*MRC Laboratory for Molecular Cell Biology and
Department of Biology, University College London, London, England;
and
Institute of Zoology, London, England
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Abstract |
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Introduction |
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Although the subcellular distribution of AGT appears to be highly variable when different species are compared, its distribution within a particular species does not normally change, and correct localization is absolutely critical for an animal's survival. This is best exemplified by the human hereditary disease primary hyperoxaluria type 1 (PH1), a lethal condition caused by a functional deficiency of AGT (Danpure and Purdue 1995
). Although in most normal humans, AGT is entirely peroxisomal, in a subset of PH1 patients it is mistargeted to mitochondria (Danpure et al. 1989
). Although catalytically active in the mitochondria, AGT is unable to fulfil its metabolic role of glyoxylate detoxification in this organelle.
Notwithstanding the above, in a very restricted group of rodents (e.g., rats, mice, and hamsters), but not in most other species (e.g., guinea pigs, rabbits, dogs and cats), the distribution of AGT can be modified by exogenous stimuli. For example, the normally mitochondrial and peroxisomal distribution of AGT found in the liver cells of murine rodents can be modified to become mainly mitochondrial by the administration of gluconeogenic stimuli, such as glucagon or high-protein diets (Hayashi, Sakuraba, and Noguchi 1989
; Oda, Yanagisawa, and Ichiyama 1982
).
There is a clear relationship between the organellar distribution of AGT and diet (Danpure et al. 1990, 1994
). Thus, there is a tendency for AGT to be peroxisomal in herbivores, mitochondrial in carnivores, and both peroxisomal and mitochondrial in omnivores. It has been suggested that the dual distribution of AGT might be related to its putative dual metabolic role of gluconeogenesis (in the mitochondria) and glyoxylate detoxification (in the peroxisomes). For reasons discussed previously, it is likely that the former is the principal role of AGT in carnivores and the latter is its main role in herbivores (Danpure et al. 1990, 1994
).
The single AGT gene has been cloned and functionally characterized in the human (Homo sapiens), the common marmoset (Callithrix jacchus), the rabbit (Oryctolagus cuniculus), the cat (Felis catus), the rat (Rattus norvegicus), and the guinea pig (Cavia porcellus) (Oda et al. 1987
; Takada et al. 1990
; Nishiyama et al. 1990
; Oda, Funai, and Ichiyama 1990
; Purdue, Lumb, and Danpure 1992
; Lumb, Purdue, and Danpure 1994
; Oatey, Lumb, and Danpure 1996
; Birdsey and Danpure 1998
). Such studies have shown that the archetypal mammalian AGT gene (see fig. 1 ) has the potential to encode an N-terminal mitochondrial targeting presequence (MTS) and a C-terminal peroxisomal targeting sequence type 1 (PTS1) (Motley et al. 1995
) by the variable use of two transcription and two translation initiation sites (Danpure 1997
). The final intracellular destination of AGT is dependent on the expression of the MTS rather than that of the PTS1, with the former being functionally dominant over the latter (Oatey, Lumb, and Danpure 1996
). Thus, a decrease in mitochondrial targeting can automatically lead to an increase in peroxisomal targeting.
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Within Mammalia, some orders have the same distribution of AGT in all members; for example, all the species of Insectivora studied have mainly mitochondrial AGT. However, some closely related species differ in their AGT distributions. One group for which this is apparent is primates, which have provided the focus for this study. The distribution of hepatic AGT in primates appears to clearly separate the Platyrrhini from the Catarrhini. With the exception of the saki monkey (Pithecia pithecia), the Platyrrhini have the putatively more ancestral AGT distribution (i.e., mitochondrial and peroxisomal), also found in the Prosimii (Danpure et al. 1994
). However, the Catarrhini have an exclusively peroxisomal distribution. From our previous studies on the molecular basis of AGT targeting in the human and the common marmoset, we have suggested that the loss of the 5' translation start site in the human ancestral line probably occurred soon after the separation of the Platyrrhini and Catarrhini lineages (Danpure 1997
).
In the present study, we investigated further the molecular evolution of AGT targeting in Anthropoidea. We determined the nucleotide sequence of the 5' part of the AGT gene, including the regions containing both of the ancestral translation initiation sites, for 11 primates. We subjected these, along with the two primate sequences previously known, to a variety of analyses in an attempt to determine the nature of the mutational events, and their temporal relationships, which have led to the differences in AGT targeting within Anthropoidea.
