Short Communication
Open Access
Degeneracy of the Genetic Code has Played an Important
Role in Evolution of Organisms
Kenji Ikehara*
G&L Kyosei Institute, Hikaridai 1-7, Seika-cho, Kyoto 619-0237, Japan
International Institute for Advanced Studies, Kizugawadai 9-3, Kizugawa, Kyoto 619-0225, Japan
International Institute for Advanced Studies, Kizugawadai 9-3, Kizugawa, Kyoto 619-0225, Japan
*Corresponding author: Kenji Ikehara, G&L Kyosei Institute, Hikaridai 1-7, Seika-cho, Kyoto 619-0237, Japan; Fellow, International Institute for Advanced Studies, Kizugawadai 9-3, Kizugawa, Kyoto 619-0225, Japan; Emeritus professor, Nara Women’s University, Kita-uoya-higashi-machi, Nara
630-8506, Japan, Tel: +81-774-73-4478; Fax: +81-774-73-4478; E-mail: ikehara@cc.nara-wu.ac.jp
Received: May 28, 2016; Accepted: July 15, 2016; Published: July 25, 2016
Citation: Ikehara K (2016) Degeneracy of the Genetic Code has Played an Important Role in Evolution of Organisms. SOJ Genet Sci 3(1):1-3. DOI: 10.15226/2377-4274/3/1/00111
Abstract
The genetic code is degenerate mainly at the third codon position.
However, the reason of the degeneracy still remains unknown. On the
other hand, we have proposed GC-NSF(a) hypothesis, assuming that
entirely new gene has emerged from non-stop frame on antisense
codon sequence of GC-rich gene (GC-NSF(a)). Amino acid sequence of
a protein encoded by GC-NSF(a) widely varies without any change of
amino acid sequence of a protein produced from the corresponding
gene on sense strand. Therefore, various protein sequences with
an amino acid sequence can be repeatedly examined, if a required
function is found on a surface of the protein from the GC-NSF(a).
This indicates that the degeneracy of the genetic code has largely
contributed to produce entirely new protein from GC-NSF(a). Thus,
entirely new proteins having a required function could be produced
effectively. The degeneracy of the genetic code made it possible
for organisms to prosper on Earth. Organisms, which did not use a
degenerate genetic code, would extinguish from this planet. This is
one significant point of the genetic code.
Keywords: Protein 0th-order Structure; Degeneracy of the Genetic Code; Origin of Entirely New Gene
Keywords: Protein 0th-order Structure; Degeneracy of the Genetic Code; Origin of Entirely New Gene
Introduction
Genetic information transferred from DNA to mRNA by
transcription is transmitted to protein through translation on
ribosome. During the translation, the universal or standard
genetic code written with triplet base sequence is used, which
specifies a kind of amino acid, like as that GUC, CAC, AAG and UUC
correspond to Val, His, Lys and Phe, respectively. As well known,
the genetic code is degenerate mainly at the third codon position,
for example GGN, GCN and GUN, 4 codons each, code for Gly, Ala
and Val, respectively (Figure 1). However, it is totally unknown
about the reason why the genetic code is degenerate.
The genetic code occupies a core position connecting genetic function with catalytic function in the fundamental life system (Figure 2). This means that the genetic code is not only a simple representation of triplet base sequence with an amino acid, but also a key element when one wants to make clear formation process of the fundamental life system, which is composed of gene (genetic function), genetic code and protein (catalytic function), leading to solving the riddle of the origin of life.
In this Short Communication, I describe that the degeneracy of the genetic code plays an important role in producing entirely new (EntNew) gene and the corresponding EntNew protein from nonstop frame on anti-sense strand of GC-rich gene (GC-NSF(a)), according to the GC-NSF(a) hypothesis, which I have proposed [1-3] (Figure 3). That would be the significance of the genetic code.
The genetic code occupies a core position connecting genetic function with catalytic function in the fundamental life system (Figure 2). This means that the genetic code is not only a simple representation of triplet base sequence with an amino acid, but also a key element when one wants to make clear formation process of the fundamental life system, which is composed of gene (genetic function), genetic code and protein (catalytic function), leading to solving the riddle of the origin of life.
