What is comparative genomics
- 1. COMPARATIVE GENOMICS IN CEREALS
- 2. WHAT IS COMPARATIVE GENOMICS? Analyzing & comparing genetic material from different species to study evolution, gene function, and inherited disease Understand the uniqueness between different species
- 3. Comparison of whole genome sequences provides a highly detailed view of how organisms are related to each other at the genetic level. How are genomes compared and what can these findings tell us about how the overall structure of genes and genomes have evolved?
- 4. WHY WE MAKE COMPARISON Comparative genomics is a field of biological research in which the genome sequences of different species — human, mouse, and a wide variety of other organisms from bacteria to chimpanzees — are compared. By comparing the sequences of genomes of different organisms, researchers can understand what, at the molecular level, distinguishes different life forms from each other. Comparative genomics also 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 each organism its unique characteristics.
- 5. HOW ARE GENOMES COMPARED? A simple comparison of the general features of genomes such as genome size, number of genes, and chromosome number presents an entry point into comparative genomic analysis
- 6. WHAT IS COMPARED? Gene location Gene structure Exon number Exon lengths Intron lengths Sequence similarity Gene characteristics Splice sites Codon usage Conserved synteny
- 7. Whole-genome shotgun sequencing: 1. Genome is cut into small sections 2. Each section is hundreds or a few thousand bp of DNA 3. Each section is sequenced and put in a database 4. A computer aligns all sequences together (millions of them from each chromosome) to form contigs 5. Contigs are arranged (using markers, etc) to form scaffolds
- 9. CEREAL CROP FAO's definition of cereals describes these plants as annual plants which generally belong to the gramineous family, producing grains that are used for food, feed, seed and production of industrial products. Cereal Crops: Rice Wheat, Corn or maize Barley Millet Sorghum Oat Rye
- 10. Cereals such as wheat, barley, maize, sorghum, millet and rice belong to the grass family and comprise some of the most important crops for human and animal nutrition . Comparative genomic studies in cereals have been pioneering the field of plant comparative genomics in the past decade. The first comparative studies were performed at the genetic map level. They have revealed a very good conservation of the order (colinearity) of molecular markers and of QTL for agronomic traits along the chromosomes thereby establishing evolutionary relationships between the cereal genomes.
- 11. For this reason and because of its small size, rice was promoted as a model and was chosen to be the first cereal genome sequenced. Further, the development of large EST collections and the first inter- and intra-specific comparative studies of BAC sequences from maize, sorghum, rice, wheat and barley have increased the resolution of comparative analyses and have shown that a number of rearrangements disrupting microcolinearity have occurred during the evolution of the cereal genomes in the past 50–70 million years.
- 12. Comparative genomics in the grass family (Poaceae) is of particular importance. The family comprises a number of economically important plants, such as rice (Oryza sativa L.), maize (Zea mays L.), wheat (Triticum aestivum L.), sorghum (Sorghum vulgare L.), barley (Hordeum vulgare L.), rye (Secale cereale L.), and others. Even though Poaceae species diverged over 65 million years ago, comparative mapping studies have indicated that there is a high level of gene order conservation at the macro level
- 13. development of molecular markers, and for identifying the region in the model species that might contain candidate genes responsible for a trait of interest. Rice (2n = 24), having a small genome and great economic significance, was the first grass species selected for genome sequencing
- 14. In contrast, wheat, a polyploid (2n = 6x, AA, BB, DD genomes), with a genome size 40 times larger than that of rice (Argumuganathan and Earle 1991), 25%–30% gene duplication (Anderson et al. 1992; Dubcovsky et al. 1996; Akhunov et al. 2003), and over 80% repeated DNA can clearly benefit from comparative genomics. Hexaploid wheat has a haploid chromosome complement composed of three related genomes, (A, B, and D), each containing seven chromosomes.
- 15. MICRO-COLINEARITY Micro-colinearity has been shown to be conserved in some regions between barley (Dunford et al. 1995) or wheat (Yan et al. 2003) and rice. Investigations of the Sh2/A1 orthologous region in rice, sorghum, and maize (Bennetzen and Ramakrishna 2002), and species in the Triticeae (Li and Gill 2002) showed that the region was largely colinear
- 16. WHOLE GENOME COMPARATIVE MAPPING BY SEQUENCE MATCHING Southern hybridization using anchor probes (Van Deynze et al. 1998) has been the method of choice for evaluating relationships among species and genera and can detect genome fragments estimated to be at least 80% similar. Other methods such as PCR-based fragment amplification may be an all or none reaction (dominant), may amplify nonorthologous loci, or because of primer specificity, inadequately sample sequence variation.
