Is there selection against wobble in codon-anticodon pairing?

Among amino acid codons that require a third-position pyrimidine, there is a significant bias favoring the use of cytidine over uracil in MS2 phage RNA. This could arise from selection against wobble pairing in the interaction of transfer RNA and messenger RNA. Among amino acid codons with fourfold degeneracy, there is a bias favoring pyrimidines over purines.

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.

Evolution in inbred strains of mice appears rapid.

Genetic variation at 97 loci in ten commonly used inbred strains of mice is greatly in excess of that expected under current assumptions. Evidence against all of the readily apparent explanations is presented and the possibility of early selection for heterozygosity or of conversion is suggested. The common ancestor of these strains is estimated to have occurred about 150 years ago.

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.

Predicting the evolution of human influenza A.

Eighteen codons in the HA1 domain of the hemagglutinin genes of human influenza A subtype H3 appear to be under positive selection to change the amino acid they encode. Retrospective tests show that viral lineages undergoing the greatest number of mutations in the positively selected codons were the progenitors of future H3 lineages in 9 of 11 recent influenza seasons. Codons under positive selection were associated with antibody combining site A or B or the sialic acid receptor binding site. However, not all codons in these sites had predictive value. Monitoring new H3 isolates for additional changes in positively selected codons might help identify the most fit extant viral strains that arise during antigenic drift.

Evolution of human influenza A viruses over 50 years: rapid, uniform rate of change in NS gene.

Variation in influenza A viruses was examined by comparison of nucleotide sequences of the NS gene (890 bases) of 15 human viruses isolated over 53 years (1933 to 1985). Changes in the genes accumulate with time, and an evolutionary tree based on the maximum parsimony method can be constructed. The evolutionary rate is approximately 2 X 10(-3) substitution per site per year in the NS genes, which is about 10(6) times the evolutionary rate of germline genes in mammals. This uniform and rapid rate of evolution in the NS gene is a good molecular clock and is compatible with the hypothesis that positive selection is operating on the hemagglutinin (or perhaps some other viral genes) to preserve random mutations in the NS gene.

Homology a personal view on some of the problems.

There are many problems relating to defining the terminology used to describe various biological relationships and getting agreement on which definitions are best. Here, I examine 15 terminological problems, all of which are current, and all of which relate to the usage of homology and its associated terms. I suggest a set of definitions that are intended to be totally consistent among themselves and also as consistent as possible with most current usage.

Random sequences.

The comparison of protein or nucleic acid sequences frequently leads to observations whose improbability can be tested only by Monte Carlo techniques that require randomizing the sequences being compared. Two decisions need to be made. One is whether one demands a resulting random sequence to have the properties of the original sequence (a shuffled sequence) or only expects it to have them (a representative sequence). The second decision concerns the properties of the sequence of which two are composition and nearest-neighbor frequencies. It is shown that biased nearest-neighbor frequencies can significantly affect the probability of observing a given result. Methods for producing random sequences according to these decisions are given.

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.

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.

Mapping the order of DNA restriction fragments.

A straightforward method was designed for mapping the order of DNA restriction fragments obtained by a double and two single digestions, without the necessity of using a computer or a radioactive label. All possible solutions compatible with a pre-set level of error in the determination of sequence lengths are obtained. The primary assumptions are given, and the appropriate modifications of the algorithm are presented as a function of any assumptions one is unable (or unwilling) to make. Use of the method in connection with end-labeled fragments is also described.

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.

Recent evolutionary divergence of plasma prekallikrein and factor XI.

The evolution in mammals of the zymogens of the contact activation system of coagulation (factor XII, prekallikrein and factor XI) has been investigated. The NH2-terminal sequences of human plasma prekallikrein and the heavy and light chains of kallikrein have been determined and compared with those of bovine prekallikrein and of human and bovine factors XII and XI. The human and bovine NH2-terminal sequences of the light chains (catalytic polypeptide) show striking similarities both among themselves and with those of the catalytic polypeptide chains of other coagulation and digestive proteases, indicating a common origin. Comparison of the NH2-terminal sequences of human prekallikrein with those of the bovine prekallikrein and human bovine factors XIa and XIIa indicates a common origin of the heavy chain of kallikrein and factor XIa, different from that of either factor XIIa or other known amino acid sequences. Ancestral sequences for human and bovine prekallikrein and factor XI, deduced by genetic analysis of the minimum number of base changes indicate that the NH2-terminus of prekallikrein and factor XI have evolved at about the same rate. The estimated time for the gene duplication was about 124 million years ago, a value consistent with the age of the mammals.