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Materials and Methods |
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Polymerase Chain Reaction
The PCR primers P1 (5'-AAGCCCATCCACCAATCCTCN-3'), P2 (5'-CTGGAACACGTACTGGATCCCTTCCTTGAN-3'), and P3 (5'-AGGGGCTTGAGCAGGGCCTTG-3') were designed to map to regions of high sequence identity. P1 (+ strand) maps to 5332 bp upstream of the 5' ancestral translation start (site 1 in fig. 1
). P2 (- strand) maps to 1241 bp downstream of the intron A/exon 2 boundary. P3 (- strand) maps to 3252 bp downstream of the 3' ancestral translation start site (site 2 in fig. 1
). Primer pair P1/P2 was designed to amplify a region of the AGT gene containing all of exon 1 (including both ancestral translation start sites), intron A, and part of exon 2 (see fig. 1
). Amplification of intron A was considered important to minimize the possibility of unrecognized interspecies cross contamination. In two cases in which amplification with P1/P2 was unsuccessful, amplification was achieved with primer pair P1/P3, which gave a shorter product that excluded intron A (see fig. 1
).
The 5' regions of the AGT gene were amplified by PCR with a hot start at 80°C for 3 min, followed by 35 cycles of 30 s at 94°C, 30 s at 5565°C, and 45 s at 72°C, followed by a final extension period of 15 min at 72°C. Samples (50 µl) contained 75 µM MgCl2 and 10 µM dNTPs.
Cloning and Sequencing
The PCR products were cloned into the pGEM-T Easy plasmid (Promega) and sequenced by the dideoxy method using Sequenase version 2.0 T7 DNA polymerase (Amersham Life Science). In some cases, cycle sequencing was carried out with the ABI PRISM Big Dye Terminator Cycle Sequencing Ready Reaction kit (Perkin-Elmer). The sequences described in this paper have been deposited in the EMBL database under accession numbers AJ237886 (Ptr), AJ237887 (Ggo), AJ237888 (Hla), AJ237889 (Pan), AJ237890 (Mni), AJ237891 (Cdi), AJ237892 (Lro), AJ237893 (Cgo), AJ237894 (Ssc), AJ237895 (Ppi), and AJ237896 (Apa).
Data Analysis
Nucleotide sequences were aligned using Pileup (Devereux, Haeberli, and Smithies 1984
) and CLUSTAL W (Thompson, Higgins, and Gibson 1994
). Ancestral states were reconstructed by a codon-based maximum-likelihood analysis using marginal reconstruction of ancestral sequences (Yang, Kumar, and Nei 1995
). The pairwise estimates of synonymous and nonsynonymous mutations per synonymous and nonsynonymous site (i.e., dS and dN) were calculated by the maximum-likelihood method of Goldman and Yang (1994)
. Estimation of dN/dS (
) among lineages by maximum likelihood was performed by the method of Yang (1998)
using the computer program PAML (version 2, freely available at http://abacus.gene.ucl.ac.uk/software/paml.html). Likelihood ratio tests were used to compare models, with the
2 distribution used as an approximation.
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Results |
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The nucleotide sequences of the P1/P2 products (excluding intron A and exon 2) and the P1/P3 PCR products are shown in figure 2 , and their deduced amino acid sequences are shown in figure 3 . As expected, the amplified regions were very similar to each other at both the nucleotide and the amino acid levels. Following pairwise comparisons, the nucleotide identity of region 1 (defined as nucleotides -66 to -1 and amino acids -22 to -1, with potential to encode, or act as, a MTS) varied between 78% and 100%, while the amino acid identity varied between 62% and 100%. In this region, there was a 61% nucleotide identity and a 33% amino acid identity across all 13 primates. Pairwise comparisons of region 2 (defined as nucleotides +1 to +165 and amino acids +1 to +55, where available) showed that the nucleotide identity varied between 81% and 100% and the amino acid identity varied between 67% and 100%. Excluding the missing nucleotides and residues in this region, the overall nucleotide identity was 62% and the overall amino acid identity was 48%. Overall, the levels of conservation (i.e., sequence identity) of regions 1 and 2 appear to be similar, despite the likelihood that region 1 is frequently excluded from the open reading frame (see Introduction). In fact, based on the absence of the 5' ancestral start site (figs. 2 and 3 ), the ancestral MTS would appear to be excluded from the open reading frame in five of the seven catarrhines studied (i.e., the human, the chimpanzee, the gorilla, the gibbon, and the Diana monkey) and one out of the six platyrrhines (i.e., the saki monkey).
