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W M Fitch

Publications and source records attributed to W M Fitch.

At least 19 recordsLinked to original sources

Myc and Max: molecular evolution of a family of proto-oncogene products and their dimerization partner.

The myc gene family encodes a group of transcription factors that regulate cell proliferation and differentiation. These genes are widely studied because of their importance as proto-oncogenes. Phylogenetic analyses are described here for 45 Myc protein sequences representing c-, N-, L-, S-, and B-myc genes. A gene duplication early in vertebrate evolution produced the c-myc lineage and another lineage that later gave rise to the N- and L-myc lineages by another gene duplication. Evolutionary divergence in the myc gene family corresponds closely to the known branching order of the major vertebrate groups. The patterns of sequence evolution are described for five separate highly conserved regions, and these analyses show that differential rates of sequence divergence (= mosaic evolution) have occurred among conserved motifs. Further, the closely related dimerization partner protein Max exhibits significantly less sequence variability than Myc. It is suggested that the reduced variability in max stems from natural selection acting to preserve dimerization capability with products of myc and related genes.

Amino Acid Sequence

European swine virus as a possible source for the next influenza pandemic?

According to phylogenetic data, about 100 years ago an avian influenza virus passed the species barrier (possibly first) to pigs and (possibly from there) to humans. In 1979 an avian influenza A virus (as a whole, without reassortment) again entered the pig population in northern Europe, forming a stable lineage. Here it is shown that the early North European swine viruses exhibit higher than normal evolutionary rates and are highly variable with respect to plaque morphology and neutralizability by monoclonal antibodies. Our results are consistent with the idea that, in order to pass the species barrier, an influenza A virus needs a mutator mutation to provide an additional number of variants, from which the new host might select the best fitting ones. A mutator mutation could be of advantage under such stress conditions and might enable a virus to pass the species barrier as a whole even twice, as it seems to have happened about 100 years ago. This stressful situation should be over for the recent swine lineage, since the viruses seem to be adapted already to the new host in that the most recent isolates--at least in northern Germany--are genetically stable and seem to have lost the putative mutator mutation again.

Animals

Dynamics of IS-related genetic rearrangements in resting Escherichia coli K-12.

An analysis of restriction fragment length polymorphism (RFLP) using eight residential insertion sequence (IS) elements as hybridization probes reveals that the genome of resting bacteria is more dynamic than it was long believed. Escherichia coli strains stored in agar stabs for up to 30 yr accumulate a genetic variation which is correlated to time of storage. This spontaneous mutagenesis is often IS-specific, with particularly high activity for IS5, and thus suggests that transpositional DNA rearrangements are a major cause for the observed genetic polymorphism. The RFLP patterns indicate a burst of IS30 transposition to occur occasionally. Mutation rate is estimated by two different methods to roughly 10(-5) IS-related DNA rearrangements per bacterial chromosome per hour of storage for the eight IS elements studied. A pedigree derived from the RFLP data reveals that populations had evolved independently in each stab and showed no signs of convergence. Relics of an assumed ancestral population were still present in the stab cultures, but the elder stabs provided mostly mutants. These results indicate that cells placed under nutritional deprivation might have a highly plastic genome and suggest that such plasticity might play an adaptive role.

DNA Probes

Testing the covarion hypothesis of molecular evolution.

The covarion hypothesis of molecular evolution states that the fixation of mutations may alter the probability that any given position will fix the next change. Tests of this hypothesis using the divergence of real sequences are compromised because models of rate variation among sites (e.g., the gamma version of the one-parameter equation) predict sequence divergence values similar to those for the covarion process. This study therefore focuses on the extent to which the varied and unvaried codons of two well-diverged taxa are the same, because fewer are expected by the covarion hypothesis than by the gamma model. The data for these tests are the protein sequences of Cu, Zn superoxide dismutase (SOD) for mammals and plants. Simulation analyses show that the covarion hypothesis makes better predictions about the frequencies of varied and unhit positions in common between these two taxa than does the gamma version of the one-parameter model. Furthermore, the analysis of SOD tertiary structure demonstrates that mammal and plant variabilities are distributed differently on the protein. These results support the conclusions that the variable and invariable codons of mammal and plant SODs are different and that the covarion model explains the evolution of this protein better than the gamma version of the one-parameter process. Unlike other models, the covarion hypothesis accounts for rate fluctuations among positions over time, which is an important parameter of molecular evolution.

