Christopher Wills

• University of California, San Diego

When Darwin visited the Galapagos archipelago, he observed that, in spite of the islands’ physical similarity, members of species that had dispersed to them recently were beginning to diverge from each other. He postulated that these divergences must have resulted primarily from interactions with sets of other species that had also diverged across...

[This corrects the article DOI: 10.1371/journal.pone.0156913.].

Studies of forest dynamics plots (FDPs) have revealed a variety of negative density-dependent (NDD) demographic interactions, especially among conspecific trees. These interactions can affect growth rate, recruitment and mortality, and they play a central role in the maintenance of species diversity in these complex ecosystems. Here we use an equal...

Text A, Text B, Figs A-F. (DOCX)

Strong evidence for introgression of Neanderthal genes into parts of the modern human gene pool has recently emerged. The evidence indicates that some populations of modern humans have received infusions of genes from two different groups of Neanderthals. One of these Neanderthal groups lived in the Middle East and Central Europe and the other grou...

All evolutionary change can be traced to alterations in allele frequencies in populations over time. DNA sequencing on a massive scale now permits us to follow the genetic consequences as our species has diverged from our close relatives and as we have colonized different parts of the world and adapted to them. But it has been difficult to disentan...

The spliceosome, a sophisticated molecular machine involved in the removal of intervening sequences from the coding sections of eukaryotic genes, appeared and subsequently evolved rapidly during the early stages of eukaryotic evolution. The last eukaryotic common ancestor (LECA) had both complex spliceosomal machinery and some spliceosomal introns,...

Pseudo-symmetry of the Sm beta-barrel. (A) Pseudo-symmetry within the molecule: the N-terminal half is colored orange; C-terminal half is green. (B) Superimposition between two halves of the beta-barrel. (2.17 MB TIF)

Alignment of 355 Sm/lsm genes from bacteria, archaea and eukaryotes. Shading of the alignment is by the level of conservation. The six most conserved residues are labeled with red dots. Secondary structure assignments are displayed above the alignment. (7.03 MB JPG)

The variable loop region in Sm/lsm beta-barrel. (A) Structure of the bacterial Sm-line protein Hfq. (B) Structure of archaeal and eukaryotic Sm/lsm proteins. (C) Differences in length of the variable loop in the bacterial, archaeal and eukaryotic (SmB) small beta-barrel. (3.38 MB TIF)

Relationship between SH3 and OB folds. (3.32 MB TIF)

RNA binding in the Sm/Lsm ring. (A) Structure of the archaeal heptameric ring (PDB code 1M8V) and its interaction with RNA. (B) Structure of the bacterial hexameric ring (PDB code 1KQ2) and its interaction with RNA. (C) Superimposition between bacterial and archaeal beta-barrels; residues colored in green are involved in interaction with RNA. (D) S...

Phylogenetic tree of eukaryotic Sm and Lsm sequences reconstructed using Bayesian approach (Mr. Bayes). Tree built from eukaryotic Lsm sequences using Bayesian inference (2,000,000 iterations). (0.60 MB TIF)

Phylogenetic tree of eukaryotic Sm and Lsm sequences reconstructed using Bayesian approach (Mr. Bayes). Tree built from eukaryotic Sm sequences using Bayesian inference B (2,000,000 iterations). (0.56 MB TIF)

Supplementary Materials (0.04 MB DOC)

Phylogenetic tree of eukaryotic Sm and Lsm sequences reconstructed using Bayesian approach (Mr. Bayes). Tree built from eukaryotic Sm/Lsm sequences using Bayesian inference (3,000,000 iterations). (0.78 MB TIF)

Level of sequence conservation as calculated for inter-family alignment (divergence before LECA) and intra-family alignment (divergence since LECA). (0.04 MB DOC)

Tropical forests vary substantially in the densities of trees of different sizes and thus in above-ground biomass and carbon stores. However, these tree size distributions show fundamental similarities suggestive of underlying general principles. The theory of metabolic ecology predicts that tree abundances will scale as the -2 power of diameter. D...

The theory of metabolic ecology predicts specific relationships among tree stem diameter, biomass, height, growth and mortality. As demographic rates are important to estimates of carbon fluxes in forests, this theory might offer important insights into the global carbon budget, and deserves careful assessment. We assembled data from 10 old-growth...