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The values for dN plotted against those for dS in region 1 (which would be expected to be under variable selection pressure because it can be included or excluded from the open reading frame) and region 2 (which would be expected to be under continuous functional constraint because it is always included in the open reading frame) are shown in figure 5 . The 5' ancestral translation start codon was excluded from the dN and dS analysis of region 1 (designated as region 1*) because of its unique position in determining whether the remainder of the region is included within the open reading frame or not. In addition, any change to this codon from the ancestral condition would exclude this site from the open reading frame, and therefore the terms synonymous and nonsynonymous would have no meaning in this context.
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Analysis of the dN/dS Ratios Among Lineages Indicates Positive Pressure Acting on Region 1 in Several Recent Anthropoid Branches but Not on the Ancestral Branch Linking Catarrhines with Platyrrhines
In order to determine the evolutionary basis of the differences in dN/dS ratios obtained by pairwise comparisons (see above), we used the likelihood ratio test to calculate dN/dS ratios among the different lineages (fig. 6
) (Yang 1998
). The data were fitted to various models of sequence evolution, and the models were compared by the likelihood ratio test using the
2 approximation (tables 3 and 4
).
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A model that assumes the same ratio for all branches (the "one-ratio" model) gave
= 2.00. To test whether this
ratio is significantly greater than 1, we compared it with a one-ratio model in which
was fixed at 1. When the likelihood ratio statistic (2
) was compared with the
2 distribution, the difference between the models was not significant (P = 0.110) (see tables 3 and 4
).
In order to test our hypothesis (based on our subjective assessment of the data to date) that positive selection has been driving only the recent evolution of region 1*, we fitted a "two-ratio" model, which assumes that the ancestral branch joining the Catarrhini with the Platyrrhini (i.e., branch 13) has an ratio (
0) that is different from that of all the other (more recent) branches (
1). The two-ratio model fits the data of region 1* significantly better than the one-ratio model (P = 0.0014), and it follows that
ratios are significantly different between the old (branch 13) and recent (branches 2, 46, 8, 10, 16, 18, 19, 22, and 23) lineages. Furthermore, we found that
1 for these recent lineages was significantly different from (greater than) 1 (P = 0.0038) (see table 4
).
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Discussion |
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In addition to the absence of the 5' ancestral translation start site in humans (Takada et al. 1990
), we have shown in the present study that it is also absent in the following catarrhinesthe common chimpanzee, the common gorilla, the white-handed gibbon, and the Diana monkey, as well as the white-faced saki monkey, which is a platyrrhine (see figs. 2 and 3
). Of these, the human, the chimpanzee, the gorilla and the saki monkey are known to have a peroxisomal distribution of AGT (Danpure et al. 1994
; unpublished observations). The subcellular distribution of AGT in the gibbon and the Diana monkey is not known. In addition to the presence of the 5' ancestral translation start site in the common marmoset (Purdue, Lumb, and Danpure 1992
), we have shown in this study that it is also present in the black spider monkey, the golden lion tamarin, the goeldis monkey, and the common squirrel monkey (all platyrrhines), as well as the anubis baboon and the Celebes macaque (both catarrhines) (see figs. 2 and 3 ). AGT is known to be both mitochondrial and peroxisomal in the marmoset and yet peroxisomal in the baboon. The distribution in the other species is unknown, but as all Callitrichidae studied to date have both mitochondrial and peroxisomal AGT, it is likely that the golden lion tamarin, the goeldis monkey, and the common squirrel monkey do as well. In addition, it is likely that Celebes macaque has peroxisomal AGT, as its close relative the Japanese macaque does also (Takada and Noguchi 1982
). Unfortunately, there are no clues to the subcellular distribution of AGT in the black spider monkey.
With the notable exception of two of the Cercopithecidae, the anubis baboon and the Celebes macaque, the sequences at the 5' ancestral translation start sites in the primate AGT genes studied in this paper are compatible with the known or likely subcellular distributions of AGT. Thus, when the triplet ATG is present at this site, AGT is both mitochondrial and peroxisomal. However, when any other sequence (e.g., ATA, ATC, GTG, or CTG in this study) is present at this site, AGT is only peroxisomal. Thus, in most of the primates studied, loss of mitochondrial AGT targeting is due to loss of the 5' translation start site and hence the exclusion of the region encoding the MTS from the open reading frame, as advocated previously (Danpure 1997
). Clearly, this cannot be the case for the baboon and the macaque, which must have lost mitochondrial AGT targeting by a different mechanism.
