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1.
Synonymous and nonsynonymous rate variation in nuclear genes of mammals 总被引:34,自引:6,他引:28
A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes
from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure,
transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the
constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the
48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result
provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and
nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The
differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate
bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates,
and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise
sequence comparison, because more-realistic models about the mutation and substitution processes can be incorporated in the
analysis.
Received: 17 May 1997 / Accepted: 28 September 1997 相似文献
2.
While globin genes ctt-2β and ctt-9.1 in Chironomus thummi thummi each have a single intron, all of the other insect globin genes reported so far are intronless. We analyzed four globin genes
linked to the two intron-bearing genes in C. th. thummi. Three have a single intron at the same position as ctt-2β and ctt-9.1; the fourth is intronless and lies between intron bearing genes. Finally, in addition to its intron, one gene (ctt-13RT) was recently interrupted by retrotransposition. Phylogenetic analyses show that the six genes in C. th. thummi share common ancestry with five globin genes in the distantly related species C. tentans, and that a 5-gene ancestral cluster predates the divergence of the two species. One gene in the ancestral cluster gave rise
to ctn-ORFB in C. tentans, and duplicated in C. th. thummi to create ctt-11 and ctt-12. From parsimonious calculations of evolutionary distances since speciation, ctt-11, ctt-12, and ctn-ORFB evolved rapidly, while ctn-ORFE in C. tentans evolved slowly compared to other globin genes in the clusters. While these four globins are under selective pressure, we
suggest that most chironomid globin genes were not selected for their unique function. Instead, we propose that high gene
copy number itself was selected because conditions favored organisms that could synthesize more hemoglobin. High gene copy
number selection to produce more of a useful product may be the basis of forming multigene families, all of whose members
initially accumulate neutral substitutions while retaining essential function. Maintenance of a large family of globin genes
not only ensured high levels of hemoglobin production, but may have facilitated the extensive divergence of chironomids into
as many as 5000 species.
Received: 31 December 1996 / Accepted: 16 May 1997 相似文献
3.
The rBAT protein, when expressed in Xenopus oocytes, was previously shown to reproduce the selectivity of the Na+-independent neutral and basic amino acid transport system called bo,+. More recently, the capacity of rBAT to generate a transmembrane current was demonstrated when addition of neutral amino
acids stimulated the efflux of cations (presumably basic amino acids) in rBAT-injected oocytes. In the present paper, aminoisobutyric
acid (AIB), a neutral amino acid analogue, was shown to induce outward currents (efflux of basic amino acids) through rBAT
similar to those caused by alanine in terms of affinity, maximal currents and I-V curves. Despite generating similar currents, the AIB transport rate was more than 30 times lower than that of alanine, thus
challenging the assumption that rBAT functions as a classical exchanger. Experiments using a cut-open oocyte voltage clamp
demonstrated that AIB was capable of stimulating rBAT-mediated currents from either side of the membrane. AIB, like alanine,
was able to stimulate the efflux of radiolabeled alanine and arginine while no rBAT-mediated efflux was measurable in the
absence of external rBAT substrates. These results demonstrate that (i) the presence of amino acids is required on both sides
of the membrane for rBAT to mediate amino acid flux and thus rBAT must be some type of exchanger but (ii) rBAT-mediated amino
acid influx is not stoichiometrically related to the efflux. A model of a ``double gated pore' is proposed to account for
these properties of rBAT, which contravene standard models of exchangers and other transporters.
Received: 15 June 1995/Revised: 21 September 1995 相似文献
4.
The influence of the nonchannel conformation of the transmembrane protein gramicidin A on the permeability coefficients of
neutral and ionized α-X-p-methyl-hippuric acid analogues (XMHA) (X = H, OCH3, CN, OH, COOH, and CONH2) across egg-lecithin membranes has been investigated in vesicle efflux experiments. Although 10 mol% gramicidin A increases
lipid chain ordering, it enhances the transport of neutral XMHA analogues up to 8-fold, with more hydrophilic permeants exhibiting
the greatest increase. Substituent contributions to the free energies of transfer of both neutral and anionic XMHA analogues
from water into the bilayer barrier domain were calculated. Linear free-energy relationships were established between these
values and those for solute partitioning from water into decadiene, chlorobutane, butyl ether, and octanol to assess barrier
hydrophobicity. The barrier domain is similar for both neutral and ionized permeants and substantially more hydrophobic than
octanol, thus establishing its location as being beyond the hydrated headgroup region and eliminating transient water pores
as the transport pathway for these permeants, as the hydrated interface or water pores would be expected to be more hydrophilic
than octanol. The addition of 10 mol% gramicidin A alters the barrier domain from a decadiene-like solvent to one possessing
a greater hydrogen-bond accepting capacity. The permeability coefficients for ionized XMHAs increase with Na+ or K+ concentration, exhibiting saturability at high ion concentrations. This behavior can be quantitatively rationalized by Gouy-Chapman
theory, though ion-pairing cannot be conclusively ruled out. The finding that transmembrane proteins alter barrier selectivity,
favoring polar permeant transport, constitutes an important step toward understanding permeability in biomembranes.