An ecological community's species diversity tends to erode through time as a result of stochastic extinction, competitive exclusion, and unstable host-enemy dynamics. This erosion of diversity can be prevented over the short term if recruits are highly diverse as a result of preferential recruitment of rare species or, alternatively, if rare specie...

Infections of adenovirus type 4 (Ad4) and Ad7 were discovered among previously vaccinated individuals through febrile respiratory illness surveillance at military recruit camps. Genetic analysis was performed on these isolates and a sample of adenovirus isolates from unvaccinated patients. Antigenic regions of the adenovirus hexon gene from 21 vacc...

Background Adenoviral respiratory infections cause great morbidity in military basic training. Vaccines preventing illness from adenovirus serotypes 4 and 7 (AV4 and AV7) were successfully used from 1971-1999 and may be available again in coming years. Cases of adenovirus AV4 and AV7-associated febrile respiratory illness found in previously vaccin...

This review is intended to be a global examination of the various hypotheses for the origin and maintenance of genetic recombination and out-crossing, with a look at the surprisingly limited amounts of experimental evidence that has been obtained in order to distinguish among them. It is designed for the reader who wishes an overview of the current...

Saccharomyces cerevisiae is a yeast commonly used in baking and a frequent colonizer of human mucosal surfaces. It is considered relatively nonpathogenic in immunocompetent adults (J. N. Aucott, J. Fayan, H. Grossnicklas, A. Morrissey, M. M. Lederman, and R. A. Salata, Rev. Infect. Dis. 12:406-411, 1990). We present a case of S. cerevisiae fungemia...

Microsatellites (short tandem polynucleotide repeats) are found throughout eukaryotic genomes at frequencies many orders of magnitude higher than the frequencies predicted to occur by chance. Most of these microsatellites appear to have evolved in a generally neutral manner. In contrast, microsatellites are generally absent from bacterial genomes e...

We have demonstrated hypervariability of native short-motif repeats (microsatellites) in Escherichia coli. Twenty-five of the longest microsatellites in the E. coli genome were identified. These were analysed for length variability among 22 wild-type (non-mutator) isolates from the E. coli collection of reference (ECOR). Non-coding mononucleotide r...

The evolutionary tuning of mutational processes may play a key role in prokaryotic evolution, particularly among pathogens. In this paper we review the evidence that genetic systems controlling the rate and spectrum of heritable mutations have evolved to optimize levels of adaptive variation and rates of genetic change.

Microsatellite enrichment is an excess of repetitive sequences characteristic to all studied eukaryotes. It is thought to result from the accumulated effects of replication slippage mutations. Enrichment is commonly measured as the ratio of the observed frequency of microsatellites to the frequency expected to result from random association of nucl...

We show the presence of numerous short tandem repeats in the human cytomegalovirus (HCMV) genome and assess their usefulness as molecular markers. The genome is shown to contain at least 24 microsatellite regions that exhibit length polymorphisms. Insertion-deletion polymorphisms at these short tandem repeats are common (80% of repeats examined are...

Phylogenetic trees for the four extant species of African hominoids are presented, based on mtDNA control region-1 sequences from 1,158 unique haplotypes. We include 83 new haplotypes of western chimpanzees and bonobos. Phylogenetic analysis of this enlarged database, which takes intraspecific geographic variability into account, reveals different...

We applaud the notion recently highlighted by Ann Gibbons (News Focus, 4 Sept., p. [1433][1]) about “Pushing a primate genome project.” There is much to be learned by comparing human genomic sequences with those of other primates, particularly those of our closest evolutionary cousins, the great

Twelve patients infected with the human immunodeficiency virus (HIV) and with CD4 cell counts below 100 cells/microliter received fluconazole daily (200 mg; five patients) or weekly (400 mg; seven patients) for fungal prophylaxis during a 6-month period. Oropharyngeal swabs were taken at regular intervals in order to detect colonization with Candid...

