Upload
callia
View
29
Download
0
Tags:
Embed Size (px)
DESCRIPTION
Other Genome Projects. BIOL 473 Summer 2003. Why Other Genomes?. Proof of principle Refinement and advancement of technology “Relatively simple” data management Models of human disease Easy/inexpensive to culture/grow Many mutant strains/lines already identified. - PowerPoint PPT Presentation
Citation preview
Other Genome Projects
BIOL 473
Summer 2003
Why Other Genomes?
• Proof of principle
• Refinement and advancement of technology
• “Relatively simple” data management
• Models of human disease
• Easy/inexpensive to culture/grow
• Many mutant strains/lines already identified
Importance of Mutant Organismsin Identification of Gene Function
Mutant
Molecular Defect
Gene Function
Vertebrates
Rodent Genome Projects
• ~100 years of genetic research to support genomic findings
• Hundreds of mutant strains, well-characterized genealogies of common strains (esp mice)
• Evolutionary position relative to human:– Close: similar development, physiology & disease
– Divergent: conserved blocks of sequence suggest essential function
Rodent/Human Genome Comparison
• Extensive conservation of nucleotide sequences– Protein-coding regions (genes)– Small, noncoding intergenic regions (SNCIRs)
• Suggests unknown but important function, perhaps regional control of multiple gene expressions
• Extensive conservation of gene order (synteny)– MMU11 syntenic with HSA5 at 1 MB IL region: Perfect
correspondence of order, orientation, and spacing of 23 different genes
– Supports common ancestry– Suggests segmental rearrangement of chromosomes during
evolution
Zebrafish (Danio rerio)• Development rapid and transparent
• Easy to grow
• Dense map of genetic markers
• Many species-specific cell biology tools
– Including human gene transfer
– Including RNAi
– Including organogenesis pathways
• Significant synteny with human and mouse
• >90% similar set of genes with human
Fugu rubripes
PufferfishTetraodon nigroviridis
• Same gene information as humans in 1/8 DNA• Lacks many repeats• Very Small introns (many same ex/in struct)• 400 MY of gene sequence and order conservation• Control regions easy to detect: closer to genes/less nonconserved
intergenic region• 21 chromosomes all smaller than human 21
– Microchromosomes are gene dense
• Important for understanding– Unknown mechanisms of gene expression control– Chromosomal expansion– Function and persistence of “junk DNA”
Other Verts
• Salmon, sticklebacks, cichlids, and other commercial fish• Cats and Dogs
– Common diseases with humans– Important models of morphological variation– Important models of behavioral variation
• Chimpanzee– Mechanisms of pathogen resistance, incl HIV susceptibility– genetic changes crucial for evolution of Homo sapiens
• Agrispecies (cattle, horses; true for crops as well)– Whole genome sequencing prohibitively expensive– Partial genome sequencing and SNPS enhance decades of selective
breeding data• First nutria genome report appeared July 2002!!
– Kass & Doucet: Molecular Phylogeny of the Louisiana Nutria. Proc. LA Acad. Sci. 63:10-24.
The The Founders of Founders of
Nutria Nutria GenomicsGenomics
Why nutria?Why nutria?
Invertebrates
Why?
• Proof-of-principle: sequencing multi-cellular organisms
• Provide understanding of complex organismal functions
• Support decades of genetic research (esp with Drosophila)
Invertebrate Genome ProjectsInvertebrate Genome Projects
Genomic Surprises inDrosophila melanogaster & Caenorhabditis elegans
• Gene Expression anomalies– Ce: leader sequence transplicing
– Ce: polycistronic transcripts
– Dm: high variance in transcript length
– Dm: some distant regulatory sequences & long introns
• 50% more genes in Ce, despite complexity of Dm( # cells, # cell types, morphogenesis)
• Large gene families– Ce: steroid hormone-receptor gene family
– Dm: olfactory receptor gene family
• High conservation of major regulatory and biochemical pathways– some lost to parasitism in Ce
– Some novel to Dm due to complete morphogenesis
• RNAi highly effective in Ce: 90% gene knockout in 2/5 chromosomes
• Models for human disease: 50-60% human disease genes have Ce &Dm orthologs
• Models for drug development– Prozac resistance in Ce; ETOH tolerance in Dm
– No presumption that trait is same, but molecular interaction b/w gene products conserved even when they affect distinct processes
Plants
Arabidopsis thaliana• First plant genome sequenced entirety• 115Mb: about same size as D. melanogaster but 2X
genes (25,500)– Two rounds of whole genome duplication– Extensive chromosome reshuffling– Considerable gene loss after duplication– 1500 tandem arrays repeated genes (2-3 copies @)– Only 11,000 gene families minimum for complex
multicellularity
• 800 nuclear genes of plastid descent– Likely ongoing process– Plastid-targeting signal lost; now function in cyto
• 10% genome is novel miniature repeats (MITEs, MULEs)
Classes of Arabidopsis genes absent/underrepresented in animals:
• Enzymes for cell wall biosynthesis
• Transcellular transport proteins
– Minerals, organics, metabolites, toxins, macros
• Photosynthesis enzymes (rubisco, ETSs)
• Mediators of trophisms (turgor pressure, light, gravity sessility)
• Enzymes and cytochromes for secondary metabolites
• Many R genes (pathogen resistance); interspersed, not clustered
Classes of animal genes absent/underrepresented in Arabidopsis:
Ras G-protein family • Tyrosine kinase receptors • Nuclear steroid receptors
Other Plants Projects & Why?• Projects underway for 50 different species• Rice and Maize: small genomes, economically important
– Many commercial crops plants are polyploid, and genomes are too large to be feasibly sequenced in entirety
– Must rely on comparative genomics to support hybridization data– Rice and Arabidopsis show extensive but complex synteny
• Focus on QTLs rather than Mendelian (single-locus) traits– Resistance, flowering time, tolerance, sugar content, etc.
• Domesticated/wild relationships: maize vs. teosinte• Mutation/morphology relationships: Brassica oleracea
– Cabbage, kale, Brussels sprouts, broccoli, cauliflower, kohlrabi
• Support of classical genetics– Sweet pea, snapdragon
• Support of forestry (Poplar: small genome, easy to grow)– Lumber improvement (lignins, enzymes)– Biomass-biofuel improvment– Bioshperic carbon fixation
• Parent/Ecotype crop comparisons by comparative genomics