Arginine as an evolutionary intruder into protein synthesis

BIOCHEMICAL

Vol. 53, No. 3,1973

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ARGININE AS AN EVOLUTIONARY INTRUDER INTO PROTEIN SYNTHESIS

Thomas

Space Sciences of California,

University

Received

June

H. Jukes Laboratory Berkeley,

Calif.

94720

4, 1973

SUMMARY The arginine content of proteins is, on the average, far less than would be anticipated from the fact that 6 of the 61 codons for amino acids in the genetic code are for arginine. In contrast, lysine is more abundant than would be expected from its 2 codons. It is suggested that arginine replaced ornithine in protein synthesis during the evolution of the genetic code. The frequency is not

uniform,

between

and it

The with

distribution

of codons

responsible

basicity

preferentially

Subak-Sharpe

which

et al

organisms is

present

some extent

except

for

the

the amino

than noted

as indicating in four

rejected

reasons

acid

It

arginine

in evolution.

Copyright @ 1973 by Academic Press, Inc. All rights of reproduction in any form reserved.

that

a selective codons. It

The

709

was compared (1969).

an anticipated

are

primarily

that

lysine

l),

despite

basicity

lysine

(pK13

is

appears

fact

of arginine = 10.5).

against

Apparently,

used the

of CpG in the

process

therefore

such divergences.

case of arginine,

with

(Table

each

from

and Jukes

that

the scarcity

for

proteins

appears

of

codons

conspicuous

has 6.

correlation

for

by King

acids

in proteins

divergences

of 4.2% as compared

and arginine

(1966)

a fair

in 53 vertebrate amino

acids

of

to explore

proteins.

is much greater

is

number

in most proteins

has 2 codons

= 12.5)

certain

in

there

and the

each

are

to arginine

lysine

(PK'~

for

and lysine

for

that

amino

the possible

acids

to the extent

Arginine

different

of interest

was found

was present

10.7%.

is

of amino

A good correlation

that

It

acids

and to examine

the number

which

of amino

code.

correlation,

of the

has been noted

the abundance

in the genetic this

of occurrence

DNA of

this

arginine that

doublet, is

the

to concept

Vol.53,No.3,1973

that

"all

BIOCHEMICAL

is

for

the best

AND BIOPHYSICAL

in this

best

possible

RESEARCH COMMUNICATIONS

of all

codes"

may not

be

valid. Perhaps the

arginine

tRNAs for

code.

This

entered

another might

amino

happen

aminoacyl-ligase

system

enzyme chemistry

is

containing

formation

gives

ornithine

for

(homo-ornithine) purposes

might

system

in preference

functions.

in Table

The codons

further

would

to arginine

The proteins

lysine

for

important

in

the

statistical

a single

variable assumed

tend

or specificity

parameter number

are

chain. (S)

to arginine

into

replacing

affinity

than

proteins

could

at the same time, than

lysine

arginine amino

codons

for acid,

for

many ornithine.

such purposes

shown

lengths

and have different

the proportion

in Table

of arginine

and this

(Hill

et al,

1966).

containing

in which

The chains.

and constant from

chain

led

is

The

in arginine

results

of codons,

proteins

descended

The heavy

the

is

pathway.

resulted

lysine

1 are of varying

to have

as a molecule

with

acid,

1962).

and similar

to select

in

1.

and

shown without

treatment.

polypeptide

duplication

missing

tRNA-

dihydrofolic

of arginine but,

genetic

antagonists

have

have

more acceptable

the

acid

had a stronger

advantages,

codons,

total

The imnunoglobulins for

then

could

the

metabolic

would

arginine

have been

for

the

of such a phenomenon

a regular

The entry

special

as a substitute

The living

This if

tRNA.

certain

in

by charging

from

affinity

and Jukes,

evolution

synthesis

displaced

substrate,

(Delmonte

during

synthesis

of folic

the normal

arena.

ornithine

conveyed

affinity

to arginine

the biochemical in protein

have

rise

was thus

An example

greater than

of protein

had a high

in question.

pathway

ornithine

which

arginine

reductase

of this

entering

if

group

dihydrofolic

Ornithine

acid,

the far

a 4-amino

has for

the mechanism

a single

has an S region

of about

710

light

are

These

common ancestral this,

the

contain regions

protein light

of approximately the

responsible

and heavy,

(C) regions.

