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Biomedical subjects

W M Fitch

Publications and source records attributed to W M Fitch.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Phylogenetic relationship of the nonstructural (NS) genes of influenza A viruses.

Phylogenetic trees were constructed using 38 sequences of the A group and 10 sequences of the B group of the NS gene of influenza A viruses. Within the A group we found avian as well as mammalian influenza a viruses, while within the B group exclusively avian strains were found. The avian and human NS genes of the A group were derived from a common ancestor existing at about 1912. At 13 positions of the amino acid sequences of the NS1 protein two subtypes of the A group can be differentiated, a human and a non-human subtype. Starting at the time of the introduction of an avian PB1 gene into human strains during the antigenic shift at 1957 the NS1 protein of the human strains came under an enhanced selection pressure which might indicate a cooperation of the NS1 protein with and adaptation of the NS1 protein on the newly introduced PB1 gene. Such a selection pressure on the NS2 protein is completely missing. Comparison of all sequences of the NS1 protein revealed four highly conserved regions within the amino-terminal half of the molecule. One of this regions seems to contain the nuclear migration signal. The carboxy-terminal half is completely variable and seems to be dispensable.

Amino Acid Sequence↗
PubMed1990

Derivation of the nucleoproteins (NP) of influenza A viruses isolated from marine mammals.

The nucleoprotein (NP) genes of influenza viruses were sequenced from a variety of virus isolates derived from marine mammals: whales from the Pacific and Atlantic oceans, seal and gull from the Western Atlantic, and a tern from the Caspian Sea. In comparison to published NP sequences, we found pairs of NPs derived from avian and marine mammal isolates to be closely related, e.g., the gull-whale and mallard-seal pairs from the Atlantic Coast of the USA and the tern-Pacific Ocean whale pair of the Eastern Hemisphere. Our analysis suggests that influenza viruses have been independently introduced into marine mammals from avian sources for each of our three examples. Furthermore, the closeness of the relationship in these avian-mammalian NP pairs indicates that the introductions are relatively recent. The sequences of these marine mammal NPs are avian-like and can be clearly distinguished from human NPs. Our results provide further support of interspecies transmission of influenza A viruses from the avian host reservoir directly to mammalian hosts.

Amino Acid Sequence↗
PubMed1990

Correcting parsimonious trees for unseen nucleotide substitutions: the effect of dense branching as exemplified by ribonuclease.

In a study of mammalian ribonuclease evolutionary rates, we applied the Fitch-Bruschi correction to reduce the bias caused by an unequal sampling of taxa in different lineages. The correction was clearly appropriate but only up to a point. The analysis showed that the sampling of taxa within the pecora was sufficiently intense that no correction for unseen, amino acid-changing, nucleotide substitutions was required. It was also found that the ribonuclease gene was duplicated at least twice at the origin of the pecoran branch of the artiodactyls.

Animals↗
PubMed1990

Phosphoprotein and nucleocapsid protein evolution of vesicular stomatitis virus New Jersey.

The entire phosphoprotein (P) and nucleocapsid (N) protein gene sequences and deduced amino acid sequences for 18 selected vesicular stomatitis virus isolates representative of the natural genetic diversity within the New Jersey serotype are reported. Phylogenetic analysis of the data using maximum parsimony allowed construction of evolutionary trees for the individual genes and the combined N, P, and glycoprotein (G) genes of these viruses. Virtually identical rates of nucleotide substitutions were found for each gene, indicating that evolution of these genes occurs at essentially the same rate. Although up to 19 and 17% sequence differences were evident in the P and N genes, respectively, no variation in gene length or evidence of recombinational rearrangements was found. However, striking evolutionary differences were observed among the amino acid sequences of vesicular stomatitis virus New Jersey N, P, and G proteins. The N protein amino acid sequence was the most highly conserved among the different isolates, indicating strong functional and structural constraints. Conversely, the P protein amino acid sequences were highly variable, indicating considerably fewer constraints or greater evolutionary pressure on the P protein. Much of the remarkable amino acid variability of the P protein resided in a hypervariable domain located between amino acids 153 and 205. The variability within this region would be consistent with it playing a structural role as a spacer to maintain correct conformational presentation of the separate active domains of this multifunctional protein. In marked contrast, the adjacent domain I of the P protein (previously thought to be under little evolutionary constraint) contained a highly conserved region. The colocalization of a short, potentially functional overlapping open reading frame to this region may explain this apparent anomaly.

Amino Acid Sequence↗
PubMed1989

Glycoprotein evolution of vesicular stomatitis virus New Jersey.