Mitochondrial AGT Has Been Lost in the Baboon and the Macaque, Probably by Loss of the 5' Ancestral Transcription Start Site
There are at least two possible mechanisms by which the baboon and the macaque could have lost the ability to target AGT to the mitochondria without loss of the 5' translation start site. They could have lost the 5' transcription start site (site A in fig. 1
), or they could have accumulated nonsynonymous mutations in the MTS that prevent it from functioning as such. Loss of the 5' transcription start site, which is upstream of both translation start sites, would result in the exclusion of region 1 (encoding the MTS) from the open reading frame, as does the loss of the 5' translation start site. The 5' transcription start site has been lost in the guinea pig, which has also lost the ability to target AGT to the mitochondria, but this could be a secondary event to the putative earlier loss of the 5' translation start site (Birdsey and Danpure 1998
).
On the assumption that region 1 is contained within the open reading frame in the baboon and the macaque, the deduced amino acid sequence shows a number of differences from those expected for an efficient MTS, which are usually positively charged amphiphilic -helices (von Heijne 1986
). For example, Arg(-2) and Arg(-8) have both been replaced by Gln (fig. 3
). This would not only decrease substantially the net positive charge of the sequence, but the loss of Arg(-2) would also be predicted to interfere with presequence cleavage (Schneider et al. 1998
). In addition, the presence of three juxtaposed helix breakers, Pro(-11), Gly(-10), and Pro(-9), would call into question the ability of this region to fold into an
-helix.
Although both of the mechanisms proposed for the loss of mitochondrial targeting in the baboon and the macaque are possible, we consider that the former is most likely (i.e., the loss of the 5' transcription start site), because our previous studies (Danpure et al. 1990
) and recent unpublished observations show that AGT in the baboon liver is similar in size to human AGT (i.e., it lacks the 22-aa mitochondrial leader sequence). Although it is conceivable that baboon AGT could be initially targeted to mitochondria, have its leader MTS (encoded by region 1) cleaved by the mitochondrial processing peptidase, and then be released back into the cytosol for subsequent import into peroxisomes (by a mechanism like that proposed for Saccharomyces cerevisiae fumarase [Stein et al. 1994
]), it seems improbable to us, at least. If our conclusions are correct, then this is the first example of the loss of mitochondrial AGT targeting caused by loss of the 5' transcription start site (site A in fig. 1
).
Possible Temporal Relationship of the Mutational Events Leading to the Varied Subcellular Distribution of AGT in Extant Primates
So far, there is evidence for only one platyrrhine having lost mitochondrial AGT targeting (i.e., the saki monkey), and this is clearly independent of the loss of mitochondrial AGT targeting in the Catarrhini. In addition, the saki monkey is the only platyrrhine in which the 5' ancestral translation start site has been lost. As region 1 in the saki monkey also contains a stop codon, it is not possible to determine whether the loss of the 5' translation start was the primary event and the acquisition of stop codon a neutral secondary event or vice versa. Nevertheless, both of these changes probably occurred after the separation of the saki monkey and the spider monkey ancestral lines about 23 MYA (see fig. 4
).
The situation for the Catarrhini appears to be much more complicated. Although, as is so far known, the distribution of AGT in the Catarrhini is uniform (i.e., peroxisomal), our molecular analysis and ancestral reconstruction suggests the possibility of four different reasons, namely mutation of the 5' ancestral translation start site to ATA in the human, the chimpanzee and the gorilla, to ATC in the gibbon, and to GTG in the Diana monkey, and the loss of the 5' transcription start site in the baboon and the macaque. The difficulty is in determining which events in the evolutionary history of the Catarrhini had functional consequences (i.e., led to the loss of mitochondrial targeting) and which were neutral secondary consequences of an earlier event that led to the loss of mitochondrial targeting (see fig. 4 ).
This is especially the case for the Diana monkey, the more recent ancestral branches (i.e., 8 and 10) of which contain six nonsynonymous mutations, as well as the loss of the 5' translation start site (fig. 4 ). Superimposed on this already complex situation is the predicted loss of the 5' transcription start site in the baboon/macaque ancestral lineage, which presumably could have occurred in branches 8 or 9 (see fig. 4 ). Because the cell biological effects of the various amino acid substitutions found in the ancestral MTS are not currently known with certainty, and because their temporal relationships can never be known with certainty, the precipitating event (i.e., that which actually causes loss of mitochondrial AGT targeting) can only be surmised.
