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1.
Ikehara K 《Journal of biosciences》2002,27(2):165-186
We have investigated the origin of genes, the genetic code, proteins and life using six indices (hydropathy, α-helix, β-sheet
and β-turn formabilities, acidic amino acid content and basic amino acid content) necessary for appropriate three-dimensional
structure formation of globular proteins. From the analysis of microbial genes, we have concluded that newly-born genes are
products of nonstop frames (NSF) on antisense strands of microbial GC-rich genes [GC-NSF(a)] and from SNS repeating sequences
[(SNS)n] similar to the GC-NSF(a) (S and N mean G or C and either of four bases, respectively). We have also proposed that the universal
genetic code used by most organisms on the earth presently could be derived from a GNC-SNS primitive genetic code. We have
further presented the [GADV]-protein world hypothesis of the origin of life as well as a hypothesis of protein production,
suggesting that proteins were originally produced by random peptide formation of amino acids restricted in specific amino
acid compositions termed as GNC-, SNS and GC-NSF(a)-0th order structures of proteins. The [GADV]-protein world hypothesis
is primarily derived from the GNC-primitive genetic code hypothesis. It is also expected that basic properties of extant genes
and proteins could be revealed by considerations based on the scenario with four stages
This review is a modified English version of the paper, which was written in Japanese and published inViva Origino 2001 29 66–85. 相似文献
2.
Ramin Amirnovin 《Journal of molecular evolution》1997,44(5):473-476
A computer program was used to test Wong's coevolution theory of the genetic code. The codon correlations between the codons
of biosynthetically related amino acids in the universal genetic code and in randomly generated genetic codes were compared.
It was determined that many codon correlations are also present within random genetic codes and that among the random codes
there are always several which have many more correlations than that found in the universal code. Although the number of correlations
depends on the choice of biosynthetically related amino acids, the probability of choosing a random genetic code with the
same or greater number of codon correlations as the universal genetic code was found to vary from 0.1% to 34% (with respect
to a fairly complete listing of related amino acids). Thus, Wong's theory that the genetic code arose by coevolution with
the biosynthetic pathways of amino acids, based on codon correlations between biosynthetically related amino acids, is statistical
in nature.
Received: 8 August 1996 / Accepted: 26 December 1996 相似文献
3.
How did the ``universal' genetic code arise? Several hypotheses have been put forward, and the code has been analyzed extensively
by authors looking for clues to selection pressures that might have acted during its evolution. But this approach has been
ineffective. Although an impressive number of properties has been attributed to the universal code, it has been impossible
to determine whether selection on any of these properties was important in the code's evolution or whether the observed properties
arose as a consequence of selection on some other characteristic. Therefore we turned the question around and asked, what
would a genetic code look like if it had evolved in response to various different selection pressures? To address this question,
we constructed a genetic algorithm. We found first that selecting on a particular measure yields codes that are similar to
each other. Second, we found that the universal code is far from minimized with respect to the effects of mutations (or translation
errors) on the amino acid compositions of proteins. Finally, we found that the codes that most closely resembled real codes
were those generated by selecting on aspects of the code's structure, not those generated by selecting to minimize the effects
of amino acid substitutions on proteins. This suggests that the universal genetic code has been selected for a particular
structure—a structure that confers an important flexibility on the evolution of genes and proteins—and that the particular
assignments of amino acids to codons are secondary.
Received: 29 December 1998 / Accepted: 8 July 1999 相似文献
4.
Jeffrey Tze-Fei Wong 《Origins of life and evolution of the biosphere》2007,37(4-5):403-408
The coevolution theory proposes that primordial proteins consisted only of those amino acids readily obtainable from the prebiotic
environment, representing about half the twenty encoded amino acids of today, and the missing amino acids entered the system
as the code expanded along with pathways of amino acid biosynthesis. The isolation of genetic code mutants, and the antiquity
of pretran synthesis revealed by the comparative genomics of tRNAs and aminoacyl-tRNA synthetases, have combined to provide
a rigorous proof of the four fundamental tenets of the theory, thus solving the riddle of the structure of the universal genetic
code.