Following

S and C regions

two genes

same length

chain equal as that

are

by gene evolved length. of the

Vol.

53, No.

BIOCHEMICAL

3, 1973

TABLE

1.

ARGIE!ItIE CONTAIIJING

AND

AND

LYSINE

BIOPHYSICAL

CONTEt!T

50 OR MORE AMINO

RESEARCH

OF 83 rLASSES ACID RFSIDIJES.

-----

----_lm-L-.-.---

F’roteins, --..T ryps

--------_I-i nogen

-.-L-&‘ass , Rovi

3 -

Anti

-

trypsin

rhymot

5

plants

Leghemoqlobin

plants

- human

ryps

i nogen

Z-Lactoqlobul

in,

Bovine

AR

!lyoglobin Aloha

Globin, Cy tech

Chain

Hemonlobin Immuno~lohulins, Constant,

Kaopa,

Constant,

Lambda,

Variable

human

Immunoglobulins,

0.9

6.6

II.7

1.1

76.6

1.3

9.5 4.8

1.7

4.6

1.2 I.4

IQ.0

47.2

7

12

1.7

7.6

2

245

4.5

12.5

1.P

5.1

I

I62

3

15

1.0

1.3

152.9

2.?

I?.6

I.?

12.?

141 .I

3.0

11.6

2.1

8.2

136

3

In

7.2

107 145.2

7.4

15.6

2.2

3.3

II.3

2.3

7.4 14.6 7.1

2

106

2.5

7.5

2.4

7.1

2

1

4.9

7 3.7

I.0

18

IQ5 107.8

4.6

6.7 3.4

id

IOQ

4.n

3.2

3.6

2.9

& mouse

human

heavy

mouse & mouse

t

human

Lambda,

15

chains: human

Kappa,

Variable,

123

2

14

lr)

light

229

?

I

Chain

Lys

I 40

40

c “_ Beta

Residues Percent Am ---

of

I

10

ch i ronomus rome

Ave rane

--e--__ tJ0.

1

8

Hemoglobin

PROTEINS

2!GJ%!!~~A~rn~~~~

I

ne

Lactalbumin Ferredoxin

OF

_--_l--l____-

%7. of Proteins

Eukaryotic

COMMUNICATIONS

& mouse

chains:

Constant,

human

1

336

7

27

2.1

8.0

Constant,

rabbit

I

326

I3

19

3.P

Variable,

human

6

5.8

4.2

5.3

5.7 3.8

I

109.7 84

2

4

2.4

4.8

2

204

5

12.5

2.5

h.1

I

84

2

8

2.6

10.1

I

Protease

Inhibitor

-

Lima

Bean

Caseins Haptoglobin Carboni

Alpha c anhydrase,

Hemerythrin, inhibitor,

G lobin.

lamprey

soybean

Glyceraldehyde

3-PO4

Thyrotropin

fluscle

human

worm

T rypsin

Alcohol

Chain

CL and Dehydrogenase triose

PO4

Adrenodoxi

n,

human

bovine i dase

P rophosphol

i pase

, bovine

scorpion

A2,

pi g

a

7

18

2.7

6.9

113

3

II

2.7

9.7

I

7.0

7

71 146

2.R

4.5

I?

3.1

8.9

2

332.5

9.5

27

2.9

8.1

96

3

IO

3.1

IO.4

30

3.2

8

20

3.2

8.0 8. I

3

6

3.3

6.5

3

a

2

5

1

374 248

1

92.

