Heaphy 12 Genomics Flashcards
Genomics:
study of genomes and genome sequences
first use by Hans Winker in 1920- All the genes in a haploid set. Modern usage encompasses all the cellular DNA in an organism
term genomics was coined by
Thomas Roderick for mapping sequencing and characterising genomes
1986
Genomics Scope:
Viral genomics, Archaeal, Bacterial, (prokaryotic), Eukaryotic.
Species genomics, mouse, human…, mammalian, avian….,organellar,
Metagenomics:
soil water ocean, human, gut, mouth, teeth,skin, object or surface such as a shower curtain.
DNA sequencing
Sanger di-deoxy sequencing 1980 to date, human genome sequence, technological improvements, very accurate long sequences but relatively slow and expensive. 1000s of nucleotides per day, genomes in months or years
DNA sequencing
capillary fluorescence:
Much faster, machine read
and filed straight to a computer in the 1990s
DNA sequencing
radioactive gel-based:
Slow, manually read in the 1980s
next generation sequencing:
2007 + , Illumina, Roche 454, ion torrent and many more technologies, short sequences, less accurate but massively parallel, millions to billions of nucleotides per day, genomes in minutes or overnight. Technology still developing
Shotgun sequencing
Genome assembly relies on identifying overlapping sequences
Human genome
3 billion base pairs 23 chromosome pairs
first sequenced gene
bacteriophage MS2 coat protein gene 1972
first sequenced genome
bacteriophage MS2, 3569 nts 1976, RNA genome
first sequenced DNA genome
bacteriophage fX174, 5368 nts 1977
first bacterial genome
Haemophilus influenzae, 1,830,140 nts 1995
first eukaryotic sequence
S. cerevisiae, 12,495,682 in 1996
Human genome sequence reported
~3.3 billion nts in 2003
Largest genome sequence
loblolly pine, 22.18 billion
Nucleotides
Genome sizes
E.coli 5Mb
S. cerevisiae 12.5 Mb
H. sapiens 3.3GB
Genome sizes from graph
Viroids, 300 nts; viruses 3.5Kb-2.5Mb; bacteria and archaea 150Kb-10Mb;
eukaryotes 13Mb-22Gb. Free living organisms have larger genomes than
Endosymbionts. Overlap in genome sizes between domains
Microbial
General features of genomes: Size form protein coding regions operons RNAs gene transfer evolving
- Small
- Circular & plasmids
- Gene density high >90% (short intergenic regions, introns rare, little repetitive/ non-coding seq)
- Protein coding regions short <1Kb
- Operons w/ proctor just upstream
- few non-coding RNAs
- Frequent horizontal gene transfer
- rapidly evolving
Eukaryotic
General features of genomes: Size form protein coding regions operons RNAs gene transfer evolving
- Large Gb
- linear chromosomes
- gene density low <25% (long intergenic regions, introns common, repetitive non-coding seq common)
- Protein coding regions larger, 30Kb +
- Average of 3 splice variants
- many non-coding RNAs
- Infrequent HGT
- Less rapid evolution?
What can genomics do ?
- everything about an organism and its developmental program
Metabolic capabilities. - Phylogeny: position in the tree of life
-Disease resistance or susceptibility - understand what life is, to create and manipulate it
- Metagenomics: how an ecosytem functions and an organisms role in that ecosystem
importance of bioinformatics
Individuals & populations:
DNA-> RNA ->protein -> phenotype -> selection -> evolution
Computational goals of bioinformatics:
- Learn & generalise: conserved patterns
- Prediction
Organise & intergrate: systematic & genomic approach
-Simulate: model gene expression
-Engineer: construct
-Target: mutations, drugs
Discovering function from protein sequences:
- active site of trypsin- like serene proteases: GDSGG
- zinc finger
- structure/function
- sequence similarity
Genomic analysis
describes the whole organism, bioinformatics and experimentation allows us to identify individual components and to determine their functions. Development of bio building blocks enables the construction of new organisms with different properties
Interactomes:
can be inferred from bioinformatic and biochemical data, redrawn as engineering circuit diagrams which facilitates biological design
Craig Venter
Bacterial genomes and bacteria reduced to chemistry.
1.08Mb Mycoplasma mycoides bacterial genome similarly synthesized from chemicals, reassembled in yeast and transplanted into Mycoplasma capricolum in 2010.
Lessons from Genomics
Prokaryotic cell <500 genes M. genitalium
Free living prokaryote ~1500 genes Aquifex aeolicus
Solibacter usitatus 10. Mb genome 10 000 genes (largest)
Free living eukaryote ~5000genes S. pombe and cerevissae
15000 genes multicellular organism Drosphila C.elegans
Human consciousness 20 000 genes
Distinction between prokaryote cell and eukaryote cell is one of gene type and organisation and interaction- NOT NUMBER OR GENOME COMPLEXITY
Transcriptosome
What genes expressed when, how much and in response to what.
Proteome
What proteins expressed, when, how much, in response to what.
Metabolome
Glycome
interactome
Comparative genomics
What is conserved between species?
Genes for basic processes
Understand the uniqueness between different species their adaptive traits
What makes closely related species different?
Analyzing & comparing genetic material from different species to study evolution, gene function, and inherited disease
Sequence individual genomes
improved disease diagnostics and personalised therapies. Possible, becoming routine.