Presented at: International School of Complexity – 4th Course: Basic Questions on the Origins of Life; “Ettore Majorana” Foundation and Centre for Scientific Culture, Erice, Italy, 1–6 October 2006. 相似文献
5.
A paper (Amirnovin R, J Mol Evol 44:473–476, 1997) seems to undermine the validity of the coevolution theory of genetic code
origin by shedding doubt on the connection between the biosynthetic relationships between amino acids and the organization
of the genetic code, at a time when the literature on the topic takes this for granted. However, as a few papers cite this
paper as evidence against the coevolution theory, and to cast aside all doubt on the subject, we have decided to reanalyze
the statistical bases on which this theory is founded. We come to the following conclusions: (1) the methods used in the above
referred paper contain certain mistakes, and (2) the statistical foundations on which the coevolution theory is based are
extremely robust. We have done this by critically appraising Amirnovin's paper and suggesting an alternative method based
on the generation of random codes which, along with the method reported in the literature, allows us to evaluate the significance,
in the genetic code, of different sets of amino acid pairs in biosynthetic relationships. In particular, by using this method
and after building up a certain set of amino acid pairs reflecting the expectations of the coevolution theory, we show that
the presence of this set in the genetic code would be obtained, purely by chance, with a probability of 6 × 10−5. This observation seems to provide particularly strong support to the coevolution theory.
Received: 28 June 1999 / Accepted: 23 October 1999 相似文献
6.
We simulate a deterministic population genetic model for the coevolution of genetic codes and protein-coding genes. We use
very simple assumptions about translation, mutation, and protein fitness to calculate mutation-selection equilibria of codon
frequencies and fitness in a large asexual population with a given genetic code. We then compute the fitnesses of altered
genetic codes that compete to invade the population by translating its genes with higher fitness. Codes and genes coevolve
in a succession of stages, alternating between genetic equilibration and code invasion, from an initial wholly ambiguous coding
state to a diversified frozen coding state. Our simulations almost always resulted in partially redundant frozen genetic codes.
Also, the range of simulated physicochemical properties among encoded amino acids in frozen codes was always less than maximal.
These results did not require the assumption of historical constraints on the number and type of amino acids available to
codes nor on the complexity of proteins, stereochemical constraints on the translational apparatus, nor mechanistic constraints
on genetic code change. Both the extent and timing of amino-acid diversification in genetic codes were strongly affected by
the message mutation rate and strength of missense selection. Our results suggest that various omnipresent phenomena that
distribute codons over sites with different selective requirements—such as the persistence of nonsynonymous mutations at equilibrium,
the positive selection of the same codon in different types of sites, and translational ambiguity—predispose the evolution
of redundancy and of reduced amino acid diversity in genetic codes.
Received: 21 December 2000 / Accepted: 12 March 2001 相似文献
7.
We consider a model of the origin of genetic code organization incorporating the biosynthetic relationships between amino acids and their physicochemical properties. We study the behavior of the genetic code in the set of codes subject both to biosynthetic constraints and to the constraint that the biosynthetic classes of amino acids must occupy only their own codon domain, as observed in the genetic code. Therefore, this set contains the smallest number of elements ever analyzed in similar studies. Under these conditions and if, as predicted by physicochemical postulates, the amino acid properties played a fundamental role in genetic code organization, it can be expected that the code must display an extremely high level of optimization. This prediction is not supported by our analysis, which indicates, for instance, a minimization percentage of only 80%. These observations can therefore be more easily explained by the coevolution theory of genetic code origin, which postulates a role that is important but not fundamental for the amino acid properties in the structuring of the code. We have also investigated the shape of the optimization landscape that might have arisen during genetic code origin. Here, too, the results seem to favor the coevolution theory because, for instance, the fact that only a few amino acid exchanges would have been sufficient to transform the genetic code (which is not a local minimum) into a much better optimized code, and that such exchanges did not actually take place, seems to suggest that, for instance, the reduction of translation errors was not the main adaptive theme structuring the genetic code. 相似文献
8.