Notwithstanding these difficulties, it is likely that mitochondrial AGT targeting has been lost on at least four or five occasions in anthropoid evolution.
Positive Selection Pressure to Lose Mitochondrial Targeting Has Been Widespread in the Recent Evolutionary History of Anthropoids
One of the difficulties in determining the sequence of molecular events that have led to the variable distribution of AGT in primates is an inability to understand the nature of, and to quantify, the selection pressures that might have led to the changes. Ratios of dN/dS greater than 1 are often taken as evidence of positive selection pressure (i.e., pressure for change) acting on a sequence of interest (Messier and Stewart 1997
). All our analyses point to region 1 (i.e., the MTS or the region encoding the MTS) behaving very differently from region 2 (see figs. 46 ).
When region 1 is included in the open reading frame, it has a function (i.e., directs the targeting of AGT to the mitochondria). It might, therefore, be expected to be evolutionarily constrained, preventing it from acquiring features that interfere with its function. Equally, when this region is excluded from the open reading frame, it is presumed to have no function and therefore would not be so constrained. In the first case, dN would be expected to be less than dS. In the second case, it would be expected that there would be no difference in the values of dN and dS. On the other hand, if there was selection pressure to interfere with the function of region 1 while it was still in the open reading frame (i.e., to diminish its effectiveness as an MTS), then at stages in evolutionary history it might be expected that dN would be greater than dS.
There are many more pairwise comparisons in which dN/dS is greater than 1 in region 1* than there are in region 2 (fig. 5 ). In addition, dN/dS > 1 is much more common when region 1* is compared between closely related species than when it is compared between distantly related species. This might suggest that the pressures on the MTS might be different in ancient anthropoid evolutionary history compared with more recent evolutionary history. In other words, ancient pressure to conserve mitochondrial AGT targeting might have led to more recent pressure to lose it. If this is generally true, then the Catarrhini would appear to have been more "successful" than the Platyrrhini at succumbing to that pressure.
Estimation of dN/dS ratios among lineages gives a slightly different, but not incompatible, picture (fig. 6
). In region 1*, 8 of the more recent branches have dN/dS > 1, 3 branches have dN/dS < 1 (although only slightly so in two), and 11 branches have no substitutions at all. Significantly, the ancestral branch joining the Catarrhini to the Platyrrhini had a dN/dS ratio very much lower than one. Statistical analysis confirmed the ancient/recent divide, although clearly not all recent branches show evidence of positive selection pressure. Thus, the adaptive evolution of the region encoding the ancestral MTS of AGT would appear to be episodic, as has been found before with primate lysozyme (Messier and Stewart 1997
), but with the adaptive changes being concentrated in more recent lineages.
There are two major difficulties with such analyses, one unique to the MTS of AGT and one more generally applicable to the comparison of short, closely related sequences. First, pressure to lose or diminish mitochondrial AGT targeting could result in two consequences at the sequence level(1) loss of the 5' ancestral translation start site, and (2) changes in the amino acid sequence which adversely affect the ability of the ancestral MTS to provide adequate topogenic information. The latter is likely to be an incremental stochastic process and could result in high dN/dS ratios. This would be typical of the situation in almost all other proteins studied in which positive selection pressure has been shown to occur. However, the former is an instantaneous switch and would not be reflected in the dN/dS ratios. Therefore, high dN/dS ratios resulting from positive selection pressure can only occur while the MTS and the 5' translation start site still exist. Once the translation start site has been lost, any changes to the region (except perhaps those that might reinstate the MTS) would be expected to be neutral.
Molecular analysis of the anthropoid lineages clearly shows that there is a relationship between the branches with high dN/dS ratios (fig. 6 ) and those in which amino acid replacements are predicted to have occurred (fig. 4 ). The exceptions are branches 5 and 6, but even in these cases, dN/dS > 1 if the 5' initiating methionine is included in the analysis (data not shownsee rationale for excluding this codon from the dN/dS analyses in the Results section). Therefore, it is possible that in branches where the 5' translation start site has been predicted to have been lost (i.e., branches 5, 6, 10, and 22; see fig. 4 ), the high dN/dS ratios reflect positive selection pressure to diminish the effectiveness of the MTS before it was lost completely. Why some branches downstream of others in which the 5' translation start site has been lost should still have dN/dS > 1 (i.e., branches 2 and 4) is unclear (but see the threshold effect below).
