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PubMed2000

Sequence analysis of a new HLA-DR11 allele in a Caucasian Italian family: DRB1*11272.

This communication describes a new DRB1*11 allele identified in a familial group of Caucasian individuals from central Italy. The new sequence has been officially named DRB1*11272 by the World Health Organization (WHO) Nomenclature Committee (February 2000). It encodes an HLA antigen serologically recognized as DR11. The sequence variation of this new allele was localized to codon 77 of exon 2. It differs at position 230 from DRB1*11011 allele (A replacing C), and at position 231 from DRB1*1127 (C replacing T). At the amino acid level, the DRB1*11272 mutation is silent with respect to the DRB*1127 phenotype, coding for a synonymous asparagine.

Alleles↗
PubMed1997

Molecular evolution of the Amy multigenes in the subgenus Sophophora of Drosophila.

Molecular evolution of the Amy multigenes in Drosophila was investigated using PCR amplification. Twenty-five partial Amy sequences from 13 species belonging mainly to the subgenus Sophophora were determine, and a molecular phylogeny of the Amy genes in Drosophila was constructed, together with published Amy sequences. Clustering of species are mostly consistent with the traditional classification and that inferred from other genes. From sequence divergence between PCR products, several species, including D. elegans and D. fuyamai, were suggested to have multiple copies of the Amy genes. The loss of an intron took place at least three times after the Sophophora radiation. In order to investigate the mechanism of sequence evolution, the numbers of amino acid replacement and synonymous substitutions in five lineages were estimated. The heterogeneity in the relative numbers of synonymous and replacement substitutions among the lineages was found. Possible roles of selection in the sequence evolution of the Amy gene are discussed.

Animals↗
PubMed2002

DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency.

Intracellular concentrations of the nucleotide inosine triphosphate (ITP) are regulated by ITP-ase (EC 3.6.1.19), which is encoded by ITPA on chromosome 20p. Subjects with complete deficiency of ITP-ase activity (MIM 147520) have elevated ITP concentrations in erythrocytes, but no obvious clinical abnormalities. Based on biochemical screening, complete ITP-ase deficiency has been postulated to result from homozygosity for a dysfunctional allele, with an estimated frequency of 0.05 in Caucasians. ITP-ase deficiency has not yet been characterized at the molecular genetic level. Sequencing of the genomic DNA from a Caucasian subject with complete ITP-ase deficiency revealed homozygosity for missense mutation 198C>A, which predicted a threonine for proline substitution at codon 32 (P32T), whereas among 125 normal Caucasians, there were no homozygotes for P32T (P = 0.0079). The P32T allele frequency of 0.07 in Caucasians was similar to the estimates derived from earlier biochemical studies. P32T was found to be present at varying frequency in other ethnic groups. Two common synonymous single-nucleotide polymorphisms were also identified. These ITPAmarkers, including P32T, provide tools for further study of association with clinical and biochemical phenotypes.

Adult↗
PubMed2004

A single nucleotide polymorphism map of the mitochondrial genome of the parasitic nematode Cooperia oncophora.

The 13,636 bp mitochondrial (mt) genome sequence of the trichostrongylid nematode Cooperia oncophora was determined. Like the mt genomes of other nematodes it is AT rich (76.75%) and cytidine is the least common nucleoside in the coding strand. There are 2 ribosomal RNA (rrn) genes, 22 transfer RNA (trn) genes and 12 protein coding genes. The relatively short AT-rich region (304 bp) and the lack of a non-coding region between two of the NADH dehydrogenase genes, nad3 and nad5, makes the mt genome of C. oncophora one of the smallest known to date, having only 525 bp of non-coding regions in total. The majority of the C. oncophora protein encoded genes are predicted to end in an abbreviated stop codon like T or TA. In total, 426 single nucleotide polymorphisms (SNP) were mapped on the mt genome of C. oncophora, which is an average of 1 polymorphism per 32 bp. The most common SNPs in the mt genome of C. oncophora were G/A (59.2%) and C/T (28.4%) transitions. Synonymous substitutions (86.4%) were favoured over non-synonymous substitutions. However, the degree of sequence conservation between individual protein genes of different parasitic nematode species did not always correspond to the relative number of non-synonymous SNPs. The mt genome sequence of C. oncophora presents the first mt genome of a member of the Trichostrongyloidea and will be of importance in refining phylogenetic relationships between nematodes. The, still limited, SNP map presented here provides a basis for obtaining insight into the genetic diversity present in the different protein coding genes, trn, rrn and non-coding regions. A more detailed study of the more variable regions will be of use in determining the population genetic structure of C. oncophora. Ultimately this knowledge will add to the understanding of the host-parasite relationship.