Two forces are in general, hypothesized to have influenced the origin of the organization of the genetic code: the physicochemical
properties of amino acids and their biosynthetic relationships. In view of this, we have considered a model incorporating
these two forces. In particular, we have studied the optimization level of the physicochemical properties of amino acids in
the set of amino acid permutation codes that respects the biosynthetic relationships between amino acids. Where the properties
of amino acids are represented by polarity and molecular volume we obtain indetermination percentages in the organization
of the genetic code of approximately 40%. This indicates that the contingent factor played a significant role in structuring
the genetic code. Furthermore, this result is in agreement with the genetic code coevolution hypothesis, which attributes
a merely ancillary role to the properties of amino acids while it suggests that it was their biosynthetic relationships that
organized the code. Furthermore, this result does not favor the stereochemical models proposed to explain the origin of the
genetic code. On the other hand, where the properties of amino acids are represented by polarity alone, we obtain an indetermination
percentage of at least 21.5%. This might suggest that the polarity distances played an important role and would therefore
provide evidence in favor of the physicochemical hypothesis of genetic code origin. Although, overall, the analysis might
have given stronger support to the latter hypothesis, this did not actually occur. The results are therefore discussed in
the context of the different theories proposed to explain the origin of the genetic code.
Received: 10 September 1996 / Accepted: 3 March 1997 相似文献
9.
We have assumed that the coevolution theory of genetic code origin (Wong JT, Proc Natl Acad Sci USA 72:1909–1912, 1975) is
essentially correct. This theory makes it possible to identify at least 10 evolutionary stages through which genetic code
organization might have passed prior to reaching its current form. The calculation of the minimization level of all these
evolutionary stages leads to the following conclusions. (1) The minimization percentages increased linearly with the number
of amino acids codified in the codes of the various evolutionary stages when only the sense changes are considered in the
analysis. This seems to favor the physicochemical theory of genetic code origin even if, as discussed in the paper, this observation
is also compatible with the coevolution theory. (2) For the first seven evolutionary stages of the genetic code, this trend
is less clear and indeed is inverted when we consider the global optimisation of the codes due to both sense changes and synonymous
changes. This inverse correlation between minimization percentages and the number of amino acids codified in the codes of
the intermediate stages seems to favor neither the physicochemical nor the stereochemical theories of genetic code origin,
as it is in the early and intermediate stages of code development that these theories would expect minimization to have played
a crucial role, and this does not seem to be the case. However, these results are in agreement with the coevolution theory,
which attributes a role to the physicochemical properties of amino acids that, while important, is nevertheless subordinate
to the mechanism which concedes codons from the precursor amino acids to the product amino acids as the primary factor determining
the evolutionary structuring of the genetic code. The results are therefore discussed in the context of the various theories
proposed to explain genetic code origin.
Received: 25 October 1998 / Accepted: 19 February 1999 相似文献
10.
Massimo Di Giulio 《Journal of molecular evolution》2001,53(6):724-732
Ronneberg et al. (Proc Natl Acad Sci USA 97:13690–13695, 2000) recently suggested abandoning the coevolution theory of genetic
code origin on the basis of two pieces of evidence. They (1) criticize the use of several pairs of amino acids in a precursor–product
relationship to support this theory and (2) suggest a new set of codes in which to investigate the statistical bases of the
coevolution theory, reaching the conclusion that this theory is not statistically validated in this set. In this paper I critically
analyze the robustness of these conclusions. Observations and arguments lead to the belief that the pairs of amino acids in
a precursor–product relationship originally used by the coevolution theory are such, or may at least be interpreted as such,
and are therefore a manifestation of this theory. Furthermore, the new set of codes that Ronneberg et al. suggest is open
to criticism and is thus substituted by the set of amino acid permutation codes, in which even the pairs of amino acids they
favor end up by supporting the coevolution theory. Overall, the analysis seems to show that the paper by Ronneberg et al.
is of minor scientific value while the coevolution theory seems to be one of the best theories at our disposal for explaining
the evolutionary organisation of the genetic code and is, contrary to their claims, statistically well validated.