The second difficulty with analyses such as these is a general problem associated with the comparison of small sequences (only 63 nucleotides in the case of region 1*) in closely related species in which only relatively few mutational events have occurred. This is especially noticeable when region 1* is compared within the Platyrrhini, where dS in most comparisons is zero (fig. 5
). This situation is not found in region 2. Although marked differences in dS across individual genes have been found before (Endo, Ikeo, and Gojobori 1996
; Alvarez-Valin, Jabbari, and Bernardi 1998
), the reasons remain unclear. As the total number of nonsynonymous sites is usually greater than the number of synonymous sites, a threshold effect could artifactually elevate the dN/dS ratio in very closely related short sequences. Although this could conceivably contribute to the high dN/dS ratio when the Platyrrhini are compared with each other, it is less likely to contribute significantly to the high dN/dS ratio when the Catarrhini are compared with each other.
The Nature of the Selection Pressure Determining AGT Targeting in Primates
Although molecular adaptation is predicted to be a consequence of Darwinian natural selection, there are surprisingly few examples in the literature of it actually having occurred (Golding and Dean 1998
). Based on dN/dS > 1, only relatively few genes, or parts of genes, show any evidence of having been the subject of positive selection pressure (Endo, Ikeo, and Gojobori 1996
). Some of the best known examples of genes, or parts of genes, that do show such pressure include primate lysozymes (Messier and Stewart 1997
), the antigen recognition sites of MHC genes (Hughes, Ota, and Nei 1990
), the surface antigens of parasites and viruses (Endo, Ikeo, and Gojobori 1996
), and abalone fertilization proteins (Vacquier, Swanson, and Lee 1997
). Even though sequence comparisons might provide strong evidence of positive selection pressure, it is not always easy to identify what that selection pressure actually is.
There are a number of metabolic reasons for suggesting that diet is the best candidate for the pressure to lose, or decrease the efficiency of, mitochondrial AGT targeting in Mammalia as a whole (Danpure et al. 1994
), but whether dietary selection pressure is also responsible for the predicted frequent loss of mitochondrial targeting in Anthropoidea (especially the Catarrhini) is much less clear. Our previous studies on mammals, which included carnivores (including insectivores), herbivores (including frugivores and folivores), omnivores, and almost all combinations, suggested that the optimal distribution of AGT was mitochondrial in carnivores, peroxisomal in herbivores, and both mitochondrial and peroxisomal in omnivores. Unfortunately, the dietary range in Primates, most of which are opportunistic omnivores, is much smaller (see fig. 7
) (Kay 1984
). Nevertheless, there appears to be a weak relationship between diet and AGT distribution (or the presence or absence of the 5' ancestral translation start site) in Primates. For example, insectivorous primates tend to have both mitochondrial and peroxisomal AGT, whereas frugivorous or folivorous primates can have AGT either in both organelles or only in peroxisomes. However, it is not clear whether there is any rational metabolic basis for this dietary relationship in Primates as there is for Mammalia as a whole (Danpure et al. 1994
).
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Thus, although the nature of the evolutionary selection pressure leading to changes in AGT distribution in Anthropoidea is less easily identified than it is within Mammalia as a whole, it is clear that the variable compartmentalization of AGT is a unique and remarkable example of molecular adaptation as a consequence of positive (probably dietary) selection pressure.
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Acknowledgements |
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Footnotes |
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1 Present address: Centre for Clinical Pharmacology, The Rayne Institute, University College London, London, England.
2 Present address: Cardiff School of Biosciences, Cardiff University, Cardiff, Wales.
3 Keywords: molecular adaptation
alanine : glyoxylate aminotransferase
dietary selection pressure
protein targeting
mitochondria
peroxisomes.
4 Address for correspondence and reprints: Christopher J. Danpure, MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom. E-mail: c.danpure{at}ucl.ac.uk
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literature cited |
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![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
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Alvarez-Valin, F., K. Jabbari, and G. Bernardi. 1998. Synonymous and nonsynonymous substitutions in mammalian genes: intragenic correlations. J. Mol. Evol. 46:3744.[ISI][Medline]
Birdsey, G. M., and C. J. Danpure. 1998. Evolution of alanine : glyoxylate aminotransferase intracellular targeting. Structural and functional analysis of the guinea pig gene. Biochem. J. 331:4960.[ISI][Medline]
Danpure, C. J. 1995. How can the products of a single gene be localized to more than one intracellular compartment? Trends Cell Biol. 5:230238.