Amino Acid Sequence↗
PubMed2006

Identification of physicochemical selective pressure on protein encoding nucleotide sequences.

BACKGROUND: Statistical methods for identifying positively selected sites in protein coding regions are one of the most commonly used tools in evolutionary bioinformatics. However, they have been limited by not taking the physiochemical properties of amino acids into account. RESULTS: We develop a new codon-based likelihood model for detecting site-specific selection pressures acting on specific physicochemical properties. Nonsynonymous substitutions are divided into substitutions that differ with respect to the physicochemical properties of interest, and those that do not. The substitution rates of these two types of changes, relative to the synonymous substitution rate, are then described by two parameters, gamma and omega respectively. The new model allows us to perform likelihood ratio tests for positive selection acting on specific physicochemical properties of interest. The new method is first used to analyze simulated data and is shown to have good power and accuracy in detecting physicochemical selective pressure. We then re-analyze data from the class-I alleles of the human Major Histocompatibility Complex (MHC) and from the abalone sperm lysine. CONCLUSION: Our new method allows a more flexible framework to identify selection pressure on particular physicochemical properties.

Algorithms↗
PubMed1999

Genealogical evidence for positive selection in the nef gene of HIV-1.

The pattern and process of evolution in the nef gene of HIV-1 was analyzed within and among patients. Using a maximum likelihood method that allows for variable intensity of selection pressure among codons, strong positive selection was detected in a hemophiliac patient over 30 mo of infection. By reconstructing the process of allele substitution in this patient using parsimony, the synapomorphic amino acid changes separating each time point were found to have high probabilities of being under positive selection, with selective coefficients of at least 3.6%. Positive selection was also detected among 39 nef sequences from HIV-1 subtype B. In contrast, multiple pairwise comparisons of nonsynonymous and synonymous substitution rates provided no good evidence for positive selection and sliding window analyses failed to detect most positively selected sites. These findings demonstrate that positive selection is an important determinant of nef gene evolution and that genealogy-based methods outperform pairwise methods in the detection of adaptive evolution. Mapping the locations of positively selected sites may also be of use in identifying targets of the immune response and hence aid vaccine design.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Accuracy and power of the likelihood ratio test for comparing evolutionary rates among genes.

Sequences for multiple protein-coding genes are now commonly available from several, often closely related species. These data sets offer intriguing opportunities to test hypotheses regarding whether different types of genes evolve under different selective pressures. Although maximum likelihood (ML) models of codon substitution that are suitable for such analyses have been developed, little is known about the statistical properties of these tests. We use a previously developed fixed-sites model and computer simulations to examine the accuracy and power of the likelihood ratio test (LRT) in comparing the nonsynonymous-to-synonymous substitution rate ratio (omega = dN/dS) between two genes. Our results show that the LRT applied to fixed-sites models may be inaccurate in some cases when setting significance thresholds using a chi(2) approximation. Instead, we use a parametric bootstrap to describe the distribution of the LRT statistic for fixed-sites models and examine the power of the test as a function of sampling variables and properties of the genes under study. We find that the power of the test is high (>80%) even when sampling few taxa (e.g., six species) if sequences are sufficiently diverged and the test is largely unaffected by the tree topology used to simulate data. Our simulations show fixed-sites models are suitable for comparing substitution parameters among genes evolving under even strong evolutionary constraint (omega approximately 0.05), although relative rate differences of 25% or less may be difficult to detect.

Biological Evolution↗
PubMed1996

Numerous transposed sequences of mitochondrial cytochrome oxidase I-II in aphids of the genus Sitobion (Hemiptera: Aphididae).

