Python Programming for Biology: Bioinformatics and Beyond

bacteria and organelle genomes (e.g. mitochondria and chloroplasts).

Codon

positions

Amino acid translation or stop

Codon

positions

Amino acid translation or

stop

1st

2nd

3rd

One-

letter

code

Three-

letter

code

Full name

1st

2nd

3rd

One-

letter

code

Three-

letter

code

U

U

U

F

Phe

Phenylalanine

A

U

U

I

Ile

U

U

C

A

U

C

U

U

A

L

Leu

Leucine

A

U

A

U

U

G

A

U

G

M

Met

U

C

U

S

Ser

Serine

A

C

U

T

Thr

U

C

C

A

C

C

U

C

A

A

C

A

U

C

G

A

C

G

U

A

U

Y

Tyr

Tyrosine

A

A

U

N

Asn

U

A

C

A

A

C

U

A

A

STOP

A

A

A

K

Lys

U

A

G

A

A

G

U

G

U

C

Cys

Cysteine

A

G

U

S

Ser

U

G

C

A

G

C

U

G

A

STOP

A

G

A

R

Arg

---

U

G

G

W

Trp

Tryptophan

A

G

G

C

U

U

L

Leu

Leucine

G

U

U

V

Val

C

U

C

G

U

C

C

U

A

G

U

A

C

U

G

G

U

G

C

C

U

P

Pro

Proline

G

C

U

A

Ala

C

C

C

G

C

C

C

C

A

G

C

A

C

C

G

G

C

G

C

A

U

H

His

Histidine

G

A

U

D

Asp

C

A

C

G

A

C

C

A

A

Q

Gln

Glutamine

G

A

A

E

Glu

C

A

G

G

A

G

C

G

U

R

Arg

Arginine

G

G

U

G

Gly

C

G

C

G

G

C

C

G

A

G

G

A

C

G

G

G

G

G

An  important  complication  to  the  way  in  which  RNA  transmits  its  sequence  message

comes  from  the  fact  that  it  usually  has  large  non-coding  sections  removed  before  it

becomes  a  mature  mRNA  and  its  sequence  is  translated  into  protein.  The  regions  of  an

RNA chain that are removed are called introns and those that remain are called exons. The

RNA is said to be spliced: the ends of the exons are joined as the introns are lost. Introns

are  very  common  in  the  human  genome  and  their  presence  makes  it  significantly  more

difficult to detect which bits of a gene are actually used to make protein sequences.

Even  though  DNA,  RNA  and  protein  really  are  sequences  of  chemical  compounds,

linked together into a chain, it is often sufficient to represent them simply as a sequence of

letters or residue codes. You can perform many useful analyses simply by knowing what

the order of amino acids or nucleotides is, without having to consider all of the atoms that

are present in the real molecule.

---

DNA sequencing

Today  the  majority  of  the  sequence  information  for  DNA,  RNA  and  protein  in  various

organisms  comes  from  the  sequencing  of  just  DNA.  Because  of  the  rules  of  nucleotide

pairing and because of the genetic code (three nucleotides give one amino acid) it is easy

to determine an RNA and protein sequence once you know the gene-coding regions in the

DNA. It may be difficult to work out where the coding regions of a gene start and end in a

large section of DNA, but the conversion to the different types of sequence is trivial.

DNA is sequenced with a special kind of chemical reaction, which these days is often

performed by a computerised machine. In essence many copies of a DNA strand are made

using  an  enzyme  (a  protein  that  catalyses  the  required  chemical  reaction),  and  the

nucleotides that are added to the end of the growing strands are detected. A common way

(used in Sanger and Illumina sequencing methods) of detecting the nucleotide added is to

have  the  reaction  occasionally  stop,  when  an  inhibiting  compound  is  incorporated  at  the

growing  end.  Here  there  are  four  different  inhibitors  that  take  the  place  of  each  of  the

DNA nucleotides. The aim is to get some of the copied DNA strands to stop growing at

every  single  nucleotide  position.  The  sequence  is  revealed  by  detecting  which  inhibitor

stopped  the  chain  growing  at  each  position;  i.e.  which  nucleotide  is  at  the  end  of  each

length  of  strand.  The  different  inhibitors  at  the  end  of  the  DNA  strands  are  designed  to

glow  with  different  colours  to  make  them  easy  to  identify.  The  reaction  can  happen  in

distinct  cycles  (e.g.  Illumina  method)  to  give  subsequent  nucleotide  reads,  or  the  DNA

strands  can  be  sorted  by  size  so  that  the  end  nucleotide  can  be  detected  afterwards  (the

Sanger method).

The  actual  DNA  that  is  used  in  the  sequencing  reaction  commonly  comes  from  an

organism’s set of chromosomes (which collectively are referred to as a genome), but it is

also  possible  to  have  DNA  which  comes  from  the  amplification  of  a  small  section  of  a

genome  (i.e.  a  small  quantity  is  copied  to  give  a  large  amount)  or  to  use  DNA  that  has

been  copied  from  RNA  (i.e.  opposite  to  the  usual  flow  of  information)  using  a  special

enzyme.