Received: 21 February 2001 / Accepted: 22 May 2001 相似文献
11.
We isolated RNAs by selection–amplification, selecting for affinity to Phe–Sepharose and elution with free l-phenylalanine. Constant sequences did not contain Phe condons or anticodons, to avoid any possible confounding influence
on initially randomized sequences. We examined the eight most frequent Phe-binding RNAs for inclusion of coding triplets.
Binding sites were defined by nucleotide conservation, protection, and interference data. Together these RNAs comprise 70%
of the 105 sequenced RNAs. The K
D for the strongest sites is ≈50 μM free amino acid, with strong stereoselectivity. One site strongly distinguishes free Phe from Trp and Tyr, a specificity
not observed previously. In these eight Phe-binding RNAs, Phe codons are not significantly associated with Phe binding sites.
However, among 21 characterized RNAs binding Phe, Tyr, Arg, and Ile, containing 1342 total nucleotides, codons are 2.7-fold
more frequent within binding sites than in surrounding sequences in the same molecules. If triplets were not specifically related to binding sites, the probability of this distribution would be 4.8 × 10−11. Therefore, triplet concentration within amino acid binding sites taken together is highly likely. In binding sites for Arg,
Tyr, and Ile cognate codons are overrepresented. Thus Arg, Tyr, and Ile may be amino acids whose codons were assigned during
an era of direct RNA–amino acid affinity. In contrast, Phe codons arguably were assigned by another criterion, perhaps during
later code evolution. 相似文献
12.
We studied 10 protein-coding mitochondrial genes from 19 mammalian species to evaluate the effects of 10 amino acid properties
on the evolution of the genetic code, the amino acid composition of proteins, and the pattern of nonsynonymous substitutions.
The 10 amino acid properties studied are the chemical composition of the side chain, two polarity measures, hydropathy, isoelectric
point, volume, aromaticity, aliphaticity, hydrogenation, and hydroxythiolation. The genetic code appears to have evolved toward
minimizing polarity and hydropathy but not the other seven properties. This can be explained by our finding that the presumably
primitive amino acids differed much only in polarity and hydropathy, but little in the other properties. Only the chemical
composition (C) and isoelectric point (IE) appear to have affected the amino acid composition of the proteins studied, that
is, these proteins tend to have more amino acids with typical C and IE values, so that nonsynonymous mutations tend to result
in small differences in C and IE. All properties, except for hydroxythiolation, affect the rate of nonsynonymous substitution,
with the observed amino acid changes having only small differences in these properties, relative to the spectrum of all possible
nonsynonymous mutations.
Received: 2 January 1998 / Accepted: 25 April 1998 相似文献
13.
A new method for looking at relationships between nucleotide sequences has been used to analyze divergence both within and
between the families of isoaccepting tRNA sets. A dendrogram of the relationships between 21 tRNA sets with different amino
acid specificities is presented as the result of the analysis. Methionine initiator tRNAs are included as a separate set.
The dendrogram has been interpreted with respect to the final stage of the evolutionary pathway with the development of highly
specific tRNAs from ambiguous molecular adaptors. The location of the sets on the dendrogram was therefore analyzed in relation
to hypotheses on the origin of the genetic code: the coevolution theory, the physicochemical hypothesis, and the hypothesis
of ambiguity reduction of the genetic code. Pairs of 16 sets of isoacceptor tRNAs, whose amino acids are in biosynthetic relationships,
occupied contiguous positions on the dendrogram, thus supporting the coevolution theory of the genetic code.
Received: 4 May 1998 / Accepted: 11 July 1998 相似文献
14.
Thomas Cavalier-Smith 《Journal of molecular evolution》2001,53(4-5):555-595
I attempt to sketch a unified picture of the origin of living organisms in their genetic, bioenergetic, and structural aspects.
