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C F Aquadro

Publications and source records attributed to C F Aquadro.

At least 73 records · Page 4Linked to original sources

Rapid antigenic-type replacement and DNA sequence evolution of canine parvovirus.

Analysis of canine parvovirus (CPV) isolates with a panel of monoclonal antibodies showed that after 1986, most viruses isolated from dogs in many parts of the United States differed antigenically from the viruses isolated prior to that date. The new antigenic type (designated CPV type 2b) has largely replaced the previous antigenic type (CPV type 2a) among virus isolates from the United States. This represents the second occurrence of a new antigenic type of this DNA virus since its emergence in 1978, as the original CPV type (CPV type 2) had previously been replaced between 1979 and 1981 by the CPV type 2a strain. DNA sequence comparisons showed that CPV types 2b and 2a differed by as few as two nonsynonymous (amino acid-changing) nucleotide substitutions in the VP-1 and VP-2 capsid protein genes. One mutation, resulting in an Asn-Asp difference at residue 426 in the VP-2 sequence, was shown by comparison with a neutralization-escape mutant selected with a non-CPV type 2b-reactive monoclonal antibody to determine the antigenic change. The mutation selected by that monoclonal antibody, a His-Tyr difference in VP-2 amino acid 222, was immediately adjacent to residue 426 in the three-dimensional structure of the CPV capsid. The CPV type 2b isolates are phylogenetically closely related to the CPV type 2a isolates and are probably derived from a common ancestor. Phylogenetic analysis showed a progressive evolution away from the original CPV type. This pattern of viral evolution appears most similar to that seen in some influenza A viruses.

Amino Acid Sequence↗

DNA "fingerprinting" reveals high levels of inbreeding in colonies of the eusocial naked mole-rat.

Using the technique of DNA fingerprinting, we investigated the genetic structure within and among four wild-caught colonies (n = 50 individuals) of a eusocial mammal, the naked mole-rat (Heterocephalus glaber; Rodentia: Bathyergidae). We found that DNA fingerprints of colony-mates were strikingly similar and that between colonies they were much more alike than fingerprints of non-kin in other free-living vertebrates. Extreme genetic similarity within colonies is due to close genetic relationship (mean relatedness estimate +/- SE, r = 0.81 +/- 0.10), which apparently results from consanguineous mating. The inbreeding coefficient (F = 0.45 +/- 0.18) is the highest yet recorded among wild mammals. The genetic structure of naked mole-rat colonies lends support to kin selection and ecological constraints models for the evolution of cooperative breeding and eusociality.

Animals↗

DNA sequence evolution of the amylase multigene family in Drosophila pseudoobscura.

The alpha-Amylase locus in Drosophila pseudoobscura is a multigene family of one, two or three copies on the third chromosome. The nucleotide sequences of the three Amylase genes from a single chromosome of D. pseudoobscura are presented. The three Amylase genes differ at about 0.5% of their nucleotides. Each gene has a putative intron of 71 (Amy1) or 81 (Amy2 and Amy3) bp. In contrast, Drosophila melanogaster Amylase genes do not have an intron. The functional Amy1 gene of D. pseudoobscura differs from the Amy-p1 gene of D. melanogaster at an estimated 13.3% of the 1482 nucleotides in the coding region. The estimated rate of synonymous substitutions is 0.398 +/- 0.043, and the estimated rate of nonsynonymous substitutions is 0.068 +/- 0.008. From the sequence data we infer that Amy2 and Amy3 are more closely related to each other than either is to Amy1. From the pattern of nucleotide substitutions we reason that there is selection against synonymous substitutions within the Amy1 sequence; that there is selection against nonsynonymous substitutions within the Amy2 sequence, or that Amy2 has recently undergone a gene conversion with Amy1; and that Amy3 is nonfunctional and subject to random genetic drift.

Amylases↗

Increased variation in ADH enzyme activity in Drosophila mutation-accumulation experiment is not due to transposable elements at the Adh structural gene.

We present here a molecular analysis of the region surrounding the structural gene encoding alcohol dehydrogenase (Adh) in 47 lines of Drosophila melanogaster that have each accumulated mutations for 300 generations. While these lines show a significant increase in variation of alcohol dehydrogenase enzyme activity compared to control lines, we found no restriction map variation in a 13-kb region including the complete Adh structural gene and roughly 5 kb of both 5' and 3' sequences. Thus, the rapid accumulation of ADH activity variation after 28,200 allele generations does not appear to have been due to the mobilization of transposable elements into or out of the Adh structural gene region.

