a purine-pyrimidine classification scheme of the genetic code

Jena

InstituteofMolecular Biotechnology

Swetlana Nikolajewa, Thomas Wilhelm Theoretical Systems Biology

Overview

The genetic code - introduction The new classification scheme of the genetic code shows:

symmetry characteristics explanation for the number (22) of tRNA genes in

mammalian mitochondrial genome amino-acids patterns and regularities of codons (strong,

mixed and weak codons) possible predecessors of our contemporary quaternary

triplet code

The Genetic Code

3 nucleotides bases (triplets) of A, G, C, U are used to code for 20 amino acids

two purines (A,G) two pyrimidines (C,U)

64 possible codons (4x4x4=43) 3 termination codons: UGA, UA(G/A) 61 codons for amino acid coding Met (AUG) codon is also the start codon

2nd base

U CA G

1stbase

U

UUU Phe UUC Phe UUA Leu UUG Leu

UCU Ser UCC Ser UCA Ser UCG Ser

UAU Tyr UAC Tyr UAA StopUAG Stop

UGU Cys UGC Cys UGA StopUGG Trp

UCAG

3rd base

C

CUU Leu CUC Leu CUA Leu CUG Leu

CCU Pro CCC Pro CCA Pro CCG Pro

CAU His CAC His CAA Gln CAG Gln

CGU Arg CGC Arg CGA Arg CGG Arg

UCAG

A

AUU Ile AUC Ile AUA Ile AUG Met

ACU Thr ACC Thr ACA Thr ACG Thr

AAU Asn AAC Asn AAA Lys AAG Lys

AGU Ser AGC Ser AGA Arg AGG Arg

UCAG

G

GUU Val GUC Val GUA Val GUG Val

GCU Ala GCC Ala GCA Ala GCG Ala

GAU Asp GAC Asp GAA Glu GAG Glu

GGU Gly GGC Gly GGA Gly GGG Gly

UCAG

The Common Genetic Code Table

The new classification scheme of the genetic code

binary representation of purines(A,G) → 1 pyrimidines(C,U) → 0

23 = 8 different binary triplets 000 , 001, … ,111each of these has again 8 possibilities, for instance: 000 stands for three pyrimidines: CCC, CCU, UUC, …, UUU 111 stands for three purines: GGG, GGA, GAA, …, AAA

C G binds via 3 hydrogen bonds in the complementary base-paring A U binds via 2 hydrogen bonds in the complementary base-paring

2nd base

U CA G

1stbase

U

UUU Phe UUC Phe UUA Leu UUG Leu

UCU Ser UCC Ser UCA Ser UCG Ser

UAU Tyr UAC Tyr UAA StopUAG Stop

UGU Cys UGC Cys UGA StopUGG Trp

UCAG

3rd base

C

CUU Leu CUC Leu CUA Leu CUG Leu

CCU Pro CCC Pro CCA Pro CCG Pro

CAU His CAC His CAA Gln CAG Gln

CGU Arg CGC Arg CGA Arg CGG Arg

UCAG

A

AUU Ile AUC Ile AUA Ile AUG Met

ACU Thr ACC Thr ACA Thr ACG Thr

AAU Asn AAC Asn AAA Lys AAG Lys

AGU Ser AGC Ser AGA Arg AGG Arg

UCAG

G

GUU Val GUC Val GUA Val GUG Val

GCU Ala GCC Ala GCA Ala GCG Ala

GAU Asp GAC Asp GAA Glu GAG Glu

GGU Gly GGC Gly GGA Gly GGG Gly

UCAG

The Common Genetic Code Table

The Common Genetic Code Table contains 64 fields…

Code Strong codons6 hydrogen bonds

Mixed codons5 hydrogen bonds


Weak codons4 hydrogen bonds

Pro CC (A/G)Proline

Ala GC (C/U)Alanine

Ala GC (A/G)Alanine

Leu CU (A/G)Leucine

Thr AC (C/U)Threonine

Thr AC (A/G)Threonine

Ser UC (C/U)Serine

Val GU (C/U)Valine

Val GU (A/G)Valine

Phe UU (C/U)Phenylalanine

Ile AU (C/U)Isoleucine

Ile/Met AU (A/G)Isoleucine/Methionine

000

001

100

101

Arg CG (C/U)Arginine

Cys UG (C/U)Cystein

His CA (C/U)Histidine

Tyr UA (C/U)Tyrosine

010

Arg CG (A/G)Arginine

Stop/Trp UG (A/G)Tryptophan

Gln CA (A/G)Glutamine

Stop UA (A/G)011

Gly GG (C/U)Glycine

Asp GA (C/U)Asparatic acid

Asn AA (C/U)Asparagine

110

Gly GG (A/G)Glycine

Glu GA (A/G)Glutamatic acid

111

Leu CU (C/U)Leucine

Leu UU (A/G)Leucine

Ser UC (A/G)Serine

Ser AG (C/U)Serine

Arg AG (A/G)Arginine

Pro CC (C/U)Proline

Lys AA (A/G)Lysine

The new classification scheme (standard genetic code)

the new scheme contains the same information in only 32 fields.