Only selection at a higher level than for individual selfish genes could power the cooperative macromolecular coevolution
required for evolving the genetic code. The protein synthesis machinery is too complex to have evolved before membranes. Therefore
a symbiosis of membranes, replicators, and catalysts probably mediated the origin of the code and the transition from a nucleic
acid world of independent molecular replicators to a nucleic acid/protein/lipid world of reproducing organisms. Membranes
initially functioned as supramolecular structures to which different replicators attached and were selected as a higher-level
reproductive unit: the proto-organism. I discuss the roles of stereochemistry, gene divergence, codon capture, and selection
in the code's origin. I argue that proteins were primarily structural not enzymatic and that the first biological membranes
consisted of amphipathic peptidyl-tRNAs and prebiotic mixed lipids. The peptidyl-tRNAs functioned as genetically-specified
lipid analogues with hydrophobic tails (ancestral signal peptides) and hydrophilic polynucleotide heads. Protoribosomes arose
from two cooperating RNAs: peptidyl transferase (large subunit) and mRNA-binder (small subunit). Early proteins had a second
key role: coupling energy flow to the phosphorylation of gene and peptide precursors, probably by lithophosphorylation by
membrane-anchored kinases scavenging geothermal polyphosphate stocks. These key evolutionary steps probably occurred on the
outer surface of an `inside out-cell' or obcell, which evolved an unambiguous hydrophobic code with four prebiotic amino acids
and proline, and initiation by isoleucine anticodon CAU; early proteins and nucleozymes were all membrane-attached. To improve
replication, translation, and lithophosphorylation, hydrophilic substrate-binding and catalytic domains were later added to
signal peptides, yielding a ten-acid doublet code. A primitive proto-ecology of molecular scavenging, parasitism, and predation
evolved among obcells. I propose a new theory for the origin of the first cell: fusion of two cup-shaped obcells, or hemicells,
to make a protocell with double envelope, internal genome and ribosomes, protocytosol, and periplasm. Only then did water-soluble
enzymes, amino acid biosynthesis, and intermediary metabolism evolve in a concentrated autocatalytic internal cytosolic soup,
causing 12 new amino acid assignments, termination, and rapid freezing of the 22-acid code. Anticodons were recruited sequentially:
GNN, CNN, INN, and *UNN. CO2 fixation, photoreduction, and lipid synthesis probably evolved in the protocell before photophosphorylation. Signal recognition
particles, chaperones, compartmented proteases, and peptidoglycan arose prior to the last common ancestor of life, a complex
autotrophic, anaerobic green bacterium.
Received: 19 February 2001 / Accepted: 9 April 2001 相似文献
15.
Edward N. Trifonov Alla Kirzhner Valery M. Kirzhner Igor N. Berezovsky 《Journal of molecular evolution》2001,53(4-5):394-401
Evolution of proteins encoded in nucleotide sequences began with the advent of the triplet code. The chronological order
of the appearance of amino acids on the evolution scene and the steps in the evolution of the triplet code have been recently
reconstructed (Trifonov, 2000b) on the basis of 40 different ranking criteria and hypotheses. According to the consensus chronology,
the pair of complementary GGC and GCC codons for the amino acids alanine and glycine appeared first. Other codons appeared
as complementary pairs as well, which divided their respective amino acids into two alphabets, encoded by triplets with either
central purines or central pyrimidines: G, D, S, E, N, R, K, Q, C, H, Y, and W (Glycine alphabet G) and A, V, P, S, L, T, I, F, and M (Alanine alphabet A). It is speculated that the earliest polypeptide chains were very short, presumably of uniform length, belonging to two alphabet
types encoded in the two complementary strands of the earliest mRNA duplexes. After the fusion of the minigenes, a mosaic
of the alphabets would form. Traces of the predicted mosaic structure have been, indeed, detected in the protein sequences
of complete prokaryotic genomes in the form of weak oscillations with the period 12 residues in the form of alteration of
two types of 6 residue long units. The next stage of protein evolution corresponded to the closure of the chains in the loops
of the size 25–30 residues (Berezovsky et al., 2000). Autocorrelation analysis of proteins of 23 complete archaebacterial
and eubacterial genomes revealed that the preferred distances between valine, alanine, glycine, leucine, and isoleucine along
the sequences are in the same range of 25–30 residues, indicating that the loops are primarily closed by hydrophobic interactions
between the ends of the loops. The loop closure stage is followed by the formation of typical folds of 100–200 amino acids,
via end-to-end fusion of the genes encoding the loop-size chains. This size was apparently dictated by the optimal ring closure
for DNA. In both cases the closure into the ring (loop) rendered evolutionarily advantageous stability to the respective structures.