Competitions between matched pairs of diploid strains of Saccharomyces cerevisiae, one capable of undergoing sexual recombination (MAT-heterozygous) and the other not (MAT-homozygous), have proved useful for measuring the effects of mitotic and meiotic recombination and DNA repair on competitive ability in this organism. Overall competitive differe...

We examined the distributions of short tandemly repeated DNAs (microsatellites) in nine complete microbial genomes (Saccharomyces cerevisiae, Archaeoglobus fulgidus, Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Methanococcus jannaschii, Mycoplasma pneumoniae, M. genitalium, and Synechocystis PCC6803.) These repeats contribute diff...

Sequence diversity at a coding-region microsatellite locus of two diploid Candida species was surveyed. Twenty-one alleles from fourteen strains of Candida albicans and three alleles from two strains of the closely related Candida dubliniensis were sequenced. Results show independent length variation in two contiguous hexanucleotide repeats, one no...

While mitochondrial sequences can be used to probe the time and place of the mitochondrial 'Eve,' nuclear genes can be used to ask a slightly different question: when did humans (members of the genus Homo) or their hominid precursors (the hominids) first leave Africa and fan out over Asia and Europe? If they did so recently, it seems likely that th...

Abstract We describe the identification of polymorphic microsatellite loci in the pathogenic yeast, Candida albicans. A search for all coding-region microsatellites with more than four repeats that can be found in Candida sequences in GenBank was conducted. Nine such microsatellite sequences consisting of trinucleotide motifs were found. Three of t...

A method is presented for removing recent homoplastic events from a phylogenetic tree. This ''topiary pruning'' method produces a series of progressively modified duplicates of the original set of data, from which more and more of the most recent substitutions have been removed. The edited sets of data have increased amounts of information per rema...

A method is presented for removing recent homoplastic events from a phylogenetic tree. This "topiary pruning" method produces a series of progressively modified duplicates of the original set of data, from which more and more of the most recent substitutions have been removed. The edited sets of data have increased amounts of information per remain...

Methods of phylogenetic analysis are presented that result in corrections of highly biased data sets, particularly those in which there are great differences between mutation and/or substitution rates from one nucleotide site to another along a DNA sequence. Two approaches are discussed. In the first, pairwise comparisons of a set of sequences are...

Various estimates of the time at which the human mitochondrial Eve lived have ranged from as little as 60,000 yr to more than 500,000 yr ago. Because of this immense range, it is impossible to distinguish between single-origin and multiple-origins hypotheses for the evolution of our species. In an attempt to reduce the uncertainty, I have examined...

Various estimates of the time at which the human mitochondrial Eve lived have ranged from as little as 60,000 yr to more than 500,000 yr ago. Because of this immense range, it is impossible to distinguish between single-origin and multiple-origins hypotheses for the evolution of our species. In an attempt to reduce the uncertainty, I have examined...

We show here that the method of genomic denaturing gradient electrophoresis (gDGGE) can be used to examine any gene that has been previously cloned and sequenced, and to detect and approximately localize within the gene the majority of its polymorphisms. By using pooled-DNA gDGGE, many different samples can be scanned on a single gel. Further, the...

Models of group selection are complex, awkward, and tend to be balanced on a knife edge of perilous assumptions. Sociologists and geneticists apply them to something as complex as human society at their peril. I suggest an alternative model based on the maintenance of genetic heterogeneity for behavior within groups. This can occur by means of slig...

When investigators undertake searches of DNA databases, they normally discard large numbers of alignments that demonstrate very weak resemblances to each other, retaining only those that show statistically significant levels of resemblance. We show here that a great deal of information can be extracted from these weak alignments by examining them e...

Sexual (MATa/α) and sexual (MATa/a) strains of the yeast Saccharomyces cerevisiae, which are completely isogenic except at the MAT locus, were compared in their response to ultraviolet radiation. The effects of UV on survival, mitotic intragenic recombination, photoreactivation, and transformation efficiency with UV-irradiated plasmid DNA were exam...

Models that purport to explain the maintenance of MHC polymorphism must be able to explain a variety of phenomena. (1) The range of MHC allele frequencies at some of the loci is very large, with some alleles quite common and many others rare, while at others the range of allele frequencies is far narrower. (2) MHC alleles and their frequencies ofte...

