyoto Encyclopedia of Genes and Genomes- A grand challenge in the post-genomic era is a complete computer representation of the cell, the organism, and the biosphere, which will enable computational prediction of higher-level complexity of cellular processes and organism behaviors from genomic and molecular information. Towards this end we have been developing a bioinformatics resource named KEGG as part of the research projects of the Kanehisa Laboratories in the Bioinformatics Center of Kyoto University and the Human Genome Center of the University of Tokyo.
COMPARATIVE GENOMICS CENTRE - The Comparative Genomics Centre is a medical research centre founded by the School of Pharmacy and Molecular Sciences in association with the School of Medicine, at the James Cook University. The overall aim of the Centre is to use a variety of genetic models to study human disease from an evolutionary perspective. Housed in state-of-the-art custom built laboratories, the Comparative Genomics Centre offers a unique opportunity to research comparative genomics, molecular genetics, immunogenetics and immunology in a beautiful tropical environment adjacent to the Great Barrier Reef
RSBS (Research School of Bilogical Sciences) - RSBS research targets fields of biology with potential to deliver benefits for all Australians.Our discoveries will lead to significant advances in areas such as agriculture, environment, health and technology.
Comparative Genomics Tools