Further gene fusions lead to the formation of modern multidomain proteins. Recombinational gene splicing is likely to have
appeared after the DNA circularization stage.
Received: 21 December 2000 / Accepted: 28 February 2001 相似文献
16.
To explore how chemical structures of both nucleobases and amino acids may have played a role in shaping the genetic code,
numbers of sp2 hybrid nitrogen atoms in nucleobases were taken as a determinative measure for empirical stereo-electronic property to analyze
the genetic code. Results revealed that amino acid hydropathy correlates strongly with the sp2 nitrogen atom numbers in nucleobases rather than with the overall electronic property such as redox potentials of the bases,
reflecting that stereo-electronic property of bases may play a role. In the rearranged code, five simple but stereo-structurally
distinctive amino acids (Gly, Pro, Val, Thr and Ala) and their codon quartets form a crossed intersection “core”. Secondly,
a re-categorization of the amino acids according to their β-carbon stereochemistry, verified by charge density (at β-carbon)
calculation, results in five groups of stereo-structurally distinctive amino acids, the group leaders of which are Gly, Pro,
Val, Thr and Ala, remarkably overlapping the above “core”. These two lines of independent observations provide empirical arguments
for a contention that a seemingly “frozen” “core” could have formed at a certain evolutionary stage. The possible existence
of this codon “core” is in conformity with a previous evolutionary model whereby stereochemical interactions may have shaped
the code. Moreover, the genetic code listed in UCGA succession together with this codon “core” has recently facilitated an
identification of the unprecedented icosikaioctagon symmetry and bi-pyramidal nature of the genetic code. 相似文献
17.
Song-Kun Shyue Stéphane Boissinot Horacio Schneider Iracilda Sampaio Maria Paula Schneider C.R. Abee Lawrence Williams David Hewett-Emmett Harry G. Sperling Jill A. Cowing Kanwaljit S. Dulai David M. Hunt Wen-Hsiung Li 《Journal of molecular evolution》1998,46(6):697-702
Although most New World monkeys have only one X-linked photopigment locus, many species have three polymorphic alleles at
the locus. The three alleles in the squirrel monkey and capuchin have spectral peaks near 562, 550, and 535 nm, respectively,
and the three alleles in the marmoset and tamarin have spectral peaks near 562, 556, and 543 nm, respectively. To determine
the amino acids responsible for the spectral sensitivity differences among these pigment variants, we sequenced all exons
of the three alleles in each of these four species. From the deduced amino acid sequences and the spectral peak information
and from previous studies of the spectral tuning of X-linked pigments in humans and New World monkeys, we estimated that the
Ala → Ser, Ile → Phe, Gly → Ser, Phe → Tyr, and Ala → Tyr substitutions at residue positions 180, 229, 233, 277, and 285,
respectively, cause spectral shifts of about 5, −2, −1, 8, and 15 nm. On the other hand, the substitutions His → Tyr, Met
→ Val or Leu, and Ala → Tyr at positions 116, 275, and 276, respectively, have no discernible spectral tuning effect, though
residues 275 and 276 are inside the transmembrane domains. Many substitutions between Val and Ile or between Val and Ala have
occurred in the transmembrane domains among the New World monkey pigment variants but apparently have no effect on spectral
tuning. Our study suggests that, in addition to amino acid changes involving a hydroxyl group, large changes in residue size
can also cause a spectral shift in a visual pigment.
Received: 17 July 1997 / Accepted: 7 December 1997 相似文献
18.