Polymerase chain reaction (PCR) products corresponding to 803 bp of the cytochrome oxidase subunits I and II region of mitochondrial DNA (mtDNA COI-II) were deduced to consist of multiple haplotypes in three Sitobion species. We investigated the molecular basis of these observations. PCR products were cloned, and six clones from one individual per species were sequenced. In each individual, one sequence was found commonly, but also two or three divergent sequences were seen. The divergent sequences were shown to be nonmitochondrial by sequencing from purified mtDNA and Southern blotting experiments. All seven nonmitochondrial clones sequenced to completion were unique. Nonmitochondrial sequences have a high proportion of unique sites, and very few characters are shared between nonmitochondrial clones to the exclusion of mtDNA. From these data, we infer that fragments of mtDNA have been transposed separately (probably into aphid chromosomes), at a frequency only known to be equalled in humans. The transposition phenomenon appears to occur infrequently or not at all in closely related genera and other aphids investigated. Patterns of nucleotide substitution in mtDNA inferred over a parsimony tree are very different from those in transposed sequences. Compared with mtDNA, nonmitochondrial sequences have less codon position bias, more even exchanges between A, G, C and T, and a higher proportion of nonsynonymous replacements. Although these data are consistent with the transposed sequences being under less constraint than mtDNA, changes in the nonmitochondrial sequences are not random: there remains significant position bias, and probable excesses of synonymous replacements and of conservative inferred amino acid replacements. We conclude that a proportion of the inferred change in the nonmitochondrial sequences occurred before transposition. We believe that Sitobion aphids (and other species exhibiting mtDNA transposition) may be important for studying the molecular evolution of mtDNA and pseudogenes. However, our data highlight the need to establish the true evolutionary relationships between sequences in comparative investigations.

Animals↗
PubMed2003

Low hanging fruit: a subset of human cSNPs is both highly non-uniform and predictable.

We present a point mutation classification method that contrasts SNP databases and has the potential to illuminate the relative mutational load of genes caused by codon bias. We group point variation gleaned from public databases by their wild-type and mutant codons, e.g. codon mutation classes (CMCs, 576 possible such as ACG-->ATG), whose frequencies in a database are assembled into a BLOSUM-style matrix describing the likelihood of observing all possible single base codon changes as tuned by the intertwined effects of mutation rate and selection. The rankings of the CMCs in any database are reshuffled according to the population stratification of the typical genotyping experiment producing that resource's data. Analysis of four independent databases reveals that a considerable fraction of mutation in functional genes can be described by a few CMCs regardless of gene identity or population stratification in the genotyping experiment. For example, the top 5% (29/576) of CMCs account for 27.4% of the observed variants in dbSNP while the bottom 5% account for only 0.02%. For non-synonymous disease-causing mutation, 40.8% are described by the top 5% of all possible non-silent CMCs (22/438). Overall, the most observed polymorphism is a G-->A transition at CpG dinucleotides causing ACG, TCG, GCG, and CCG to frequently undergo silent mutation in any gene due to the putative lack of impact on the protein product. In order to assess how well CMC spectrums estimate the aggregate non-synonymous mutational trends of a single gene, a CMC matrix was applied to seven unrelated genes to compute the most likely point mutations. In excess of 87% of these mutation predictions are historically known to play an important role in a disease state according to published literature. CMC-based mutation prediction may aid design and execution of direct association genotyping studies.

Base Sequence↗
PubMed1998

Sensitivity of patterns of molecular evolution to alterations in methodology: a critique of Hughes and Yeager.

Employing a set of 43 othologous mouse and rat genes, Hughes and Yeager (J. Mol. Evol. 45:125-130, 1997) reported (1) no correlation between synonymous and nonsynonymous rates of nucleotide substitution, (2) a positive correlation between intronic GC contents (GCi) and intronic substitution rates (Ki), (3) that the average Ki value was very similar to the average Ks value, and (4) that the compositional correlation between the rat and the mouse genes is stronger at the third codon position (GC3) than at the first and second codon positions (GC12). We have examined the robustness of these results to alterations in substitution rate estimation protocol, alignment protocol, and statistical procedure. We find that a significant correlation between Ka and Ks is observed either if a rank correlation statistic is used instead of regression analysis, if one outlier is excluded from the analysis, or if a regression weighted by gene size is employed. The correlation between Ki and GCi we find to be sensitive to changes in alignment protocol and disappears on the use of weighted means. The finding that Ks and Ki are approximately the same is dependent on the method for estimating Ks values. Finally, the variance around the regression line of rat GC3 versus mouse GC3 we find to be significantly higher than that in GC12. The source of the discrepancy between this and Hughes and Yeager's result is unclear. The variance around the line for GC4 is higher still, as might be expected. Using a methodology that may be considered preferable to that of Hughes and Yeager, we find that all four of their results are contradicted. More importantly this analysis reinforces the need for caution in assembling and analyzing data sets, as the degree of sensitivity to what many might consider minor methodological alterations is unexpected.