In this Short Communication, I describe that the degeneracy of the genetic code plays an important role in producing entirely new (EntNew) gene and the corresponding EntNew protein from nonstop frame on anti-sense strand of GC-rich gene (GC-NSF(a)), according to the GC-NSF(a) hypothesis, which I have proposed [1-3] (Figure 3). That would be the significance of the genetic code.
Figure 1 :Degeneracy of the genetic code. Almost all extant organisms
on the Earth are using so called universal or standard genetic code,
which degenerates mainly at the third codon position of the code.
Figure 2 :Position of genetic code in fundamental life system. Genetic
code occupies a core position connecting genetic function composed of
DNA and mRNA with catalytic function carried out protein and metabolism
in the life system.
Theories proposed for new gene formation
Organisms on the Earth have evolved gradually and steadily,
and sometimes abruptly, over several billion years. The evolution
of lives should have tightly coupled to acquisition of new function
required to adapt to new environment.
Two main routes for creation of new genes have been proposed so far. One is gene duplication theory proposed by Ohno [4], predicting that after duplication of a gene, one duplicate may acquire a new adaptive function, while the other duplicate retains the original function. The second is exon-shuffling theory proposed by Gilbert, et al. [5], assuming that new functional gene is created as a new combination of exons shuffled among two or more genes.
However, both of the theories do not explain the most fundamental problem on the creation of EntNew gene or the first ancestor gene in a family, from which various descendant genes could be derived. This means that the most important and key problem about formation of a gene family remains unsolved.
On the contrary, I have proposed GC-NSF(a) hypothesis on creation of EntNew gene [1-3]. The hypothesis assumes that EntNew gene, which is totally different from any previously existing gene, is created from GC-NSF(a) after gene duplication (Figure 3). I would like to emphasize here that GC-NSF(a) hypothesis is not a purely theoretical idea but one attained by database analysis of microbial genes and proteins, which have been obtained by experiments.
Two main routes for creation of new genes have been proposed so far. One is gene duplication theory proposed by Ohno [4], predicting that after duplication of a gene, one duplicate may acquire a new adaptive function, while the other duplicate retains the original function. The second is exon-shuffling theory proposed by Gilbert, et al. [5], assuming that new functional gene is created as a new combination of exons shuffled among two or more genes.
However, both of the theories do not explain the most fundamental problem on the creation of EntNew gene or the first ancestor gene in a family, from which various descendant genes could be derived. This means that the most important and key problem about formation of a gene family remains unsolved.
On the contrary, I have proposed GC-NSF(a) hypothesis on creation of EntNew gene [1-3]. The hypothesis assumes that EntNew gene, which is totally different from any previously existing gene, is created from GC-NSF(a) after gene duplication (Figure 3). I would like to emphasize here that GC-NSF(a) hypothesis is not a purely theoretical idea but one attained by database analysis of microbial genes and proteins, which have been obtained by experiments.
The reason why EntNew gene can be produced from
GC-NSF(a)
The reason why EntNew genes can be produced according to
the GC-NSF(a) hypothesis is as follows.
1. Protein encoded by GC-NSF(a) satisfies the six conditions for formation of water-soluble globular protein, which were obtained as average ranges (average value +/- standard deviation) of six properties (hydropathy, α-helix, β-sheet and turn/coil formabilities, and acidic amino acid and basic amino acid compositions) of water-soluble
1. Protein encoded by GC-NSF(a) satisfies the six conditions for formation of water-soluble globular protein, which were obtained as average ranges (average value +/- standard deviation) of six properties (hydropathy, α-helix, β-sheet and turn/coil formabilities, and acidic amino acid and basic amino acid compositions) of water-soluble
Figure 3 :GC-NSF(a) hypothesis. The hypothesis assumes that entirely
new gene is created from GC-NSF(a) after gene duplication. Thick line
and broken line indicate a gene on sense strand and non-stop frame on
antisense strand, respectively.
globular proteins encoded by genomes of seven extant
microorganisms carrying chromosomal DNA with widely
different GC content [6]. This indicates that a polypeptide
chain produced from GC-NSF(a) would be folded into
water-soluble globular structure at a high probability.
2. The reason why protein encoded by GC-NSF(a) well satisfies the six conditions is partly because GC-NSF(a) is similar to SNS repeating codon sequence or (SNS)n, which also satisfies the six conditions [7]. S and N mean G or C and any one of four bases.