Animals

Molecular evolution of the MyoD family of transcription factors.

Myogenesis in skeletal muscle is a cascade of developmental events whose initiation involves the MyoD family of transcription factors. Evolutionary analyses of amino acid sequences of this family of transcriptional activators suggest that the vertebrate genes MyoD1, myf-5, Myog (myogenin), and myf-6 were derived by gene duplications from a single ancestral gene. A common genetic origin predicts some functional redundancy between MyoD1 and myf-5 and between Myog and myf-6. Experimental studies have suggested that these pairs of genes can substitute for each other during myogenesis. Separate analyses of the conserved basic helix-loop-helix and nonconserved flanking elements yield similar branching sequences but show evolutionary change in the basic helix-loop-helix region has occurred at a much slower rate.

Animals

Evolutionary relationships of lactate dehydrogenases (LDHs) from mammals, birds, an amphibian, fish, barley, and bacteria: LDH cDNA sequences from Xenopus, pig, and rat.

The nucleotide sequences of the cDNAs encoding LDH (EC 1.1.1.27) subunits LDH-A (muscle), LDH-B (liver), and LDH-C (oocyte) from Xenopus laevis, LDH-A (muscle) and LDH-B (heart) from pig, and LDH-B (heart) and LDH-C (testis) from rat were determined. These seven newly deduced amino acid sequences and 22 other published LDH sequences, and three unpublished fish LDH-A sequences kindly provided by G. N. Somero and D. A. Powers, were used to construct the most parsimonious phylogenetic tree of these 32 LDH subunits from mammals, birds, an amphibian, fish, barley, and bacteria. There have been at least six LDH gene duplications among the vertebrates. The Xenopus LDH-A, LDH-B, and LDH-C subunits are most closely related to each other and then are more closely related to vertebrate LDH-B than LDH-A. Three fish LDH-As, as well as a single LDH of lamprey, also seem to be more related to vertebrate LDH-B than to land vertebrate LDH-A. The mammalian LDH-C (testis) subunit appears to have diverged very early, prior to the divergence of vertebrate LDH-A and LDH-B subunits, as reported previously.

Amino Acid Sequence

The superoxide dismutase molecular clock revisited.

The Cu,Zn superoxide dismutase (SOD) was examined earlier and found to behave in a very unclock-like manner despite (accepted point mutation, or PAM) corrections for multiple replacements per site. Depending upon the time span involved, rates could differ 5-fold. We have sought to determine whether the data might be clock-like if a covarion model were used. We first determined that the number of concomitantly variable codons (covarions) in SOD is 28. With that value fixed we found that the observations for SOD could fit reasonably well a molecular clock if, given 28 covarions, (i) there are approximately six replacements every 10 million years, (ii) the total number of codons is 162, (iii) the number of codons that are permanently invariable across the range of taxa from fungi to mammals is 44, and (iv) the persistence of variability is quite low (0.01). Thus, the inconsistent number of amino acid differences between various pairs of descendent sequences could well be the result of a fairly accurate molecular clock. The general conclusion has two sides: (i) the inference that a given gene is a bad clock may sometimes arise through a failure to take all the relevant biology into account and (ii) one should examine the possibility that different subsets of amino acids are evolving at different rates, because otherwise the assumption of a clock may yield erroneous estimates of divergence times on the basis of the observed number of amino acid differences.

Animals

Insertion sequence-related genetic variation in resting Escherichia coli K-12.

Bacterial subclones recovered from an old stab culture of Escherichia coli K-12 revealed a high degree of genetic diversity, which occurred in spite of a very reduced rate of propagation during storage. This conclusion is based on a pronounced restriction fragment length polymorphism (RFLP) detected upon hybridization with internal fragments of eight resident insertion sequences (IS). Genetic diversity was dependent on the IS considered and, in many cases, a clear consequence of IS transposition. IS5 was particularly active in the generation of variation. All subclones in which IS30 had been active testify to a burst of IS30 transposition. This was correlated with a loss of prototrophy and a reduced growth on rich media. A pedigree of the entire clone could be drawn from the RFLP patterns of the subclones. Out of 118 subclones analyzed, 68 different patterns were found but the putative ancestral population had disappeared. A few patterns were each represented by several subclones displaying improved fitness. These results offer insights into the role of IS elements in the plasticity of the E. coli genome, and they further document that enzyme-mediated DNA rearrangements do occur in resting bacterial cultures.

