Topics in Bioinformatics

CS832b

Bin Ma

Lecture 1: Basic

Three molecules we will study

• DNA• A string over alphabet {A,C,G,T}

• RNA• Primary structure – a string over alphabet {A,C,G,U}

• Secondary and tertiary structures

• Protein• Primary structure – a string over alphabet

{A,R,N,D,C,Q,E,G,H,I,L,K,M,F,P,S,T,W,Y,V}

• Secondary and tertiary structures

5’

5’ 3’

3’

DNA

5’…AGTAGCCTATGCGA…3’ …::::::::::::::…3’…TCATCGGATACGCT…5’

5’…AGTAGCCTATGCGA…3’

>CHRXGATCACCTGACATCAGGAGTTCAAGACCAGCCTGCCAACGTGGTGAAACCCCATCTCTACTAAAAATAGGAAATTCACCTGGTGGCAGGTGCCTGTAATCCCAGCTACTCGGGAGGCTGAGGCAGAAGAATCGCTTGAACCCAGGAGGTGGAGATTGCACTGAGCTGAGATCACGCCACTGCGCTCCAGCCTGGGTGACAGAGCAAGACTCCATAAAAAAAAAAATTATAACCTAATGATTAAATACTGTAGGGAAGAGCTTACCACAATTGCTGGCCCATGGCCAATGCTGGGTATAAGACAGCTACTGCAAACAACCATGATGATGATACATCTCTTGTGTAGGGTTAGGTTGTTTGAGACACATTCTATGCTCCTTGATTTGATTGGAAGGTACCTTGGTTCCTTGGGGACTTGGAGGTGACGAAAGCCTCCCTGGGGACAAAACTCACCTTCACTTCTCTAATATCAAGCTTCAGCAACCTGCTCCAGCTACAGCACAGGGTTGGACAGGCCCAACAACAGAGGAAATCCACAAAGTGTGTCTTGACACATACATCCACGGGGTCTAACGAGGTGAGGCCAATGACTGCTTCCACACACCCCAGCCAGACTCTGACTTCACTCCCGGCAGGTTTCAGTAGACTTGGCAGCAGTTGGAGCGAGCTGGCTTCTTGCGGTAGGCAGCCATGTTGGAAGAGCTCCCAATAGTCCTCGTTTCCTGGTAATCTCATGCTTGGATCATCTTCTTCTCTTGAGTGAAGAGAAGAACTGCAGAGAGAGACAGAGACAGAGAGACAGATCACAGGGGCAGTTTCCCCCATACTGTTCTCAAGATAAATGAGTCAACTCTTACACCTCTTTTCTCTGGTGTAAAACAAGGCTGGTGAACAGGCAGAGAGAACTGGGGTGTTGGAGTAGCATTGACCTTCCTTCTTCATCCCTCTATAATCTCTCCTAGTGCAGGAGTAGGAAAACTAAAAATCACACGTCTGATCATCTGTGATCTCAGAGTCTTGGACAAGCCTTGCTTGCCAATCAGCAGGGATGGGAGTTGGAGCCATCTCCAAGTGTCCCCCCACAAATCTATGTCCACCTGGAAGTTTCAAATGCAACTTTATTTGGGAAAGGCAATTTTGCAAATGTTATTAAGTGAAGGATCTAGGGATGAGATCATCCTGGAGTAGGGTGGGTCCTAGGTCAAATGACAGGAAATCTGCCCACCTCGGCCTCCCAAAGTGCTGGGATTACAGGCATGAGCCACCAAACCTGGCCTATCATTGATTTAATGATTAATACGGTTAGGCTCTGTGTCCCCACCCAAATCTCATCTCAAATTGTAATTCCCATGTGTCCAGGGAGGGAGCTTGTGGAAGGTGATTGGATCACAGGGGCAGTTTTTGTCATGCTGTTCTCATGATAAATGAGTCAATTCTCAGAAGAGATGATGGTTTTAAAGTGTGGCACTTCTTTGCTCTCTTGCTCTCTCTCTCTCCTGAGTAGACTGGCTCATTCTTTCTACTGGTTACAAGCAATAGAAGTGATAACAAAATTGATGGTTTCTCATTTCCTAAATGGTACCAGTGGATTCCTGGTTTCCTCTCTCTCTCTTCTCTCTCTCTATCAACTTTTCCCTCAATCTCTCTATCAACCTCCCTCTCTCTCAATCTCAATCTCTCTCAGTCTCATTCTCAATCTCTTTTGCTCAATCTCTTTCTCAGCTTCTCTCCCTCAATTTCTCTTTTGCAACTTCTCTCTCTCAGTCTGTGTCTCTCAATCTCCCTCTCTCAATCTCTCTTGTAGTCTCCCTGTCTCTCATACTCTCTCTGTTTCTGTCTGTCTCTGCCCTTGCTCTAGGGAAAGCAAGTTCTTATGCTGTAAGTTCTCCTGTAAAAAGGTCCACATGATACGGAACTGGCCATCTTTGGCCAACATGAGTGAGTTTAGAAGTGTGCCTTTCACCAGTTGAGCCTTCAAATGAGATCCCAGCCCTGGATGACACAGTGACAGTAACCTGCTAGGAACTGTGAACCAGAGGCACCCAGCCAAGCTGCTCCCAGACTCCCAACCCAGTGAAACCATAAGATAATAAATGCATGTTGTTTTAAGCTGCTAAGTTTGGGGGTCACTTGTTACACAGCAACAGCTGACTCATACATTTTCTTTGAAATTGATTTCCACTTCTGTCACCAGCATCATTCCATAAATTTGCTCTATGTGCATTGCTGACCTGCAGTAGAAGTTTTGGAGAAGTGAACCACATCCCCTTATCTGCCATTTGACAGCAAGCAGCCTCAAACATTCATAATTTCTTTCCTGACTCTCCACTCCACACTGTTGCCTGCCTTCCTGGTTCCAGATCTTTGGATCTGGACTGACACCTGGGCACTGTCATAGGCATCCGTGTGAAGAGACCACCAACAGGCTCTGTGTGAGCAATAAAGCTTTTTAATCACCTGGGTGCAGGTGGGCTGATTCTGAAAAGAGAGTCAGCAAAGAGTGGTGGGATTATCATTAGTTCTTATAGGTTCGGGATAGGTGGTGGAGTTAGGAGCAATTTTTTGTGGGCAGGGAGTGGATCTTACAAAGGACATTCTCAAGGGTGGGGATGATTTTACAAAGTACCTTCTTAAGGGCGGGGGAGGATATTACAAAGTACCTTCTCAAGGGTGGGGATGATTTTACAAAGTACCTTCTTAAGGGCGGGGGAGGATATTACAAAGTACCTTCTCAAGGGTGGGGGTGGATATTACAAAGTACCTTCTTAAGGGCAGGGGAGGATATTACAAAGTACCTTCTCAAGGGGGGGGATGATTTTACAAAGTACCTTCTTAAGGGCGGGGGAGGATATTACAAAGTACCTTCTCAAGGGTGGGGGTGGATATTAGAAAGTACCTTCT