Alcohol Dehydrogenase↗

Restriction map and alpha-amylase activity variation among Drosophila mutation accumulation lines.

The specific activities of alpha-amylase were measured for two sets of mutation accumulation lines, each set having originated from a different lethal-carrying second chromosome and SM1(Cy) chromosome and having been maintained by a balanced lethal system for about 300 generations. Significant variation was found to have accumulated among lines of both sets. Because of dysgenic crosses in the early generations of mutation accumulation, insertions or deletions of transposable elements in the Amy gene region were suspected of being the cause of this variation. In order to test this possibility, the structural changes in the 14 kb region of these chromosomes that includes the structural genes for alpha-amylase were investigated by restriction map analysis. We found that most part of the activity variation is due to replacements of a chromosomal region of SM1(Cy), including the structural genes for alpha-amylase, by the corresponding regions of the lethal chromosomes. One line also contained an insertion in this region but this line has an intermediate activity value. Thus, insertions of transposable elements into the Amy gene region were not found to be responsible for the new variation observed in alpha-amylase activity. If we remove those lines with structural changes from the analysis, the genetic variance of alpha-amylase specific activity among lines becomes non-significant in both sets of chromosomes.

Animals↗

Mitochondrial DNA in the bark weevils: size, structure and heteroplasmy.

Mitochondrial DNA of higher animals has been described as an example of extreme efficiency in genome structure and function. Where exceptionally large size molecules have been found (greater than 20 kb), most have occurred as rare variants within a species, suggesting that these variants arise infrequently and do not persist for long periods in evolutionary time. In contrast, all individuals of at least three species of bark weevil (Curculionidae: Pissodes) possess a mitochondrial genome of unusually large size (30-36 kb). The molecule owes its large size to a dramatically enlarged A + T-rich region (9-13 kb). Gene content and order outside of this region appear to be identical to that found in Drosophila. A series of 0.8-2.0-kb repeated sequences occur adjacent to the large A + T rich region and have perhaps played a role in the generation of the large size as well as an unprecedented frequency of size variant heteroplasmy. Every weevil sampled in all three species (n = 219) exhibits anywhere from two to five distinct size classes of mtDNA. The persistence of this large amount of size polymorphism through two speciation events combined with the abundant size variation within individuals suggests that these molecules may not be subject to strong selection for small overall size and efficiency of replication. This pattern of variation contrasts strongly with the conservation of gene content and arrangement in the coding region of the molecule.

Animals↗

Canine host range and a specific epitope map along with variant sequences in the capsid protein gene of canine parvovirus and related feline, mink, and raccoon parvoviruses.

Canine parvovirus (CPV) is a recently recognized pathogen of dogs that is similar to the long-recognized feline, mink, and raccoon parvoviruses. Relationships between the viruses determined from DNA sequences of the capsid protein genes of 10 virus isolates showed the CPV isolates to be closely related to the other viruses, although comprising a distinct group. No immediate ancestor of CPV was observed amongst the mink, cat, or raccoon viruses examined. Three different directly repeated sequences were present within the noncoding region downstream from the capsid protein genes. Analysis of recombinants between CPV and feline panleukopenia virus at restriction sites within the capsid protein genes mapped a CPV-specific neutralization epitope on the virus capsid, differences in the pH dependence of hemagglutination, and part of the determinant of canine host range between 59 and 64 genome map units (m.u.). Those differences were therefore the result of up to three nucleotide or predicted amino acid sequence differences in that region. A second region between 64 and 73 m.u., which may affect the viability of certain recombinant viruses, contained four nucleotide differences, one of which was a coding change.

Animals↗

The rosy region of Drosophila melanogaster and Drosophila simulans. I. Contrasting levels of naturally occurring DNA restriction map variation and divergence.