Animals↗
PubMed2003

Abundance of plastid DNA insertions in nuclear genomes of rice and Arabidopsis.

Pairwise comparison of whole plastid and draft nuclear genomic sequences of Arabidopsis thaliana and Oryza sativa L. ssp. indica shows that rice nuclear genomic sequences contain homologs of plastid DNA covering about 94 kb (83%) of plastid genome and including one or more full-length intact (without mutations resulting in premature stop codons) homologues of 26 known protein-coding (KPC) plastid genes. By contrast, only about 20 kb (16%) of chloroplast DNA, including a single intact plastid-derived KPC gene, is presented in the nucleus of A. thaliana. Sixteen rice plastid genes have at least one nuclear copy without any mutation or with only synonymous substitutions. Nuclear copies for other ten plastid genes contain both synonymous and non-synonymous substitutions. Multiple ESTs for 25 out of 26 KPC genes were also found, as well as putative promoters for some of them. The study of substitutions pattern shows that some of nuclear homologues of plastid genes may be functional and/or are under the pressure of the positive natural selection. The similar comparative analysis performed on rice chromosome 1 revealed 27 contigs containing plastid-derived sequences, totalling about 84 kb and covering two thirds of chloroplast DNA, with the intact nuclear copies of 26 different KPC genes. One of these contigs, AP003280, includes almost 57 kb (45%) of chloroplast genome with the intact copies of 22 KPC genes. At the same time, we observed that relative locations of homologues in plastid DNA and the nuclear genome are significantly different.

Arabidopsis↗
PubMed1997

Novel HLA-B35 subtypes: putative gene conversion events with donor sequences from alleles common in native Americans (HLA-B*4002 or B*4801).

In a study of 523 normal subjects of differing ethnic groups, including 189 South American Indians, we have described novel hybridization pattern corresponding to 22 potentially new HLA-B locus alleles. Three of these alleles were subtypes of B35. The locally, assigned alleles, B-3504v, B-3505v, and B-3508v have been sequenced and were officially designated as B*3512, B*3517, and B*3518, respectively. In addition, we determined the nucleotide sequence of another new variant, locally designated B-3509.2. B*3517, was found in 3 individuals (2 Hispanic, 1 Caucasian), it differs from B*3505 by 3 nucleotide substitutions that lead to changes in residues 94, 95, and 103. B*3517 differs from B*3501 in residues 97 and 103. B*3518 was found in 7 South American Indian individuals (6 of 124 Toba Indians, 1 of 18 Pilaga Indians). It differs from B*3509 by 2 silent nucleotide substitutions and by one nonsynonymous substitution in codon 156 (Arg-->Leu). B*3512 differs from B*3504 by 3 nucleotides, one of them leading to a substitution in residue 103 (Val-->Leu). B*3509 was observed in 3 individuals from the Wichi tribe. The nucleotide sequence of one of these was determined and was found to differ from B*35091 by two synonymous nucleotide substitutions. The distinguishing amino acid substitutions in residues 95, 97, and 156 contribute to the structure of specificity pockets F, C, and E, and D and E respectively, therefore, it is possible that some of the new alleles may have different peptide binding profiles. It has been shown that differences at residue 156 may elicit different allorecognition and mediate graft-versus-host disease and rejection in bone marrow transplantation. The mechanisms for the generation of these novel alleles may involve gene conversion events in which short exon-3 segments from the common Native American alleles B*4002 or B*4801 were inserted in HLA-B35 backbone structures. The novel allele B*3518 is closely related to B*35092 and to B*3508. Two alternative hypotheses for its generation can be suggested, the most plausible one would involve B*35092, the putative progenitor of B*3518, since both alleles are prevalent in the same Indian tribes.

Alleles↗
PubMed1998

Diversifying selection governs sequence polymorphism in the major adhesin proteins fimA, papA, and sfaA of Escherichia coli.

Fimbriae or pili are essential adherence factors usually found in pathogenic bacteria to aid colonization of host cells. Three major structural pilin genes, fimA, sfaA, and papA, from Escherichia coli natural isolates were examined and nucleotide sequence data revealed elevated levels of both synonymous and nonsynonymous site variation at these loci. Examination of synonymous site variation shows a fivefold increase in fimA sites, relative to the housekeeping gene mdh; and similarly the sfaA and papA genes have increased synonymous sites variation relative to fimA. Nonsynonymous site variation is also elevated at all three loci but, in particular, at the papA locus (kN = 0.44). The kN/kS ratio for the three genes are among the highest yet reported for E. coli genes. Regional variation in nucleotide polymorphism within each of the genes reveal hypervariable segments where nonsynonymous substitutions exceed synonymous substitutions. We propose that at the fimA, papA, and sfaA genes, diversifying selection has brought about the increase levels of polymorphism.