3. GC-NSF(a) codes for a protein, which has completely different amino acid sequence from any previously existing protein but has a similar amino acid composition to those of proteins encoded by GC-rich genome (Figure 4). The protein encoded by GC-NSF(a) has a nearly random amino acid sequence in protein 0th-order structure. Protein 0th-order structure is a specific amino acid composition, in which even random joining of amino acids produces water-soluble globular protein at a high probability. One of such kind of protein 0th-order structures is GC-NSF(a)-encoding amino acid composition similar to SNS-encoding amino acid composition (Figure 4). Other protein 0th-order structures are SNS-encoding ten amino acids ([GADV]-amino acids plus Glu[E], Leu[L], Pro[P], His [H], Gln [Q] and Arg [R]) and GNC-encoding four [GADV]-amino acids. [GADV] means four amino acids; Gly[G], Ala[A], Asp[D] and Val[V].
4. As well known, sequence diversity of even a small protein composed of 100 amino acids is extraordinary large, as reaching to about 20100 = ~10130. The tremendously large diversity makes it possible to produce protein without any homology with previously existing proteins or an EntNew protein from a GC-NSF(a), because the probability which an amino acid sequence of a protein arisen from a GC-NSF(a) coincides with any one of previously existing proteins is just about nil, as ~1/10130. Of course, sequence diversity of a protein encoded by GC-NSF(a) is much smaller than ~10130, since amino acid composition of the protein is extremely deviate from that of a protein containing about equal amount of 20 amino acids. However, the diversity is larger than ~10100, the still extraordinary large diversity value of a protein encoded by (SNS)100, similar to codon sequence of GCNSF( a) (Figure 4). Note that SNS codes for 10 amino acids.
5. In addition, the degeneracy at the third codon position increases the probability that EntNew protein is produced from GC-NSF(a), because the EntNew protein could be generated without any change of amino acid sequence encoded by a GC-rich gene on sense strand. The base replacement at the third codon position of GCrich gene corresponds to the first codon position of GCNSF( a) (Figure 5). If a required function were detected on a surface of the protein encoded by one of various GCNSF( a)s, the protein could be newly born and successively evolve to mature protein (8).
Therefore, degeneration of the genetic code is quite important for production of EntNew protein; because every amino acid sequence appeared upon base replacement could be examined until a required catalytic activity is found.
2. The reason why protein encoded by GC-NSF(a) well satisfies the six conditions is partly because GC-NSF(a) is similar to SNS repeating codon sequence or (SNS)n, which also satisfies the six conditions [7]. S and N mean G or C and any one of four bases.
3. GC-NSF(a) codes for a protein, which has completely different amino acid sequence from any previously existing protein but has a similar amino acid composition to those of proteins encoded by GC-rich genome (Figure 4). The protein encoded by GC-NSF(a) has a nearly random amino acid sequence in protein 0th-order structure. Protein 0th-order structure is a specific amino acid composition, in which even random joining of amino acids produces water-soluble globular protein at a high probability. One of such kind of protein 0th-order structures is GC-NSF(a)-encoding amino acid composition similar to SNS-encoding amino acid composition (Figure 4). Other protein 0th-order structures are SNS-encoding ten amino acids ([GADV]-amino acids plus Glu[E], Leu[L], Pro[P], His [H], Gln [Q] and Arg [R]) and GNC-encoding four [GADV]-amino acids. [GADV] means four amino acids; Gly[G], Ala[A], Asp[D] and Val[V].
4. As well known, sequence diversity of even a small protein composed of 100 amino acids is extraordinary large, as reaching to about 20100 = ~10130. The tremendously large diversity makes it possible to produce protein without any homology with previously existing proteins or an EntNew protein from a GC-NSF(a), because the probability which an amino acid sequence of a protein arisen from a GC-NSF(a) coincides with any one of previously existing proteins is just about nil, as ~1/10130. Of course, sequence diversity of a protein encoded by GC-NSF(a) is much smaller than ~10130, since amino acid composition of the protein is extremely deviate from that of a protein containing about equal amount of 20 amino acids. However, the diversity is larger than ~10100, the still extraordinary large diversity value of a protein encoded by (SNS)100, similar to codon sequence of GCNSF( a) (Figure 4). Note that SNS codes for 10 amino acids.