1

118

4

5

307

11

15

3.4 3.6

4.2

1 1

130

5

9

3.8

6.Y

2.5

5.5

3.9

8.7

1

isomerase

gonadotropin,

Carboxypept

hormone

horse

Chorionic

Neurotoxin,

Dehydrogenase

luteinizing

240

I

2

711

63.5

I2

4.9

Vol. 53, No. 3, 1973

Proteins,

BIOCHEMICAL

_I--. Ribonuclease,

Keratin,

B

5

High-sulfur

protein

Trypsin

inhibitor,pancreatic

Trypsin

inhibitor,

Bee

3

pancreatic

rome

venom

Proinsul

h 2 2 ascaris

phosphol

1

ipase

A

1

3

in

Elastase,

porcine

Lipotropin

1

B and

y

2

Prolactin

nerve

growth

G lutamate Parathyroid

5

9.h

4.0

7.7

87.2

3.6

6.6

4.1

153.5

6.5

0

4.2

7.8 0.n

56

2.5

3.5

4.5

h.2.

66

3 6

7

4.5

10.6

10

4.7

7.@

11

2

4.8

2 .4

128

83.6 240

90.5

II 4.5

212

12

10

5.7

4.p

120

7

8

5.8

6.7

1

gon

30

32

6.0

6.4

1

84

5

9

6.0

10.7

61.2

4.2

5.3

6.2

8.4

9

6.3

7.0’

20

6.4

16.0

10.5

6.4

5.6

4

6.6

5.3

8

Histone

II

1

125

8

2

189.5

1

76

5

1

82

R chorionic

protein

Thyrotropin

f3 and -

Lysozyme Trypsin

luteinizing

hormone

6

basic,

Membrane

Trypsin

Inhibitor

Histone

I I I,

Histone

IV

Encephalitogenic calf

11

4

7.9

2.9

116.5

IO

6.5

8.4

5.6

5

129

11.6

6.2

9.n

4.w

1

protein

Maize

1

thymus

1 2

5% 170

65 135 102 9,656

TOTALS

__-Proteins,

*

139

1

bovine

12

2

human

vertebrates

inhibitor,

Myelin

A

gonadotropin,

4.5

11

128

ahloid

5.0

1

1

Hormone

1.2 11.0

1

chicken

Monkey

5.0

5.6

Avidin,

Growth

2 10 9

Hormone venom

LYS

IO.5

factor

ns , snake

Tit-n

194

Dehydrogenase

Neurotoxi

125

Lys

2

Papain Mouse

RESEARCH COMMUNICATIONS

No. of Ave raqe Proteins No. of In Class ~~~.~---~---------L.-_-_. Res i dues At-q

Eukaryotic

Cy tech

AND BIOPHYSICAL

6

4

In.?

6.9

18.5

12.5

10.9

7.4

8

1

12.3

1.5 ’

18

13

13.3

9.6

14.5

IO.5

13.7

IO.84

402.7

668.7

4.17

6.92

-_-_--------

Prokaryotic ------I_-

Rub redoxi

n

Cy t och rome Cy tech

rome

Cytoch

rome

50s

2 1

c2

3 c551 c3

Rihosomal

protein

Neocarzinostatin

A2,

5.

coli

Streptomyces

Thioredoxin Ribonuclease

T,

712

52.5 112

82

0

3

0.0

5.7’

n

17

0.0

15.2

0.3

1n.2

1

103

0.5

0.3

18.5

8.3

n.6

18.5 ’

1

12D

1

12

0.8

10.0

1

109

1

0

0.9

o.n*

1

108

1

10

0.9

9.3

1

in4

1

1

1.n

1.0

Vol. 53, No. 3,1973

light

chain,

tripling

and

of

mutations are

the

"it

specificity

minants" thus

accounting 1969).

greater

abundance

direction

of

higher

and

a difference

arginine

codons and

higher

in

arginine

of

randomly-occurring

rejected

by

between

the

the

-

clostridial

C regions.