Five cDNAs (pDidact2–pDidact6), representing different actin genes, were isolated from a Diphyllobothrium dendriticum cDNA library, and the DNA as well as the putative amino acid sequences were determined. The corresponding Didact2 and Didact4 genes code for peptides 376 amino acids long, with molecular weights 41,772 and 41,744 Da, respectively, while the deduced
Didact3 protein is 377 amino acids long and weighs 41,912 Da. The pDidact5 and -6 cDNAs lack nucleotides corresponding to three to six amino acids at the amino-terminus. Two of the five cDNAs contain the
conventional AATAAA as the putative polyadenylation signal, one has the common variant ATTAAA, whereas the hexanucleotide
AATAGA is found 15 and 18 nucleotides, respectively, upstream of the poly(A) site in two of the cDNAs. Phylogenetic studies
including 102 actin protein sequences revealed that there are at least four different types of cestode actins. In this study
three of these types were found to be expressed in the adult D. dendriticum tapeworm. Structurally the cestode actin groupings differ from each other to an extent seen only among the metazoan actins
between the vertebrate muscle and cytoplasmic isoforms. In the phylogenetic trees constructed, cestode actins were seen to
map to two different regions, one on the border of the metazoan actins and the other within this group. It is, however, difficult
to say whether the cestode actins branched off early in the metazoan evolution or if this position in the phylogenetic tree
only reflects upon differences in evolutionary rate.
Received: 19 June 1996 / Accepted: 20 August 1996 相似文献
19.
S.I. Ortiz-Miranda J.A. Lasalde P.A. Pappone M.G. McNamee 《The Journal of membrane biology》1997,158(1):17-30
We studied the functional effects of single amino acid substitutions in the postulated M4 transmembrane domains of Torpedo californica nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes at the single-channel level. At low ACh concentrations and cold temperatures, the replacement of wild-type α418Cys
residues with the large, hydrophobic amino acids tryptophan or phenylalanine increased mean open times 26-fold and 3-fold,
respectively. The mutation of a homologous cysteine in the β subunit (β447Trp) had similar but smaller effects on mean open
time. Coexpression of α418Trp and β447Trp had the largest effect on channel open time, increasing mean open time 58-fold.
No changes in conductance or ion selectivity were detected for any of the single subunit amino acid substitutions tested.
However, the coexpression of the α418Trp and β447Trp mutated subunits also produced channels with at least two additional
conductance levels. Block by acetylcholine was apparent in the current records from α418Trp mutants. Burst analysis of the
α418Trp mutations showed an increase in the channel open probability, due to a decrease in the apparent channel closing rate
and a probable increase in the effective opening rate. Our results show that modifications in the primary structure of the
α- and β subunit M4 domain, which are postulated to be at the lipid-protein interface, can significantly alter channel gating,
and that mutations in multiple subunits act additively to increase channel open time.
Received: 27 September 1996/Revised: 28 January 1997 相似文献
20.
Brian R. Francis 《Journal of molecular evolution》2013,77(4):134-158
Fifty years have passed since the genetic code was deciphered, but how the genetic code came into being has not been satisfactorily addressed. It is now widely accepted that the earliest genetic code did not encode all 20 amino acids found in the universal genetic code as some amino acids have complex biosynthetic pathways and likely were not available from the environment. Therefore, the genetic code evolved as pathways for synthesis of new amino acids became available. One hypothesis proposes that early in the evolution of the genetic code four amino acids—valine, alanine, aspartic acid, and glycine—were coded by GNC codons (N = any base) with the remaining codons being nonsense codons. The other sixteen amino acids were subsequently added to the genetic code by changing nonsense codons into sense codons for these amino acids. Improvement in protein function is presumed to be the driving force behind the evolution of the code, but how improved function was achieved by adding amino acids has not been examined. Based on an analysis of amino acid function in proteins, an evolutionary mechanism for expansion of the genetic code is described in which individual coded amino acids were replaced by new amino acids that used nonsense codons differing by one base change from the sense codons previously used. The improved or altered protein function afforded by the changes in amino acid function provided the selective advantage underlying the expansion of the genetic code. Analysis of amino acid properties and functions explains why amino acids are found in their respective positions in the genetic code. 相似文献