Download Lessons for biocomputing from Salzberg, Chpt 1

Organisms are made up of cells, cells are largely protein
and DNA carries the instructions for the synthesis of those
proteins
DNA is made up of subunit building blocks called
nucleotides
Nucleotides are joined into chains and two such chains
associate with eachother by base pairing
The sequence information in DNA is copied into RNA
(mRNA) which then directs protein synthesis
Amino acid assembly during translation occurs on
ribosomes; tRNA serves as the crucial adaptor molecule
Proteins are composed of subunits called amino acids;
mRNA directs the synthesis of an amino acid polymer
Rare mutations in DNA are changes in its nucleotide
sequence, leading to an altered mRNA and an altered
protein
A brief overview of the human genome
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Size = 3x109 base pairs (bp), A paired with T and G paired with C,
distributed over 23 chromosomes (this is for a haploid, or germ cell;
double those numbers for a diploid somatic cell)
Nucleotide changes occur in DNA via mutations; the spontaneous
mutation rate is approx. 10-8 per germ cell per year
Base composition: 40% GC base pairs; less than 2% in the format
CpG; this is b/c of mutation at such sites, CpG -> TpG, especially so
when C is methylated
Genic content of our genome: 3-5% of genome = “genes”; this
represents about 1.5x107 bp and includes approx. 40,000 genes
What’s in the remaining 95% of the genome? About 40% is
retroelements, remnants of retroviruses (much like computer viruses).
Retroelements are usually highly methylated at the C in CpG doublets
About 30% of the genome = variable, simple repeat sequences in DNA
Genes include both coding regions as well as control
regions
Consensus sequences identify evolutionarily conserved
sequences that are likely to be important; eg, the
promoter
Overview of the Prokaryotic Promoter Region
Promoter
-10
TATAa
Met
+1
ATG
Eukaryotic Promoter Structure
Met
TATAaA
-30
A
+1
ATG
ACCATGG
+50
Alternative promoter structures
Initiator (Inr)
CpG Islands
YY A N T/A YYY
+1
(CpG)20-50-----+1
Some general landmarks that characterize transcription
and translation
Short, conserved sequences delimit exon/intron
boundaries
Genomic DNA
cDNA
mRNA
aa1-aa2-aa(n)
TATAa……..ATG
Start
GU………AGGG
Intron (n)
G GU…..AGG
Intron #1
UAA
UAA……..AAUAAA
STOP
Poly A tail
Repetitive DNA sequences comprise much of the noncoding segment of the genome
30%
1-3%
A brief overview of the human genome






Size = 3x109 base pairs (bp), A paired with T and G paired with C,
distributed over 23 chromosomes (this is for a haploid, or germ cell;
double those numbers for a diploid somatic cell)
Nucleotide changes occur in DNA via mutations; the spontaneous
mutation rate is approx. 10-8 per germ cell per year
Base composition: 40% GC base pairs; less than 2% in the format
CpG; this is b/c of mutation at such sites, CpG -> TpG, especially so
when C is methylated
Genic content of our genome: 3-5% of genome = “genes”; this
represents about 1.5x107 bp and includes approx. 40,000 genes
What’s in the remaining 95% of the genome? About 40% is
retroelements, remnants of retroviruses (much like computer viruses).
Retroelements are usually highly methylated at the C in CpG doublets
About 30% of the genome = variable, simple repeat sequences in DNA
Gene identification can begin with mRNA isolation and
formation of copy DNA (cDNA)
Large-scale gene analysis can be performed using DNA
microarrays, or chips
Human CF gene, approx. 250kb
4kb
Approx. 1 mutation per 1kb in noncoding regions;
if 80% of the genome is noncoding:
3x109bp x 0.8 = 2.4x109 x 1/1,000 = 2.4x106 mut.
differing between any two individuals