Received: 12 July 1999/Revised: 20 October 1999 相似文献
5.
Selective neutrality and enzyme kinetics 总被引:1,自引:0,他引:1
Lloyd Demetrius 《Journal of molecular evolution》1997,45(4):370-377
This article appeals to a recent theory of enzyme evolution to show that the properties, neutral or adaptive, which characterize
the observed allelic variation in natural populations can be inferred from the functional parameters, substrate specificity,
and reaction rate. This study delineates the following relations between activity variables, and the forces—adaptive or neutral—determining
allelic variation: (1) Enzymes with broad substrate specificity: The observed polymorphism is adaptive; mutations in this
class of enzymes can result in increased fitness of the organism and hence be relevant for positive selection. (2) Enzymes
with absolute substrate specificity and diffusion-controlled rates: Observed allelic variation will be absolutely neutral;
mutations in this class of enzymes will be either deleterious or have no effect on fitness. (3) Enzymes with absolute or group
specificity and nondiffusion-controlled rates: Observed variation will be partially neutral; mutants which are selectively
neutral may become advantageous under an appropriate environmental condition or different genetic background. We illustrate
each of the relations between kinetic properties and evolutionary states with examples drawn from enzymes whose evolutionary
dynamics have been intensively studied.
Received: 12 December 1996 / Accepted: 22 April 1997 相似文献
6.
Weinreich DM 《Journal of molecular evolution》2001,52(1):40-50
A higher rate of molecular evolution in rodents than in primates at synonymous sites and, to a lesser extent, at amino acid
replacement sites has been reported previously for most nuclear genes examined. Thus in these genes the average ratio of amino
acid replacement to synonymous substitution rates in rodents is lower than in primates, an observation at odds with the neutral
model of molecular evolution. Under Ohta's mildly deleterious model of molecular evolution, these observations are seen as
the consequence of the combined effects of a shorter generation time (driving a higher mutation rate) and a larger effective
population size (resulting in more effective selection against mildly deleterious mutations) in rodents. The present study
reports the results of a maximum-likelihood analysis of the ratio of amino acid replacements to synonymous substitutions for
genes encoded in mitochondrial DNA (mtDNA) in these two lineages. A similar pattern is observed: in rodents this ratio is
significantly lower than in primates, again consistent only with the mildly deleterious model. Interestingly the lineage-specific
difference is much more pronounced in mtDNA-encoded than in nuclear-encoded proteins, an observation which is shown to run
counter to expectation under Ohta's model. Finally, accepting certain fossil divergence dates, the lineage-specific difference
in amino acid replacement-to-synonymous substitution ratio in mtDNA can be partitioned and is found to be entirely the consequence
of a higher mutation rate in rodents. This conclusion is consistent with a replication-dependent model of mutation in mtDNA.
Received: 24 September 1999 / Accepted: 18 September 2000 相似文献
7.
Rachid Safi Agnès Begue Catherine Hänni Dominique Stehelin Jamshed R. Tata Vincent Laudet 《Journal of molecular evolution》1997,44(6):595-604
Since thyroid hormones play a pivotal role in amphibian metamorphosis we used PCR to amplify DNA fragments corresponding
to a portion of the ligand-binding domain of the thyroid hormone receptor (TR) genes in several neotenic amphibians: the obligatory
neotenic members of the family Proteidea the mudpuppy Necturus maculosus and Proteus anguinus as well as two members of the facultative neotenic Ambystoma genus: the axolotl Ambystoma mexicanum and the tiger salamander Ambystoma tigrinum. In addition, we looked for TR genes in the genome of an apode Typhlonectes compressicaudus. TR genes were found in all these species including the obligatory neotenic ones. The PCR fragments obtained encompass both
the C and E domains and correspond to α and β genes. Their sequences appear to be normal, suggesting that there is no acceleration
of evolutionary rates in the TR genes of neotenic amphibians. This result is not surprising for Ambystomatidae, which are
known to respond to T3 (3,3′,5-triiodothyronine) but is not in agreement with biochemical and biological data showing that
Proteidea cannot respond to thyroid hormones. Interestingly, by RT-PCR analysis we observed a high expression levels of TRα
in gills, intestine, and muscles of Necturus as well as in the liver of Ambystoma mexicanum, whereas TRβ expression was only detected in Ambystoma mexicanum but not in Necturus. Such a differential expression pattern of TRα and TRβ may explain the neoteny in Proteidea. The cloning of thyroid-hormone-receptor
gene fragments from these species will allow the molecular study of their failure to undergo metamorphosis.