- 17. A U.S. National Science Foundation-funded wheat expressed sequence tag (EST) project has been studying the structure and function of the expressed portion of the wheat genome by mapping wheat unigenes to individual chromosome regions. Representative ESTs, each belonging to one of the unigenes (http://wheat.pw.usda.gov/NSF/progress_mapping.html) were used for mapping in the wheat genome utilizing 101 wheat deletion stocks, each of which contain a deletion of a defined part of a chromosome (Endo and Gill 1996), referred to as deletion mapping. As of November 2002, over 100,000 ESTs from various tissues of wheat at different stages of development have been sequenced, and 4485 wheat unigenes have been deletion mapped by this project.
- 18. MODEL PLANTS: RICE Because Arabidopsis is only distantly related to the cereals, the next plant species to be sequenced was rice. The data emerging are extensive, and some of the most interesting discoveries include: Although 81% of predicted Arabidopsis genes have a rice ortholog, only 49% of predicted rice genes have an Arabidopsis ortholog. Although gene order is hardly conserved between Arabidopsis and rice, many gene functions are conserved (light receptors, flowering pathways, stress responses, developmental pathways, etc.) There are nearly 50,000 genes in the rice genome, more than in the human genome.
- 19. CEREAL GENOME SIZES Sorghum 1000 Mb Maize 3000 Mb Barley 5000 Mb Wheat 16,000 Mb Rice 420 Mb
- 20. GENES FROM OTHER CEREAL GENOMES HAVE HOMOLOGS IN RICE
- 21. Rice–wheat genome relationships. Sorrells M E et al. Genome Res. 2003;13:1818-1827 Cold Spring Harbor Laboratory Press Rice–wheat genome relationships. Rice genome view showing the wheat chromosome arm location for the most similar wheat gene sequences. Each colored box represents a rice–wheat gene sequence match at ≥ 80% identity. When the wheat EST mapped to more than one wheat chromosome, the other color-coded locations are positioned adjacent to the first. Homologous wheat chromosome locations are grouped together.
- 22. The consensus comparative map of seven grass species shows how the genomes can be aligned in terms of "rice linkage blocks" (Gale & Devos, 1998). A radial line starting at rice, the smallest genome and innermost circle, passes through regions of similar gene content in the other species. Therefore a gene in one grass species has a predicted location in a number of other grass species. This observation has driven much sharing among researchers working on the various grass species (Phillips & Freeling, 1998).
- 23. The consensus map demonstrated several fundamental points regarding plant genomes: The conservation of gene order in the grasses is good enough to make predictions of the locations of genes in these crop species, although the level of resolution depends on the closeness of the relationship between the species being compared. The rice genome is more like the ancestral grass genome than those of the other cereals. Major chromosomal rearrangements have taken place during the evolution of the other grasses
- 24. limitations Although the level of synteny in the grasses has facilitated research in these crops, there are limits to the extent of synteny between more distantly related species. Little conservation of gene order exists between Arabidopsis and maize, even though approximately 90% of maize proteins have a homolog in Arabidopsis (Brendel et al. 2002). Therefore sequencing more plant genomes will be not only helpful but necessary.
- 25. Cultivated wheat is either tetraploid (twice the wild type chromosome number) or hexaploid (triple the wild type chromosome number). Many other crop species are polyploid, including cotton (4x), oat (6x), canola (4x), potato (4x), banana (3x), sugar cane (16x) etc
- 26. The future of comparative genomics Miller et al. (2004) have provided a comprehensive overview of what has been learned from comparative genomics, and what the future holds. Their "wish list" for future advances includes: Alignment software which can automatically and accurately handle a wide spectrum of sequences. - Better tools to identify well-conserved regions within long alignments. Precise and comprehensive formulations of the genome comparison problem (e.g. whole genome alignment). - Improved methods to evaluate genome- alignment software. - Improved tools for linking alignments to other sequence-based information.
- 27. IMPACT OF COMPARATIVE GENOMICS The impact of comparative genomics will be far- reaching. For example: "The genomic revolution is having a tremendous impact on the study of natural variation. It is making it possible finally to discover the molecular basis of complex traits, a fundamental question in evolutionary biology, and a question of immense practical importance in many other fields." (Borevitz & Nordborg, 2003) This will not only help us understand biology better, but aid in our exploitation of natural diversity for crop improvement, plant breeding efforts and biodiversity conservation. These are all important to the quality of life on earth.
Editor's Notes
- #22: Rice–wheat genome relationships. Rice genome view showing the wheat chromosome arm location for the most similar wheat gene sequences. Each colored box represents a rice–wheat gene sequence match at ≥ 80% identity. When the wheat EST mapped to more than one wheat chromosome, the other color-coded locations are positioned adjacent to the first. Homologous wheat chromosome locations are grouped together. Rice BAC/PAC sequences that did not match any wheat sequence as well as redundant matches are omitted. The rice centromere location is indicated by `C'.