This review briefly surveys the literature on the nature, regulation, genetics, and molecular biology of the major energy-yielding pathways in yeasts, with emphasis on Saccharomyces cerevisiae. While sugar metabolism has received the lion's share of attention from workers in this field because of its bearing on the production of ethanol and other m...

Relation entre la distance geographique et la phylogenese etudie chez des populations de la souris Peromyscus maniculatus des iles du detroit de Californie a l'aide de donnees morphologiques, biologiques et du RFLP de l'ADN mitochondrial

Growth and development from infancy to age 18 years in tasters and non-tasters of phenylthiocarbamide (P.T.C.) were studied in 50 female and 44 male subjects. Taster girls reached all indices of maturation an average of 3.8 months earlier than non-taster girls. The reverse was true for boys, non-tasters maturing on average 6.2 months earlier than t...

Selection for resistance to allyl alcohol in respiration-incompetent Saccharomyces cerevisiae produces a high proportion of mutants that can be localized within the ADH2 structural gene and that still, because of the type of selection employed, retain enzyme activity. We show here that a similar type of selection produces a similarly high proportio...

Documented examples of heterosis attributable to overdominance at specific protein-encoding gene loci have rarely been reported, the association of sickle cell hemoglobin with malarial resistance being the best documented example of this phenomenon. Here we report an example of overdominance that is temperature- and allyl alcohol-dependent and due...

Mitochondrial DNA (mtDNA) from 131 deer mice, Peromyscus maniculatus, collected on the eight California Channel Islands and from seven southern California mainland locations, was isolated and analyzed for restriction endonuclease fragment polymorphisms. A total of 26 mtDNA genotypes were distinguishable among the deer mice sampled. All of the islan...

Mitochondrial DNA (mtDNA) from 131 deer mice, Peromyscus maniculatus, collected on the eight California Channel Islands and from seven southern California mainland locations, was isolated and analyzed for restriction endonuclease fragment polymorphisms. A total of 26 mtDNA genotypes were distinguishable among the deer mice sampled. All of the islan...

Selection for allyl alcohol resistance in respiratory incompetent yeast is a highly specific method for isolating functional mutations at ADH1, the gene coding for the cytoplasmic alcohol dehydrogenase, ADHI. Because of the nature of this selection scheme, the ADHI activity of such mutants is retained, but the kinetic characteristics of the enzymes...

Two mutants of Saccharomyces cerevisiae, ccr1 and tpy1, have been found to interfere with the transport of small molecules across the inner mitochondrial membrane. Both also have the effect of interfering with the synthesis of a number of cytoplasmically located enzymes involved in gluconeogenesis, even when the cells are released from glucose repr...

A mutant lacking L-lactate dehydrogenase (EC 1.1.2.3) of Saccharomyces cerevisiae was isolated by its inability to grow on minimal medium with L-lactate as a carbon source. A simple activity gel assay for visualization of this enzyme and the two D-lactate dehydrogenases in this organism (EC 1.1.2.4 and 1.1.1.28) was developed. This enabled us to sc...

An activity gel assay for fructose-1,6-bisphosphatase (FBP), the enzyme catalyzing the final step in gluconeogenesis in yeast, has been developed which can be used in conjunction with spectrophotometric assays to show that it is tightly co-regulated with the inducible alcohol dehydrogenase, ADHII. Both enzymes are repressed coordinately in aerobica...

A single-gene nuclear mutant has been isolated in Saccharomyces cerevisiae which cannot grow on minimal medium supplemented with ethanol, acetate, pyruvate, aspartate, or oxaloacetate as sole carbon sources. It will grow on complete medium with these carbon sources, and on minimal medium with dextrose as carbon source. The only supplement which wil...

We have reported elsewhere (Wills, C. and Martin, T. (1984) Biochim. Biophys. Acta 782, 274-284) that one or more mitochondrial transport systems may be involved in the regulation of the inducible alcohol dehydrogenase of yeast, ADH-II. In order to investigate this phenomenon further, it was necessary to determine which of these systems operate in...

The alcohol dehydrogenases in yeast form one of the best-understood eukaryotic regulatory systems at the genetic level, but very little is known about their regulation at the biochemical level. We report on a simple whole-cell assay system for the induction of the inducible isozyme, alcohol dehydrogenase II, which has been used to show that no sing...