Biological Evolution

Comparative analysis of multiple protein-sequence alignment methods.

We have analyzed a total of 12 different global and local multiple protein-sequence alignment methods. The purpose of this study is to evaluate each method's ability to correctly identify the ordered series of motifs found among all members of a given protein family. Four phylogenetically distributed sets of sequences from the hemoglobin, kinase, aspartic acid protease, and ribonuclease H protein families were used to test the methods. The performance of all 12 methods was affected by (1) the number of sequences in the test sets, (2) the degree of similarity among the sequences, and (3) the number of indels required to produce a multiple alignment. Global methods generally performed better than local methods in the detection of motif patterns.

Amino Acid Sequence

Phylogenetic inference under the pure drift model.

When pairwise genetic distances are used for phylogenetic reconstruction, it is usually assumed that the genetic distance between two taxa contains information about the time after the two taxa diverged. As a result, upon an appropriate transformation if necessary, the distance usually can be fitted to a linear model such that it is expressed as the sum of lengths of all branches that connect the two taxa in a given phylogeny. This kind of distance is referred to as "additive distance." For a phylogenetic tree exclusively driven by random genetic drift, genetic distances related to coancestry coefficients (theta XY) between any two taxa are more suitable. However, these distances are fundamentally different from the additive distance in that coancestry does not contain any information about the time after two taxa split from a common ancestral population; instead, it reflects the time before the two taxa diverged. In other words, the magnitude of theta XY provides information about how long the two taxa share the same evolutionary pathways. The fundamental difference between the two kinds of distances has led to a different algorithm of evaluating phylogenetic trees when theta XY and related distance measures are used. Here we present the new algorithm using the ordinary-least-squares approach but fitting to a different linear model. This treatment allows genetic variation within a taxon to be included in the model. Monte Carlo simulation for a rooted phylogeny of four taxa has verified the efficacy and consistency of the new method. Application of the method to human population was demonstrated.

Animals

Punctuated equilibrium and positive Darwinian evolution in vesicular stomatitis virus.

RNA viruses possess the potential for rapid evolution and serve as excellent models to test evolutionary theory. Molecular phylogenetic analysis of the P gene for a larger number of diverse natural isolates of vesicular stomatitis virus reveals no evidence for a molecular clock but instead shows a stepwise evolutionary pattern unlike that ever seen before. Each step out from the tree's ancestral root to terminal branch tips correlates not with time of virus isolation but with a south-to-north geographical progression from Panama to the United States. The grossly unequal rates of change within this single species imply an underlying mechanism at odds with the prevailing notion that neutral changes are the dominating feature of molecular evolution. This is also a demonstration of punctuated equilibrium at the molecular level.

Base Sequence

Genetic relatedness of the nucleoprotein (NP) of recent swine, turkey, and human influenza A virus (H1N1) isolates.

The sequences of nucleoprotein (NP) genes of recent human and turkey isolates of influenza A viruses, which serologically could be correlated to contemporary swine viruses, were determined. These sequences were closely related to the NPs of these swine viruses and they formed a separate branch on the phylogenetic tree. While the early swine virus from 1931 resembled the avian strains in consensus amino acids of the NP and in its ability to rescue NP ts mutants of fowl plague virus in chicken embryo cells, the later strains on that branch were different: at 15 positions they have their own amino acids and they rescued the NP ts mutants only poorly. Of the NPs of the human New Jersey/76 isolates analysed, one clustered with the recent H1N1 swine viruses of the U.S.A., the other one with contemporary human strains. Since the NP is one of the main determinants of species specificity it is concluded that, although the H1N1 swine isolates from the U.S.A. form their own branch in the phylogenetic tree, they can be transmitted to humans and turkeys, but they do not spread further in these populations and so far have not contributed to human pandemics. It is not very likely that they will do so in future, since its branch in the phylogenetic tree develops further away from the human and avian branch.