Adhesins, Escherichia coli↗
PubMed2006

The complete chloroplast genome sequence of Citrus sinensis (L.) Osbeck var 'Ridge Pineapple': organization and phylogenetic relationships to other angiosperms.

BACKGROUND: The production of Citrus, the largest fruit crop of international economic value, has recently been imperiled due to the introduction of the bacterial disease Citrus canker. No significant improvements have been made to combat this disease by plant breeding and nuclear transgenic approaches. Chloroplast genetic engineering has a number of advantages over nuclear transformation; it not only increases transgene expression but also facilitates transgene containment, which is one of the major impediments for development of transgenic trees. We have sequenced the Citrus chloroplast genome to facilitate genetic improvement of this crop and to assess phylogenetic relationships among major lineages of angiosperms. RESULTS: The complete chloroplast genome sequence of Citrus sinensis is 160,129 bp in length, and contains 133 genes (89 protein-coding, 4 rRNAs and 30 distinct tRNAs). Genome organization is very similar to the inferred ancestral angiosperm chloroplast genome. However, in Citrus the infA gene is absent. The inverted repeat region has expanded to duplicate rps19 and the first 84 amino acids of rpl22. The rpl22 gene in the IRb region has a nonsense mutation resulting in 9 stop codons. This was confirmed by PCR amplification and sequencing using primers that flank the IR/LSC boundaries. Repeat analysis identified 29 direct and inverted repeats 30 bp or longer with a sequence identity > or = 90%. Comparison of protein-coding sequences with expressed sequence tags revealed six putative RNA edits, five of which resulted in non-synonymous modifications in petL, psbH, ycf2 and ndhA. Phylogenetic analyses using maximum parsimony (MP) and maximum likelihood (ML) methods of a dataset composed of 61 protein-coding genes for 30 taxa provide strong support for the monophyly of several major clades of angiosperms, including monocots, eudicots, rosids and asterids. The MP and ML trees are incongruent in three areas: the position of Amborella and Nymphaeales, relationship of the magnoliid genus Calycanthus, and the monophyly of the eurosid I clade. Both MP and ML trees provide strong support for the monophyly of eurosids II and for the placement of Citrus (Sapindales) sister to a clade including the Malvales/Brassicales. CONCLUSION: This is the first complete chloroplast genome sequence for a member of the Rutaceae and Sapindales. Expansion of the inverted repeat region to include rps19 and part of rpl22 and presence of two truncated copies of rpl22 is unusual among sequenced chloroplast genomes. Availability of a complete Citrus chloroplast genome sequence provides valuable information on intergenic spacer regions and endogenous regulatory sequences for chloroplast genetic engineering. Phylogenetic analyses resolve relationships among several major clades of angiosperms and provide strong support for the monophyly of the eurosid II clade and the position of the Sapindales sister to the Brassicales/Malvales.

Ananas↗
PubMed1990

A gene for cytochrome c oxidase subunit III (COXIII) in broad bean mitochondrial DNA: structural features and sequence evolution.

A nucleotide sequence of broad bean mitochondrial DNA (mtDNA) that contains the coxIII gene is presented, and compared to corresponding sequences of Oenothera and corn mtDNAs. Upstream from the broad bean coxIII gene are three potential secondary structures: a single stem and loop (hairpin) that is conserved in the Oenothera and corn sequences; a second single stem and loop; and a double stem and loop. The rate of evolution of the coxIII gene has been slower in plants than in mammals. Constraints on the fixation of at least some kinds of mutations in silent (synonymous) third position nucleotides, as well as of mutations that cause amino acid replacements, seem to have contributed to this slower rate.

Amino Acid Sequence↗
PubMed2001

MtDNA mutations in maternally inherited diabetes: presence of the 3397 ND1 mutation previously associated with Alzheimer's and Parkinson's disease.