. 1997. Variable peroxisomal and mitochondrial targeting of alanine : glyoxylate aminotransferase in mammalian evolution and disease. Bioessays 19:317326.
Danpure, C. J., P. J. Cooper, P. J. Wise, and P. R. Jennings. 1989. An enzyme trafficking defect in two patients with primary hyperoxaluria type 1: peroxisomal alanine/glyoxylate aminotransferase rerouted to mitochondria. J. Cell Biol. 108:13451352.[Abstract]
Danpure, C. J., P. Fryer, P. R. Jennings, J. Allsop, S. Griffiths, and A. Cunningham. 1994. Evolution of alanine : glyoxylate aminotransferase 1 peroxisomal and mitochondrial targeting. A survey of its subcellular distribution in the livers of various representatives of the classes Mammalia, Aves and Amphibia. Eur. J. Cell Biol. 64:295313.[ISI][Medline]
Danpure, C. J., K. M. Guttridge, P. Fryer, P. R. Jennings, J. Allsop, and P. E. Purdue. 1990. Subcellular distribution of hepatic alanine : glyoxylate aminotransferase in various mammalian species. J. Cell Sci. 97:669678.[Abstract]
Danpure, C. J., and P. E. Purdue. 1995. Primary hyperoxaluria. Pp. 23852424 in C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, eds. The metabolic and molecular bases of inherited disease. McGraw-Hill, New York.
Devereux, J., P. Haeberli, and O. Smithies. 1984. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 12:387395.[Abstract]
Endo, T., K. Ikeo, and T. Gojobori. 1996. Large-scale search for genes on which positive selection may operate. Mol. Biol. Evol. 13:685690.[Abstract]
Fleagle, J. G. 1988. Primate adaptation and evolution. Academic Press, San Diego.
Fleagle, J. G., and R. F. Kay. 1985. The paleobiology of catarrhines. Pp. 2336 in E. Delson, ed. Ancestors: the hard evidence. Alan R. Liss, New York.
Golding, G. B., and A. M. Dean. 1998. The structural basis of molecular adaptation. Mol. Biol. Evol. 15:355369.[Abstract]
Goldman, N., and Z. Yang. 1994. A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol. Biol. Evol. 11:725736.
Harvey, P. H., R. D. Martin, and T. H. Clutton-Brock. 1987. Life histories in comparative perspective. Pp. 181196 in B. B. Smuts, D. L. Cheney, R. M. Seyfarth, R. W. Wrangham, and T. T. Struhsaker, eds. Primate societies. University of Chicago Press, Chicago.
Hayashi, S., H. Sakuraba, and T. Noguchi. 1989. Response of hepatic alanine : glyoxylate aminotransferase 1 to hormone differs among mammalia. Biochem. Biophys. Res. Commun. 165:372376.[ISI][Medline]
Hughes, A. L., T. Ota, and M. Nei. 1990. Positive Darwinian selection promotes charge profile diversity in the antigen-binding cleft of class I major-histocompatibility-complex molecules. Mol. Biol. Evol. 7:515524.[Abstract]
Kay, R. F. 1984. On the use of anatomical features to infer foraging behaviours in extinct primates. Pp. 2153 in P. S. Rodman and J. G. Cant, eds. Adaptations for foraging in nonhuman primates. Columbia University Press, New York.
Kay, R. F., and E. L. Simons. 1980. The ecology of oligocene African Anthropoidea. Int. J. Primatol. 1:2137.
Lumb, M. J., P. E. Purdue, and C. J. Danpure. 1994. Molecular evolution of alanine/glyoxylate aminotransferase 1 intracellular targeting: analysis of the feline gene. Eur. J. Biochem. 221:5362.[Abstract]
Messier, W., and C. B. Stewart. 1997. Episodic adaptive evolution of primate lysozymes. Nature 385:151154.
Miyajima, H., T. Oda, and A. Ichiyama. 1989. Induction of mitochondrial serine : pyruvate aminotransferase of rat liver by glucagon and insulin through different mechanisms. J. Biochem. Tokyo 105:500504.