• Chromosome X is one of the 23 chromosomes in human genome.• Chromosome X has 162 million base pairs.

Genome Sizes

Species Size in bps

Amoeba dubia 670,000,000,000

Homo sapiens 3,400,000,000

Drosophila melanogaster 180,000,000

Mycoplasma genitalium 580,000

Human immunodeficiency virus type 1

9,750

Protein and Amino Acids

Protein

Protein

GOT Ecoli

A protein sequence

>gi|7228451|dbj|BAA92411.1| EST AU055734(S20025) corresponds to a region …

MCSYIRYDTPKLFTHVTKTPPKNQVSNSINDVGSRRATDRSVASCSSEKSVGTMSVKNASSISFEDIEKSISNWKIPKVN

IKEIYHVDTDIHKVLTLNLQTSGYELELGSENISVTYRVYYKAMTTLAPCAKHYTPKGLTTLLQTNPNNRCTTPKTLKWD

EITLPEKWVLSQAVEPKSMDQSEVESLIETPDGDVEITFASKQKAFLQSRPSVSLDSRPRTKPQNVVYATYEDNSDEPSI

SDFDINVIELDVGFVIAIEEDEFEIDKDLLKKELRLQKNRPKMKRYFERVDEPFRLKIRELWHKEMREQRKNIFFFDWYE

SSQVRHFEEFFKGKNMMKKEQKSEAEDLTVIKKVSTEWETTSGNKSSSSQSVSPMFVPTIDPNIKLGKQKAFGPAISEEL

VSELALKLNNLKVNKNINEISDNEKYDMVNKIFKPSTLTSTTRNYYPRPTYADLQFEEMPQIQNMTYYNGKEIVEWNLDG

FTEYQIFTLCHQMIMYANACIANGNKEREAANMIVIGFSGQLKGWWNNYLNETQRQEILCAVKRDDQGRPLPDRDGNGNP

TELKEGFHMEEKDEPIQEDDQVVGTIQKYTKQKWYAEVMYRFIDGSYFQHITLIDSGADVNCIREDEILDQLVQTKREQV

VNSIYLHDNSFPKSMDLPDQKITEKRAKLQDIPHHEERLLDYREKKSRDGQDKLPMEVEQSMATNKNTKILLRAWLLST

A protein sequence may have a few hundreds to several thousands amino acids.

RNA

Animal cell

Nucleus

Chromatin

Mitochondrion

Nucleolus (rRNA synthesized)

Plasma membraneCell coat

Cytoplasm

Protein synthesis

Protein synthesis

Genetic code ..ATTCACAGTGGA..

I

H

S

G

Notes on translation

• Reading frame• Start and end codon

• Third base not important

• 5’ -> 3’

DNA replication

The Central Dogma of Molecular Biology

DNA RNA Proteintranscript translation

replication

genotype phenotype

Exception – retroviruses

DNA RNA Proteintranscript translation

replication

genotype phenotype

ProteinPhenotype

DNA(Genotype)

Biology

Genes• One gene encodes one protein (or sometimes

RNA).• Like a program, it starts with start codon (e.g.

ATG), then each three code one amino acid. Then a stop codon (e.g. TGA) signifies end of the gene.

• Genes are dense in prokaryotes and sparse in eukaryotes.

• In the middle of a eukaryotic gene, there are introns that are spliced out (as junk) after transcription. Good parts are called exons. This is the task of gene finding.

Introns and Exons

Jumping genes

• Genes can jump over other genes.

Gene related diseases

• Hemophilia: on X chromosome.• Sickle-Cell Anemia: single nucleotide mutation in the first

exon of beta-globin gene (removes a cutting site). 1 in 12 African Americans are carriers. (sick for homozygotes)

• BRCA1 gene (chr. 17q) – responsible for ½ inherited breast cancer (10% of breast cancer)

• Fragile X syndrome (mentally retard) – 1 in 1250 males, 2500 females (dominate, but females have partially expressed good gene). FMR-1 gene: tri-nucleotide repeats >200 causes disease.

• P53 gene: chr. 17p, responsible for ½ of all cancers