5. In addition, the degeneracy at the third codon position increases the probability that EntNew protein is produced from GC-NSF(a), because the EntNew protein could be generated without any change of amino acid sequence encoded by a GC-rich gene on sense strand. The base replacement at the third codon position of GCrich gene corresponds to the first codon position of GCNSF( a) (Figure 5). If a required function were detected on a surface of the protein encoded by one of various GCNSF( a)s, the protein could be newly born and successively evolve to mature protein (8).
Therefore, degeneration of the genetic code is quite important for production of EntNew protein; because every amino acid sequence appeared upon base replacement could be examined until a required catalytic activity is found.
Discussion
Base at the third codon position on a sense strand can be
replaced widely without any change of amino acid sequence,
because of degenerate of the genetic code at the position. On the
other hand, this causes to change amino acid sequence encoded
by GC-NSF(a) at a high probability, since the change of base at the
first codon position induces amino acid replacement of a protein
encoded by GC-NSF(a). Nevertheless, amino acid composition,
not amino acid sequence, of the protein does not largely deviate
from the protein 0th-order structure. The reason is because GC
Figure 4 :Base compositions of GC-NSF(a) at three codon positions.
Base compositions at three codon positions of both GCNSF(
a) and GC-rich gene are similar to each other and can be
approximated to SNS. Base compositions at the three codon positions
were obtained as average
values of seven genes of Pseudomonas
aeruginosa carrying GC-rich genome.
Figure 5 :Possible amino acid sequences encoded by a GC-NSF(a). For
example, 1,536 (4x2x3x2x4x4x2) amino acid sequences can be encoded
by only 7 codons of GC-NSF(a), while amino acid sequence encoded by a
GC-rich gene is retained unchanged due to the degeneracy of the genetic
code at the third codon position, as shown above.
mutation pressure acting on GC-rich gene of a microorganism
carrying GC-rich genome remains to keep the composition nearly
in SNS-encoding amino acid composition, which is also one of the
protein 0th-order structures (Figure 4).
Thus, it is considered that EntNew protein having a required function could be produced effectively owning to the degeneracy of the genetic code, and that organisms on this planet, which have used the degenerate genetic code, have prospered, although it might be as a result. Inversely saying, organisms, which did not use a degenerate genetic code, would extinguish from the Earth, even if the organisms once emerged on this planet. The genetic code of organisms prospering on this planet must be degenerate, for whatever reason for the degeneracy.
Then, from when did the genetic code degenerate? According to my scenario, GNC-SNS primitive genetic code hypothesis [6], on the origin and evolution of the genetic code, it can be supposed that the degeneracy started at the evolutionary step from the first genetic code GNC to the next code GNS, which encodes five amino acids, GNC-encoding [GADV]-amino acids plus Glu [E]. The GNS code might trigger to evolve it to SNS code and to produce effectively EntNew gene/protein from antisense codon sequence ((SNS)n sequence) of (SNS)n gene, as similarly as EntNew Gene/ protein emerged from GC-NSF(a) (Figure 3).
Thus, it is considered that EntNew protein having a required function could be produced effectively owning to the degeneracy of the genetic code, and that organisms on this planet, which have used the degenerate genetic code, have prospered, although it might be as a result. Inversely saying, organisms, which did not use a degenerate genetic code, would extinguish from the Earth, even if the organisms once emerged on this planet. The genetic code of organisms prospering on this planet must be degenerate, for whatever reason for the degeneracy.
Then, from when did the genetic code degenerate? According to my scenario, GNC-SNS primitive genetic code hypothesis [6], on the origin and evolution of the genetic code, it can be supposed that the degeneracy started at the evolutionary step from the first genetic code GNC to the next code GNS, which encodes five amino acids, GNC-encoding [GADV]-amino acids plus Glu [E]. The GNS code might trigger to evolve it to SNS code and to produce effectively EntNew gene/protein from antisense codon sequence ((SNS)n sequence) of (SNS)n gene, as similarly as EntNew Gene/ protein emerged from GC-NSF(a) (Figure 3).
Acknowledgements
I am very grateful to Dr. Tadashi Oishi (G&L Kyosei
Institute, Emeritus professor of Nara Women’s University) for
encouragement throughout my research on GADV hypothesis on
the origin of life.
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