Received: 23 April 1996 / Accepted: 20 January 1997 相似文献
8.
To evaluate the relative importance of positive selection and neutral drift from the nucleotide base changes observed in
the homologous alignment of genes, a theoretical equation of base changes is formulated by including both the influence of
selection and the base substitutions due to mutations. Under the assumption that the average rate of base substitutions estimated
from synonymous changes is the ``true' mutation rate applicable at all positions, this method is applied to the vertebrate
globin gene family, and evaluates the departures of base change rates from the ``true' mutation rate at the first and second
codon positions as a consequence of preferential selection for the conservation of important function. In addition to the
strong effect of selection on the amino acid residues in the internal region mostly common to myoglobin and hemoglobin chains,
the distinctive directions of selective parameter values are seen at sites on the globin surface, distinguishing the subunit
contact residues of hemoglobins from the polar residues on the surface of myoglobins. Moreover, this effect of selection distinguishing
between the myoglobin and hemoglobin chain genes becomes weaker in cold-blooded vertebrates, especially in fish, strongly
suggesting the possibility that the clear distinction between these globins is a result of selection out of the changes regarded
as neutral ones in an ancestor of vertebrates. Thus, the present method may also serve to investigate the homology of many
other proteins from the aspect of molecular evolution, mainly focusing on the evolution of their biological functions.
Received: 2 January 1996 / Accepted: 20 February 1997 相似文献
9.
Synonymous substitution rates in mitochondrial and nuclear genes of Drosophila were compared. To make accurate comparisons, we considered the following: (1) relative synonymous rates, which do not require
divergence time estimates, should be used; (2) methods estimating divergence should take into account base composition; (3)
only very closely related species should be used to avoid effects of saturation; (4) the heterogeneity of rates should be
examined. We modified the methods estimating synonymous substitution numbers to account for base composition bias. By using
these methods, we found that mitochondrial genes have 1.7–3.4 times higher synonymous substitution rates than the fastest
nuclear genes or 4.5–9.0 times higher rates than the average nuclear genes. The average rate of synonymous transversions was
2.7 (estimated from the melanogaster species subgroup) or 2.9 (estimated from the obscura group) times higher in mitochondrial genes than in nuclear genes. Synonymous transversions in mitochondrial genes occurred
at an approximately equivalent rate to those in the fastest nuclear genes. This last result is not consistent with the hypothesis
that the difference in turnover rates between mitochondrial and nuclear genomes is the major factor determining higher synonymous
substitution rates in mtDNA. We conclude that the difference in synonymous substitution rates is due to a combination of two
factors: a higher transitional mutation rate in mtDNA and constraints on nuclear genes due to selection for codon usage.
Received: 27 November 1996 / Accepted: 8 May 1997 相似文献
10.
Bickel DR 《Journal of molecular evolution》2000,50(4):381-390
Many tests of the lineage dependence of substitution rates, computations of the error of evolutionary distances, and simulations
of molecular evolution assume that the rate of evolution is constant in time within each lineage descended from a common ancestor.
However, estimates of the index of dispersion of numbers of mammalian substitutions suggest that the rate has time-dependent
variations consistent with a fractal-Gaussian-rate Poisson process, which assumes common descent without assuming rate constancy.
While this model does not affect certain relative-rate tests, it substantially increases the uncertainty of branch lengths.
Thus, fluctuations in the rate of substitution cannot be neglected in calculations that rely on evolutionary distances, such
as the confidence intervals of divergence times and certain phylogenetic reconstructions. The fractal-Gaussian-rate Poisson
process is compared and contrasted with previous models of molecular evolution, including other Poisson processes, the fractal
renewal process, a Lévy-stable process, a fractional-difference process, and a log-Brownian process. The fractal models are
more compatible with mammalian data than the nonfractal models considered, and they may also be better supported by Darwinian
theory. Although the fractal-Gaussian-rate Poisson process has not been proven to have better agreement with data or theory
than the other fractal models, its Gaussian nature simplifies the exploration of its impact on evolutionary distance errors
and relative-rate tests.
Received: 29 September 1999 / Accepted: 20 January 2000 相似文献