Pro CC (A/G)

Ala GC (C/U)

Ala GC (A/G)

Leu CU (A/G)1/2

Thr AC (C/U)

Thr AC (A/G)

Val GU (C/U)

Val GU (A/G)

Ile AU (C/U)

Ile/Met AU (A/G)5/0

001

100

101

Arg CG (C/U) Cys UG (C/U) His CA (C/U) Tyr UA (C/U)010

Arg CG (A/G) Stop /Trp UG (A/G)9/0

Gln CA (A/G) Stop UA (A/G)2/4

011

Gly GG (C/U) Asp GA (C/U) Asn AA (C/U)110

Gly GG (A/G) Glu GA (A/G)111

Leu UU (A/G)1/0

Ser UC (A/G)1/0

Ser AG (C/U)

Arg AG (A/G)6/6

Lys AA (A/G)3/0

Deviations from the Standard Code

Ser UC (C/U) Phe UU (C/U)000 Leu CU (C/U)1/1

Pro CC (C/U)

http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi

Mitochondrial Genomes Have Several Surprising Features

genetic code of mitochondria

only 22 tRNAs are required for mammalian mitochondrial protein synthesis





Pro CC (A/G)

Ala GC (C/U)

Ala GC (A/G)

Leu CU (A/G)

Thr AC (C/U)

Thr AC (A/G)

Val GU (C/U)

Val GU (A/G)

Ile AU (C/U)

Met/Met AU (A/G)

001

100

101


Arg CG (A/G) Trp /Trp UG (A/G) Gln CA (A/G) Stop UA (A/G)011



Leu UU (A/G)Ser UC (A/G)

Ser AG (C/U)

STOP AG (A/G) Lys AA (A/G)

The Mammalian Mitochondrial Genetic Code

Ser UC (C/U) Phe UU (C/U)000 Leu CU (C/U)Pro CC (C/U)

http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi





tRNAIle AU (C/U)

tRNAMet AU (A/G)

001

100

101

tRNACys UG (C/U) tRNAHis CA (C/U) tRNATyr UA (C/U)010

tRNATrp UG (A/G) tRNAGln CA (A/G) STOP UA (A/G)011

tRNAAsp GA (C/U) tRNAAsn AA (C/U)110

tRNAGlu GA (A/G)111

tRNALeu2 UU (A/G)

tRNASer2 AG (C/U)

STOP AG (A/G) tRNALys AA (A/G)

The Mammalian Mitochondrial Code: 8 tRNAs for family codons + 14 tRNAs for non-family codons

tRNASer1 UC

tRNAPhe UU (C/U)000tRNALeu

1 CUtRNAPro CC

tRNAAla GC

tRNAArg CG

tRNAGly GG

tRNAThr AC tRNAVal GU

http://mamit-trna.u-strasbg.fr/2DStructures.html





Pro CC (A/G)

Ala GC (C/U)

Ala GC (A/G)

Leu CU (A/G)

Thr AC (C/U)

Thr AC (A/G)

Ser UC (C/U)

Val GU (C/U)

Val GU (A/G)

Phe UU (C/U)

Ile AU (C/U)

Ile/Met AU (A/G)

000

001

100

101


Arg CG (A/G) Stop/Trp UG (A/G) Gln CA (A/G) Stop UA (A/G)011

Gly GG (C/U) Asp GA (C/U)Asparatic acid


110

Gly GG (A/G) Glu GA (A/G)Glutamatic acid

111

Leu CU (C/U)


Ser AG (C/U)

Arg AG (A/G)

Pro CC (C/U)

Lys AA (A/G)Lysine

Amino acids patterns: Polar requirement of NCN and NUN codons

C. R. Woese, G. J. Olsen, M. Ibba, D. Söll Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process. MMBR 2000(64) 202-236





Pro CC (A/G)

Ala GC (C/U)

Ala GC (A/G)

Leu CU (A/G)

Thr AC (C/U)

Thr AC (A/G)

Ser UC (C/U)

Val GU (C/U)

Val GU (A/G)

Phe UU (C/U)

Ile AU (C/U)

Ile/Met AU (A/G)

000

001

100

101





Leu CU (C/U)


Ser AG (C/U)

Arg AG (A/G)

Pro CC (C/U)

Lys AA (A/G)

Amino acids patterns: Hydrophobicity.