A 40-kb region around the rosy and snake loci was analyzed for restriction map variation among 60 lines of Drosophila melanogaster and 30 lines of Drosophila simulans collected together at a single locality in Raleigh, North Carolina. DNA sequence variation in D. simulans was estimated to be 6.3 times greater than in D. melanogaster (heterozygosities per nucleotide of 1.9% vs. 0.3%). This result stands in marked contrast to results of studies of phenotypic variation including proteins (allozymes), morphology and chromosome arrangements which are generally less variable and less geographically differentiated in D. simulans. Intraspecific polymorphism is not distributed uniformly over the 40-kb region. The level of heterozygosity per nucleotide varies more than 12-fold across the region in D. simulans, being highest over the hsc2 gene. Similar, though less extreme, variation in heterozygosity is also observed in D. melanogaster. Average interspecific divergence (corrected for intraspecific polymorphism) averaged 3.8%. The pattern of interspecific divergence over the 40-kb region shows some disparities with the spatial distribution of intraspecific variation, but is generally consistent with selective neutrality predictions: the most polymorphic regions within species are generally the most divergent between species. Sequence-length polymorphism is observed for D. melanogaster to be at levels comparable to other gene regions in this species. In contrast, no sequence length variation was observed among D. simulans chromosomes (limit of resolution approximately 100 bp). These data indicate that transposable elements play at best a minor role in the generation of naturally occurring genetic variation in D. simulans compared to D. melanogaster. We hypothesize that differences in species effective population size are the major determinant of the contrasting levels and patterns of DNA sequence and insertion/deletion variation that we report here and the patterns of allozyme and morphological variation and differentiation reported by other workers for these two species.

Animals↗

Restriction-map variation in the Notch region of Drosophila melanogaster.

A worldwide sample of 37 X chromosomes of Drosophila melanogaster was analyzed with four restriction endonucleases for a 60-kb region of the Notch locus. Any two randomly chosen homologous chromosomes were heterozygous at one in 143 nucleotides (theta = 0.007). The chromosomes that were sampled contained no more than one insertion/deletion. The four insertions and one deletion observed in the 37 chromosomes sampled were located 3' to the Notch transcript; one insertion was represented twice in the sample. The amount of linkage disequilibrium in the Notch region appears to be lower than that of the alcohol dehydrogenase locus in D. melanogaster. The few instances of linkage disequilibrium observed could be due to geographic differentiation of African populations. The genetic variation estimates in the Notch region were comparable with those of the alcohol dehydrogenase region in D. melanogaster, suggesting that molecular genetic variation on the X chromosome is not dramatically reduced by selection against slightly deleterious alleles.

Animals↗

Nucleotide sequence of the Adh gene region of Drosophila pseudoobscura: evolutionary change and evidence for an ancient gene duplication.

The alcohol dehydrogenase (Adh) locus (ADH; alcohol: NAD+ oxidoreductase, EC 1.1.1.1) of Drosophila pseudoobscura was cloned and sequenced. Forty-five percent of the "effectively silent sites" have changed between Adh in D. pseudoobscura of the obscura species group and the homologous DNA sequence in D. mauritiana, the latter representing the melanogaster species group. The untranslated leader sequence of the adult transcript of D. pseudoobscura has two deletions relative to the D. mauritiana message. The ADH protein sequences of D. pseudoobscura is missing the third and fourth amino acids at the N-terminus relative to the D. mauritiana enzyme. Of the remaining 254 amino acid positions, 27 (10.64%) differ between the two species. Amino acid replacements are randomly distributed into hydrophilic and hydrophobic domains of ADH. However, replacement substitutions are distributed nonrandomly across the three exons among D. pseudoobscura and members of the melanogaster subgroup, suggesting that functional constraints across the exons are different. Surprisingly, silent substitutions are also nonrandomly distributed with the third exon being the most divergent. This pattern suggests possible selective constraints on supposedly neutral silent substitutions and/or variation in underlying mutation rates across the gene. The presence of transcriptional and translational signals at the beginning and end of conserved sequences 3' to Adh implies the existence of a previously undescribed gene. Codon usage and patterns of nucleotide divergence are consistent with a protein coding function for this gene. In addition, conservation of nucleotide and amino acid sequence and similarity in hydropathy plots suggests that the gene 3' to Adh represents an ancient duplication of the Adh gene.

Alcohol Dehydrogenase↗

Restriction-map variation in the alcohol dehydrogenase region of Drosophila pseudoobscura.