Mutations in the mitochondrial tRNA(leu) (UUR) gene have been associated with diabetes mellitus and deafness. We screened for the presence of mtDNA mutations in the tRNA(leu) (UUR) gene and adjacent ND1 sequences in 12 diabetes mellitus pedigrees with a possible maternal inheritance of the disease. One patient carried a G to A substitution at nt 3243 (tRNA(leu) (UUR) gene) in heteroplasmic state. In a second pedigree a patient had an A to G substitution at nt 3397 in the ND1 gene. All maternal relatives of the proband had the 3397 substitution in homoplasmic state. This substitution was not present in 246 nonsymptomatic Caucasian controls. The 3397 substitution changes a highly conserved methionine to a valine at aa 31 and has previously been found in Alzheimer's (AD) and Parkinson's (PD) disease patients. Substitutions in the mitochondrial ND1 gene at aa 30 and 31 have associated with a number of different diseases (e.g. AD/PD, MELAS, cardiomyopathy and diabetes mellitus, LHON, Wolfram-syndrome and maternal inherited diabetes) suggesting that changes at these two codons may be associated with very diverse pathogenic processes. In a further attempt to search for mtDNA mutations outside the tRNAleu gene associated with diabetes, the whole mtDNA genome sequence was determined for two patients with maternally inherited diabetes and deafness. Except for substitutions previously reported as polymorphisms, none of the two patients showed any non-synonymous substitutions either in homoplasmic or heteroplasmic state. These results imply that the maternal inherited diabetes and deafness in these patients must result from alterations of nuclear genes and/or environmental factors.

Alzheimer Disease↗
PubMed2005

A Bayesian model comparison approach to inferring positive selection.

A popular approach to detecting positive selection is to estimate the parameters of a probabilistic model of codon evolution and perform inference based on its maximum likelihood parameter values. This approach has been evaluated intensively in a number of simulation studies and found to be robust when the available data set is large. However, uncertainties in the estimated parameter values can lead to errors in the inference, especially when the data set is small or there is insufficient divergence between the sequences. We introduce a Bayesian model comparison approach to infer whether the sequence as a whole contains sites at which the rate of nonsynonymous substitution is greater than the rate of synonymous substitution. We incorporated this probabilistic model comparison into a Bayesian approach to site-specific inference of positive selection. Using simulated sequences, we compared this approach to the commonly used empirical Bayes approach and investigated the effect of tree length on the performance of both methods. We found that the Bayesian approach outperforms the empirical Bayes method when the amount of sequence divergence is small and is less prone to false-positive inference when the sequences are saturated, while the results are indistinguishable for intermediate levels of sequence divergence.

Bayes Theorem↗
PubMed2001

Estimating the influence of selection on the variable amino acid sites of the cytochrome B protein functional domains.

We evaluated the effects of selection on the molecular evolution of the functional domains of the mammalian cytochrome b gene as it relates to physicochemical properties shown to correlate with rates of amino acid replacement. Two groups of mammals were considered: pocket gophers of the rodent family Geomyidae, and cetaceans and ungulates of the monophyletic taxon Cetartopdactyla. Several characteristics of cytochrome b evolution were common to both mammal groups. The evolution of the matrix domain reflected the region's relative lack of function. Goodness of fit to neutral expectations indicated that external influences have had very little effect on the evolution of the matrix, although in some cases conservative and moderate changes have been favored. Although rates of synonymous nucleotide substitution have been relatively high, the transmembrane domain exhibited poor goodness of fit to neutral expectations. However, the evolution of the transmembrane domain has been constrained by negative selection, allowing a preponderance of conservative and moderate amino acid replacements. We hypothesize that a high rate of substitution is maintained in spite of negative selection because the codons of the transmembrane coding region are predisposed to conservative changes in all amino acid properties. The evolutionary patterns of the intermembrane domain in pocket gophers and cetartiodactyls, however, were very different. Changes inferred from the pocket gopher phylogenetic tree exhibited a significant fit to neutral expectations for each of the amino acid properties. Changes inferred from the cetartiodactyl tree exhibited significant fit to neutral expectations for polarity and isoelectric point, but not for composition, molecular volume, polar requirement, or hydropathy. In each case, lack of fit was due to selection that promoted conservative or moderate change, with the noteworthy exception of polar requirement. We detected an unexpectedly large change in polar requirement (from aspartic acid to threonine) in two separate lineages (Camelus bactrianus and all cetaceans) at amino acid position 159. This inferred change occurred in a region of the cyt-b protein that directly interacts with external surface proteins of the cytochrome bc(1) complex and resulted in a reversion to a more common character state in vertebrates.

Amino Acids↗