Kyte&Doolittle, 1982, http://biology-pages.info

http://biology-pages.info/

http://biology-pages.info/





Pro CC (A/G)

Ala GC (C/U)

Ala GC (A/G)

Leu CU (A/G)

Thr AC (C/U)

Thr AC (A/G)

Val GU (C/U)

Val GU (A/G)

Ile AU (C/U)

Ile/Met AU (A/G)

001

100

101






Ser AG (C/U)

Arg AG (A/G) Lys AA (A/G)

Codon-Anticodon symmetry

Ser UC (C/U) Phe UU (C/U)000 Leu CU (C/U)Pro CC (C/U)





Pro CC (A/G)

Ala GC (C/U)

Ala GC (A/G)

Leu CU (A/G)

Thr AC (C/U)

Thr AC (A/G)

Ser UC (C/U)

Val GU (C/U)

Val GU (A/G)

Phe UU (C/U)

Ile AU (C/U)

Ile/Met AU (A/G)

000

001

100

101





Leu CU (C/U)


Ser AG (C/U)

Arg AG (A/G)

Pro CC (C/U)

Lys AA (A/G)

Point symmetry

D. Halitsky Extending the (Hexa-)Rhombic Dodecahedral Model of the Genetic Code: the Code's Four 6-fold Degeneracies and the Ten Orthogonal Projections of the 5-cube as 3-cube. Computer Systems Technology 2004

Correlation of codon strength and amino acid properties Measure Strong codons Mixed codons Weak codons

Dinucleoside monophosphates

Hydrophilicity (Weber & Lacey 1978) 1.686 1.434 1.235

Hydrophilicity (Barzilay et al. 1973) 2.72 2.26 2.26

Hydrophobicity (Garel et al. 1973) 2.556 3.413 3.982

Amino acids

Molec. Weight (Handbook value) 907 1065.6 1217.5

Molec. Volume (Grantham 1974) 381 637.5 906

Refractivity (Jones 1975) 83.86 140.03 186.51

Alpha pK1 (Zimmermann et al. 1968) 16.96 17.11 17.43

Bulkiness (Zimmermann et al. 1968) 93.22 124.345 143.54

Specific volume (McMeekin et al. 1964) 5.26 5.37 5.8

Polarity (Zimmerman et al. 1968) 107.16 109.58 58.14

Polarity (Woese et al. 1967) 61.2 59.15 51

Polarity (Grantham 1974) 71.2 67 56.3

Hydrophobicity (Jones 1975) 9.18 8.385 16.93

Hydrophobicity (Levitt 1976) -2.2 1.6 8.8

Hydrophobicity (Bull & Breese 1974) 3880 -165 -6790

Hydrophilicity (Weber & Lacey 1978) 7.02 6.585 5.59

Partition coefficient (Garel et al. 1973) 1.88 5.58 7.6

Sequence Frequency (Jungck 1971) 4280 3522 2966

Evolution of the genetic code

binary doublet: 41=4 fields

00 00 00 00

01 01 01 01

10 10 10 10

11 11 11 11

00* 00* 00* 00*

01* 01* 01* 01*

10* 10* 10* 10*

11* 11* 11* 11*

quaternary doublet code: 42=16 fields

our contemporary code is the quaternary triplet code: 43=64 fields

00

01

10

11

CGU, UAC,…

CGU, UAC,…





Pro CC (A/G)Proline

Ala GC (C/U)Alanine

Ala GC (A/G)Alanine

Leu CU (A/G)Leucine



Ser UC (C/U)Serine

Val GU (C/U)Valine

Val GU (A/G)Valine




000

001

100

101


Cys UG (C/U)Cystein



010




Stop UA (A/G)011

Gly GG (C/U)Glycine



110

Gly GG (A/G)Glycine


111

Leu CU (C/U)Leucine

Leu UU (A/G)Leucine

Ser UC (A/G)Serine

Ser AG (C/U)Serine


Pro CC (C/U)Proline

Lys AA (A/G)Lysine

Evidence: Evolution of the Genetic Code

Outlook Looking for binary patterns in the

genomes

Acknowledgment

Additional information

Thank you for your attention !

http://www.imb-jena.de/~sweta/genetic_code/

Maik Friedel Andreas

Beyer Frank Grosse





Pro CC (A/G)Proline

Ala GC (C/U)Alanine

Ala GC (A/G)Alanine

Leu CU (A/G)Leucine



Ser UC (C/U)Serine

Val GU (C/U)Valine

Val GU (A/G)Valine




000

001

100

101


Cys UG (C/U)Cystein



010




Stop UA (A/G)011

Gly GG (C/U)Glycine



110

Gly GG (A/G)Glycine


111

Leu CU (C/U)Leucine

Leu UU (A/G)Leucine

Ser UC (A/G)Serine

Ser AG (C/U)Serine


Pro CC (C/U)Proline

Lys AA (A/G)Lysine

The new classification scheme of the standard genetic code

T.Wilhelm, S.Nikolajewa A new classification scheme of the genetic code. J. Mol. Evol. (2004) 59: 598-605

http://www.imb-jena.de/~wilhelm/jme2004.pdf

a purine-pyrimidine classification scheme of the genetic code

Documents

genetic code shows

aaa c g binds

uag stopugu cys ugc

termination codons

uaga61 codons

pyrimidines c

u binds

regularities of codons