A 32-kb region including the Adh structural gene was analyzed with six restriction endonucleases in 20 lines of Drosophila pseudoobscura, one line of D. persimilis, and one line of D. miranda. Nineteen lines of D. pseudoobscura from a single population were estimated to be polymorphic at one in every 15 nucleotides (p = 0.066). Any two homologous chromosomes chosen at random were heterozygous at one in 48 (H = 0.021) nucleotides. Two small insertions of 50 and 200 bp were found approximately 7 kb upstream from the Adh transcript. High haplotype diversity and low linkage disequilibrium suggest that the polymorphic restriction sites around Adh have segregated almost randomly during the history of this D. pseudoobscura population and that the effects of inbreeding and periodic reduction of population size have been negligible. The restriction-endonuclease analysis for the Adh region of D. pseudoobscura stands in sharp contrast to the strong linkage disequilibrium, high levels of insertion/deletion polymorphism, and lower estimates of nucleotide polymorphism found for this same region in D. melanogaster. A phylogeny for the Adh haplotypes is consistent with an early divergence of D. miranda, while D. persimilis falls within the cluster of D. pseudoobscura haplotypes.

Alcohol Dehydrogenase↗

Restriction-map variation in natural populations of Drosophila melanogaster: white-locus region.

Restriction-map variation among 38 chromosomes collected from natural populations from around the world was surveyed using probes for a 45-kb region containing and surrounding the white locus. Insertion and deletion variation was more common in the regions flanking the white transcriptional unit, and restriction-site polymorphism appears to be most common 5' of the white locus. The frequencies of individual large insertions (suspected transposable elements) were low, although 37% of the chromosomes had at least one insertion in the white-locus region. The estimated level of nucleotide heterozygosity over the whole region was 0.012. There was little linkage disequilibrium among the polymorphic sites. In contrast to earlier reports of the variation in other regions of the Drosophila melanogaster genome, there seemed to be less linkage disequilibrium and perhaps more nucleotide polymorphism.

Animals↗

Sequence evolution within populations under multiple types of mutation.

DNA sequence and restriction map data from natural populations can be used to estimate the phylogenetic history of observed sequences. Studies of this sort usually examine large regions of DNA where many evolutionary events have taken place. From such data, detailed phylogenies can be constructed and qualitatively different kinds of mutational and substitutional processes can be studied. The value of investigating more than one mutational type is in the power of comparing relative rates of these distinct substitutional processes. In this paper, we construct a neutral model to describe the frequencies of sequence haplotypes according to the haplotypes from which they arose. This theory of the frequency of haplotypes (incorporating their historical past) is applied to data from the alcohol dehydrogenase gene region of Drosophila melanogaster. The observed patterns of change associated with transposable elements around the Adh locus are not in accord with a neutral model. Values for the mutation rates cannot be found that will bring the observed data into agreement with a simple neutral model, but with the addition of mildly deleterious selection, the model can explain these patterns of change. These results suggest that transposable elements are deleterious to the organisms carrying them, but at levels only several times their rate of transpositional insertion. Similar analyses of small deletions in the Adh region suggest that they may experience mildly deleterious selection.

Animals↗

Molecular population genetics of the alcohol dehydrogenase gene region of Drosophila melanogaster.

Variation in the DNA restriction map of a 13-kb region of chromosome II including the alcohol dehydrogenase structural gene (Adh) was examined in Drosophila melanogaster from natural populations. Detailed analysis of 48 D. melanogaster lines representing four eastern United States populations revealed extensive DNA sequence variation due to base substitutions, insertions and deletions. Cloning of this region from several lines allowed characterization of length variation as due to unique sequence insertions or deletions [nine sizes; 21-200 base pairs (bp)] or transposable element insertions (several sizes, 340 bp to 10.2 kb, representing four different elements). Despite this extensive variation in sequences flanking the Adh gene, only one length polymorphism is clearly associated with altered Adh expression (a copia element approximately 250 bp 5' to the distal transcript start site). Nonetheless, the frequency spectra of transposable elements within and between Drosophila species suggests they are slightly deleterious. Strong nonrandom associations are observed among Adh region sequence variants, ADH allozyme (Fast vs. Slow), ADH enzyme activity and the chromosome inversion ln(2L)t. Phylogenetic analysis of restriction map haplotypes suggest that the major twofold component of ADH activity variation (high vs. low, typical of Fast and Slow allozymes, respectively) is due to sequence variation tightly linked to and possibly distinct from that underlying the allozyme difference. The patterns of nucleotide and haplotype variation for Fast and Slow allozyme lines are consistent with the recent increase in frequency and spread of the Fast haplotype associated with high ADH activity. These data emphasize the important role of evolutionary history and strong nonrandom associations among tightly linked sequence variation as determinants of the patterns of variation observed in natural populations.