Because our approach to the problems of molecular evolution in the laboratory is rather different from that of most of the other workers contributing to this volume, I would like to begin this review of our recent work on yeast alcohol dehydrogenase with a historical note.

Selection of petite strains of yeast (that is, strains unable to respire aerobically) on media containing allyl alcohol will result in enrichment for mutants at the ADC1 locus. This locus codes for the constitutive alcohol dehydrogenase, ADH-I, which is primarily responsible for the production of ethanol in yeast. The mutant enzymes are functional,...

The two alcohol dehydrogenases of Zymomonas mobilis, a fermentative bacterium, have been characterized kinetically and physiologically, and a preliminary biochemical characterization has been made. The two isozymes are separable electrophoretically and have been purified separately by affinity chromatography. One, a tetramer, has a subunit molecula...

The two major alcohol dehydrogenases of yeast are coded by separate nuclear genes, and show 95% amino acid homology. Nonetheless, the “constitutive” ADH, ADH-I, preferentially catalyzes the reaction acetaldehyde → ethanol, and the inducible ADH, ADH-II, preferentially catalyzes the reverse reaction. Linked and non-linked mutants rendering ADH-II co...

The structures of the two cytoplasmic isozymes of alcohol dehydrogenase in a haploid strain of the yeast Saccharomyces cerevisiae have been compared and related to a commercial preparation of the protein that was previously analyzed. The constitutive isozyme I (purified from a petite cell incapable of mitochondrial respiration) is found to correspo...

A METHOD has been developed1-3 for selecting mutants of the structural gene for the constitutive alcohol dehydrogenase of the yeast Saccharomyces cerevisiae. These mutations alter but do not destroy the function of the enzyme. We report here the amino acid substitutions in two of these mutants, and examine the probable effects of these substitution...

Repeated selection of petite (respiratorily incompetent) Saccharomyces cerevisiae on medium containing allyl alcohol, both on plates and in the turbidostat, results in mutants with a remarkably similar response. Most of the mutations affect the constitutive alcohol dehydrogenase, resulting in enzymes with a cathodal shift in electrophoretic mobilit...

Mutants of yeast alcohol dehydrogenase have been produced that protect the cell against the poisonous aldehyde acrolein by increasing the NADH-NAD ratio. The altered properties include changes both in binding constants and in cooperativity. Such mutants may be useful in exploring the nature of adaptation at the molecular level.

It is shown, through theory and computer simulations of outbreeding Mendelian populations, that there may be conditions under which a balance is struck between two facotrs. The first is the advantage of random assortment, which will, when multilocus selection is for intermediate equilibrium values, lead to higher average heterozygosity than when li...

Electrophoretically distinguishable mutants of yeast alcohol dehydrogenase with specifically altered kinetics have been obtained using a modification of the allyl alcohol selection technique of Megnet. The modification depends on the fact that mutant cells producing no detectable ADH or only the ADH sequestered inside the mitochondria cannot become...

A number of separate strains of Drosophila pseudoobscura were inbred for 38 generations of brother-sister mating with forced heterozygosity for two alleles of either the octanol dehydrogenase or esterase-5 locus. Crosses were set up within each of these inbred lines such that simple mendelian ratios were expected, and eggs from these crosses were p...

A scheme is proposed for dividing up genetic variability in natural populations. Some of the variability initially produced by mutation is unconditionally deleterious and is removed more or less rapidly. Some is adaptively useful in the short run but subject to a high segregational load and therefore also eliminated or modified, but more slowly. So...

Conditional heterosis associated with two isoallelic forms of octanol dehydrogenase in Drosophila pseudoobscura has been detected in flies that have been (a) inbred for several generations to make the background genotype as homozygous as practicable, and (b) grown on a medium containing a small amount of octanol. The heterosis was first found in in...

KIMURA and others1-4 have suggested that most observed isoallelic variation in natural populations is maintained by mutation pressure and drift alone, and that selection is not involved. This viewpoint has been criticized5,6, and several models7-11 have been proposed which permit large amounts of selectively maintained polymorphism without impossib...