A T1 ribonuclease fingerprinting study of a large number of virus isolates had previously demonstrated that considerable genetic variability existed among natural isolates of the vesicular stomatitis virus (VSV) New Jersey (NJ) serotype [S.T. Nichol (1988) J. Virol. 62, 572-579]. Based on these results, 34 virus isolates were chosen as representing the extent of genetic diversity within the VSV NJ serotype. We report the entire glycoprotein (G) gene nucleotide sequence and the deduced amino acid sequence for each of these viruses. Up to 19.8% G gene sequence differences could be seen among NJ serotype isolates. Analysis of the distribution of nucleotide substitutions relative to nucleotide codon position revealed that third position changes were distributed randomly throughout the gene. Third base changes constituted 84% of the observed nucleotide substitutions and affected 89% of the third base positions located in the G gene. Only three short oligonucleotide stretches of complete sequence conservation were observed. The remaining nucleotide changes located in the first and second positions were not distributed randomly, indicating that most of the amino acids coded by the G gene cannot be altered without reducing the fitness of the VSV NJ serotype viruses. Despite these constraints, up to 8.5% amino acid differences were observed between virus isolates. These differences were located throughout the G protein including regions adjacent to defined major antibody neutralization epitopes. Apparent clusters of amino acid substitutions were present in the hydrophobic signal sequence, transmembrane domain, and within the cytoplasmic domain of the G protein. A maximum parsimony analysis of the G gene nucleotide sequences allowed construction of a phylogram indicating the evolutionary relationship of these viruses. The VSV NJ serotype appears to contain at least three distinct lineages or subtypes. All recent virus isolates from the United States and Mexico are within subtype I and appear to have evolved from an ancestor more closely related to the Hazelhurst historic strain than other older strains. The implications of these findings for the evolution, epizootiology, and classification of these viruses are discussed.

Amino Acid Sequence↗
PubMed1977

The restriction of codon ambiguity on the basis of known variants.

The genetic code may be used to formulate the nucleotide sequence of a messenger RNA from the known amino acid sequence of a protein. Unfortunately, the degeneracy of the code means that there will be ambiguity in the nucleotide assignments in a third or more of the positions. A simple procedure is given that utilizes the information of known genetic variants to reduce that ambiguity. Problems associated with silent polymorphism are treated. The human alpha and beta hemoglobins are used to exemplify the technique. A total of 68 nucleotides in the two sequences are thereby made less ambiguous. One reduction leads to a nucleotide inconsistent with the result of the recently published beta hemoglobin sequence.

Base Sequence↗
PubMed1977

Primary structure of cholera toxin beta-chain: a glycoprotein hormone analog?

The completed sequence of the beta-chain of cholera toxin (103 amino acid residues) was compared to the beta-chains of chorionic gonadotropin, thyrotropin, luteinizing, and follicle stimulating hormones. The overall chemical similarity of the toxin beta-chain to the hormones was not statistically different from random; however, a comparison of the first 40 residues of the toxin beta-chain to the glycoprotein hormones revealed a segment of the hormones which was significantly chemically similar. The probability was less than .003 that the similarity was due to chance.

Adenylyl Cyclases↗
PubMed1977

Phylogenies constrained by the crossover process as illustrated by human hemoglobins and a thirteen-cycle, eleven-amino-acid repeat in human apolipoprotein A-I.

Examination of human apolipoprotein A-I revealed a segment of eleven amino acids that repeated itself 13 times in succession without any additional intervening amino acids between the beginning of the repeats (amino acid 93) and their end at the carboxyl terminus of the sequence. The segments are not identical, but the pattern of their physical and chemical properties is highly conserved. The pattern is shown to be suitable to the formation of alpha helices with an amphipathic character consistent with the formation of a micellar structure, a process entirely appropriate to the protein's known function in the blood stream as a lipid carrier. The simplest hypothesis to account for repeated segments is a series of unequal crossovers. But such a series implies that some segments are more closely related to each other than they are to others, that is, they have a "phylogenetic" relationship. It is shown that only a small fraction of all possible phylogenies are consistent with a set of segments arising by simple unequal crossing over. Nevertheless, it is shown that the apolipoprotein A-I segments are readily interpretable as the result of simple unequal crossing over. Moreover, the crossover constraint applies with as much force to segments larger than a gene as to segments within a gene, and this is shown to require that the human gamma (Gly) hemoglobin gene lie to the left, rather than to the right, of the other non-alpha human hemoglobin genes, a conclusion for which there is no direct genetic evidence currently available.

Amino Acid Sequence↗