Motley, A., M. J. Lumb, P. B. Oatey, P. R. Jennings, P. A. De Zoysa, R. J. Wanders, H. F. Tabak, and C. J. Danpure. 1995. Mammalian alanine : glyoxylate aminotransferase 1 is imported into peroxisomes via the PTS1 translocation pathway. Increased degeneracy and context specificity of the mammalian PTS1 motif and implications for the peroxisome-to-mitochondrion mistargeting of AGT in primary hyperoxaluria type 1. J. Cell Biol. 131:95109.[Abstract]
Nishiyama, K., G. Berstein, T. Oda, and A. Ichiyama. 1990. Cloning and nucleotide sequence of cDNA encoding human liver serine-pyruvate aminotransferase. Eur. J. Biochem. 194:918.[Abstract]
Nowak, R. M. 1991. Walker's mammals of the world. John Hopkins University Press, Baltimore.
Oatey, P. B., M. J. Lumb, and C. J. Danpure. 1996. Molecular basis of the variable mitochondrial and peroxisomal localisation of alanine : glyoxylate aminotransferase. Eur. J. Biochem. 241:374385.[Abstract]
Oda, T., T. Funai, and A. Ichiyama. 1990. Generation from a single gene of two mRNAs that encode the mitochondrial and peroxisomal serine : pyruvate aminotransferase of rat liver. J. Biol. Chem. 265:75137519.
Oda, T., H. Miyajima, Y. Suzuki, and A. Ichiyama. 1987. Nucleotide sequence of the cDNA encoding the precursor for mitochondrial serine : pyruvate aminotransferase of rat liver. Eur. J. Biochem. 168:537542.[Abstract]
Oda, T., M. Yanagisawa, and A. Ichiyama. 1982. Induction of serine : pyruvate aminotransferase in rat liver organelles by glucagon and a high-protein diet. J. Biochem. (Tokyo) 91:219232.
Page, R. D. 1996. TREEVIEW: an application to display phylogenetic trees on personal computers. Comput. Appl. Biosci. 12:357358.[Medline]
Purdue, P. E., M. J. Lumb, and C. J. Danpure. 1992. Molecular evolution of alanine : glyoxylate aminotransferase 1 intracellular targeting. Analysis of the marmoset and rabbit genes. Eur. J. Biochem. 207:757766.[Abstract]
Purvis, A. 1995. A composite estimate of primate phylogeny. Philos. Trans. R. Soc. Lond. B Biol. Sci. 348:405421.[ISI][Medline]
Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, New York.
Schneider, G., S. Sjoling, E. Wallin, P. Wrede, E. Glaser, and G. von Heijne. 1998. Feature-extraction from endopeptidase cleavage sites in mitochondrial targeting peptides. Proteins 30:4960.
Smith, R. J., and W. L. Jungers. 1997. Body mass in comparative primatology. J. Hum. Evol. 32:523559.[ISI][Medline]
Stein, I., Y. Peleg, S. Even Ram, and O. Pines. 1994. The single translation product of the FUM1 gene (fumarase) is processed in mitochondria before being distributed between the cytosol and mitochondria in Saccharomyces cerevisiae. Mol. Cell. Biol. 14:47704778.[Abstract]
Takada, Y., N. Kaneko, H. Esumi, P. E. Purdue, and C. J. Danpure. 1990. Human peroxisomal L-alanine : glyoxylate aminotransferase. Evolutionary loss of a mitochondrial targeting signal by point mutation of the initiation codon. Biochem. J. 268:517520.[ISI][Medline]
Takada, Y., and T. Noguchi. 1982. Subcellular distribution, and physical and immunological properties of hepatic alanine: glyoxylate aminotransferase isoenzymes in different mammalian species. Comp. Biochem. Physiol. B 72:597604.
Thompson, J. D., D. G. Higgins, and T. J. Gibson. 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22:46734680.[Abstract]
Vacquier, V. D., W. J. Swanson, and Y. H. Lee. 1997. Positive Darwinian selection on two homologous fertilization proteins: what is the selective pressure driving their divergence? J. Mol. Evol. 44(Suppl. 1):S15S22.
von Heijne, G. 1986. Mitochondrial targeting sequences may form amphiphilic helices. EMBO J. 5:13351342.[Abstract]
Yang, Z. 1998. Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol. Biol. Evol. 15:568573.[Abstract]
Yang, Z., S. Kumar, and M. Nei. 1995. A new method of inference of ancestral nucleotide and amino acid sequences. Genetics 141:16411650.