Animals

Exon-specific gene correction (conversion) during short evolutionary periods: homogenization in a two-gene family encoding the beta-chain constant region of the T-lymphocyte antigen receptor.

The two genes encoding the beta-chain constant region of the T-lymphocyte antigen receptor appear to have undergone gene conversion in a number of species, including wild and laboratory mice. To examine the frequency of such events during short evolutionary periods, we have characterized the corresponding genes from an African pygmy mouse, Mus minutoides. Sequence analysis indicates that exon 1 regions from these genes have undergone conversion events independent of those observed in other mouse species. Furthermore, the conversion events in all murine species are limited to exon 1 sequences. One such event involves the insertion and subsequent transfer of an entire codon between the two genes. Comparisons with other murine C beta sequences suggest that gene conversion has occurred on the order of every 0.3 Myr during the evolution of a family consisting of only two genes.

Animals

Gene trees and the origins of inbred strains of mice.

Extensive data on genetic divergence among 24 inbred strains of mice provide an opportunity to examine the concordance of gene trees and species trees, especially whether structured subsamples of loci give congruent estimates of phylogenetic relationships. Phylogenetic analyses of 144 separate loci reproduce almost exactly the known genealogical relationships among these 24 strains. Partitioning these loci into structured subsets representing loci coding for proteins, the immune system and endogenous viruses give incongruent phylogenetic results. The gene tree based on protein loci provides an accurate picture of the genealogical relationships among strains; however, gene trees based upon immune and viral data show significant deviations from known genealogical affinities.

Algorithms

Positive Darwinian evolution in human influenza A viruses.

We earlier suggested that type A human influenza virus genes undergo positive Darwinian selection through immune surveillance. This requires more favorable amino acid replacements fixed in antigenic sites among the surviving lineages than among the extinct lineages. We now show that viral hemagglutinins fix proportionately more amino acid replacements in antigenic sites in the trunk of the evolutionary tree (survivors) than in the branches (nonsurvivors), demonstrating that type A human influenza virus is undergoing positive Darwinian evolution. The hemagglutinin gene is evolving 3 times faster than the nonstructural gene and the average age of the sampled nonsurvivors is only 1.6 years, so that extinction is not only common but rapid.

Amino Acid Sequence

Evolution of pig influenza viruses.

There is evidence that the nucleoprotein (NP) gene of the classical swine virus (A/Swine/1976/31) clusters with the early human strains at the nucleotide sequence level, while at the level of the amino acid sequence, as defined by consensus amino acids and in functional tests, its NP is clearly "avian like." Therefore it was suggested that the Sw/31 NP had been recently under strong selection pressure, possibly caused by reassortment with other avian influenza genes, whose gene products have to cooperate intimately with NP (Gammelin et al., 1989. Virology 170, 71-80). This suggestion has been investigated by sequencing the genes of internal and nonstructural proteins of Sw/31. The data on these sequences and on the phylogenetic trees are not in accordance with that suggestion: all these genes cluster with the early human strains at the nucleotide level while, at the level of the amino acid sequence, most of them are more closely related to the avian strains, thus resembling NP in this respect. This indicates that these genes rather evolved concomitantly with the NP gene. Our data are in agreement with the suggestion that, at about the time of the Spanish Flu (1918/19), a human influenza A (H1N1) virus entered the pig population. Furthermore, it is known that the NP of the human influenza A viruses--in contrast to that of the avian and swine strains--has been under strong selection pressure to change (Gammelin et al., 1990. Mol. Biol. Evol. 7, 194-200. Gorman et al., 1990a. J. Virol. 64, 1487-1497). Thus, after transfer of a human strain into pigs, the selection pressure might be released, enabling the NP and the other genes of the swine virus to evolve back to the optimal avian sequences, especially at the functionally important consensus positions. The swine influenza viruses circulating since 1979 in Northern Europe--represented by A/Swine/Germany/2/81 (H1N1)--have all genes, so far examined, derived from an avian influenza virus pool and are different from the classical swine viruses.

Animals