S and

to

5

54.8

77

Penicillinase Ferredoxin, Thermolysin, Nuclease,

yellow

Staph.

mosaic

--aureus

Chromatium --Bacillus

thermoproteolyticus

staphylococcal

Cytochrome

B562

Tryptophan

Synthetase

Aspartate

A

transcarbamylase

Penicillinase, Coat

Protein

Alpha

lytic

Lysozym,

1

turnip

E.

licheniformir

- Tobacco protease,

R Chain

Mosaic

Vi rus

myxobact.

virus

1

I88

1

257

TOTALS

C

that

by there

is

-

At-4

Lys

n.?

0.8

-

Residues Percent At-? LyS

1.0

1.3

3 1.2

10

1.1

12.8

1.2

3.6 P.?

1

4

1.3

5.2

7 43

1.6

3 4

1.6

3.7 16.7

1

81

2

2

2.5

1

316

IO

11

3.2

3.5

1

I 4sr

3.4

15.4

1

23 16

2.5

110

5 4

3.6

14.5

1

267

11

13

4.1

4.9

1

152

8

10

5.3

6.6

1

265

24 1.6

5.7

9.0

6.1

1.3

5 1 2

bacteriophage

the

Average No. of Residues -I-

125.8

-

the

accepted

1 shows

274.5

protein

composition

than

mutations,

4 protein

the

whose

lysine

Azurin carrier

in

the

considerations,

2

Coat

a protein,

one

above

Table

C sequences,"

evolve

of

Subtilisin

Acyl

of

C regions.

No. of Proteins In Class

type

deleterious,

from

in

deter-

usually

it

lower point

available

antigenic

removed

the

and

a large

than

point

changes,

constancy

lead

From

most

immunoglobulins

are

the

lysine

a

evolutionary

regions

should

that

various

are

lower

of

have

with

S and

reasons.

----Ferredoxin

(C) of

Prokaryotic

Proteins,

cope

representing

1969

as to

constraints

functional be

to

variability

long, in

incorporated

constant

arginine

a result

S regions

such

of

should

the

functional

by

as

in

RESEARCH COMMUNICATIONS

regions

advantageous

the

If

constrained

regions

rapidly

antibodies

for

(Jukes,

S regions

are

"those

as

(S)(variable)

different

while

times

I suggested

inunologically

of

three

protein.

and is

AND BIOPHYSICAL

about

ancestral

advantageous,

assortment

the

a C region

the in

because

is

BIOCHEMICAL

157.4 198 160.5 3,630

15 9.6

2

6.1

1.0

12.5

12.5

7.9

7.9

106.3

262.5

2.93

7.23

12

Vol. 53, No. 3,1973

BIOCHEMICAL

The prokaryotic than

those

in Table

of the eukaryotes.

in contrast excretory

proteins

to prokaryotes, products

are somewhat

"less

1 average

Perhaps

this

can dispose

such as urea intolerant"

AND BIOPHYSICAL

is

of arginine

even

lower

because

of arginine

and creatinine,

RESEARCH COMMUNICATIONS

many eukaryotes,

by converting and therefore

than

in arginine

are

it

to

eukaryotes

the prokaryotes.

ACKNOWLEDGMENT Support by NASA grant Berkeley, is acknowledged.

NGR 05-003-460

to the

University

of California,

REFERENCES ;T;;lonr,LL.

and Jukes, T. H. (1962) Pharmacol. Reviews, 14:91. E. ( 1966) Delaney, R., Fellows, R. E., Jr. and Lebovitz,?r. Fro;. t&l. Acad. Sci. USA, 56:1762. Jukes, T.-(1969)calGenetics, H. 3:109. King, J. L. and Jukes, (1969)M, T. H. 164:788. Subak-Sharpe, H., Burk, R. R., Crawford, L. V.,xrrison, J. M., Hay , J. and Keir, H. M. (1966) Cold Spr.Harb..$mp;.Quant Biol., -31:737.

714