Alcohol Dehydrogenase↗

An analysis of the dynamics of mammalian mitochondrial DNA sequence evolution.

The dynamics of the substitution process for mammalian mitochondrial DNA have been modeled. The temporal behavior of several quantities has been studied and the model's predictions have been compared with estimates obtained from recent mtDNA sequence data for an increasingly divergent series of primates, the mouse and the cow (Anderson et al. 1981, 1982; Bibb et al. 1981; Brown et al. 1982). The results are consistent with the hypothesis that the decrease in the proportion of transitions observed as divergence increases is a consequence of the highly biased substitution process. In addition, the results support the hypothesis that, although a portion of the mtDNA molecule evolves at an extremely rapid rate, a significant portion of the molecule is under strong selective constraints.

Animals↗

Human mitochondrial DNA variation and evolution: analysis of nucleotide sequences from seven individuals.

We have analyzed nucleotide sequence variation in an approximately 900-base pair region of the human mitochondrial DNA molecule encompassing the heavy strand origin of replication and the D-loop. Our analysis has focused on nucleotide sequences available from seven humans. Average nucleotide diversity among the sequences is 1.7%, several-fold higher than estimates from restriction endonuclease site variation in mtDNA from these individuals and previously reported for other humans. This disparity is consistent with the rapidly evolving nature of this noncoding region. However, several instances of convergent or parallel gain and loss of restriction sites due to multiple substitutions were observed. In addition, other results suggest that restriction site (as well as pairwise sequence) comparisons may underestimate the total number of substitutions that have occurred since the divergence of two mtDNA sequences from a common ancestral sequence, even at low levels of divergence. This emphasizes the importance of recognizing the large standard errors associated with estimates of sequence variability, particularly when constructing phylogenies among closely related sequences. Analysis of the observed number and direction of substitutions revealed several significant biases, most notably a strand dependence of substitution type and a 32-fold bias favoring transitions over transversions. The results also revealed a significantly nonrandom distribution of nucleotide substitutions and sequence length variation. Significantly more multiple substitutions were observed than expected for these closely related sequences under the assumption of uniform rates of substitution. The bias for transitions has resulted in predominantly convergent or parallel changes among the observed multiple substitutions. There is no convincing evidence that recombination has contributed to the mtDNA sequence diversity we have observed.

Base Sequence↗

Mitochondrial DNA differentiation during the speciation process in Peromyscus.

We address the problem of the possible significance of biological speciation to the magnitude and pattern of divergence of asexually transmitted characters in bisexual species. The empirical data for this report consist of restriction endonuclease site variability in maternally transmitted mitochondrial DNA (mtDNA) isolated from 82 samples of Peromyscus polionotus and P. leucopus collected from major portions of the respective species' ranges. Data are analyzed together with previously published information on P. maniculatus, a sibling species to polionotus. Maps of restriction sites indicate that all of the variation observed can be reasonably attributed to base substitutions leading to loss or gain of particular recognition sites. Magnitude of mtDNA sequence divergence within polionotus (maximum approximately equal to 2%) is roughly comparable to that observed within any of five previously identified mtDNA assemblages in maniculatus. Sequence divergence within leucopus (maximum approximately equal to 4%) is somewhat greater than that within polionotus. Consideration of probable evolutionary links among mtDNA restriction site maps allowed estimation of matriarchal phylogenies within polionotus and leucopus. Clustering algorithms and qualitative Wagner procedures were used to generate phenograms and parsimony networks, respectively, for the between-species comparisons. Three simple graphical models are presented to illustrate some conceivable relationships of mtDNA differentiation to speciation. In theoretical case I, each of two reproductively defined species (A and B) is monophyletic in matriarchal genealogy; the common female ancestor of either species can either predate or postdate the speciation. In case II, neither species is monophyletic in matriarchal genotype. In case III, species B is monophyletic but forms a subclade within A which is thus paraphyletic with respect to B. The empirical results for mtDNA in maniculatus and polionotus appear to conform closely to case III. These theoretical and empirical considerations raise a number of questions about the general relationship of the speciation process to the evolution of uniparentally transmitted traits. Some of these considerations are presented, and it is suggested that the distribution patterns of mtDNA sequence variation within and among extant species should be of considerable relevance to the particular demographies of speciation.

Animals↗