Stanley Sawyer

The cost of inbreeding in Arabidopsis

Population geneticists have long sought to estimate the distribution of selection intensities among genes of diverse function across the genome. Only recently have DNA sequencing and analytical techniques converged to make this possible. Important advances have come from comparing genetic variation within species (polymorphism) with fixed differences between species (divergence). These approaches have been used to examine individual genes for evidence of selection. Here we use the fact that the time since species divergence allows combination of data across genes. In a comparison of amino-acid replacements among species of the mustard weed Arabidopsis with those among species of the fruitfly Drosophila, we find evidence for predominantly beneficial gene substitutions in Drosophila but predominantly detrimental substitutions in Arabidopsis. We attribute this difference to the Arabidopsis mating system of partial self-fertilization, which corroborates a prediction of population genetics theory that species with a high frequency of inbreeding are less efficient in eliminating deleterious mutations owing to their reduced effective population size.

Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila.

We have estimated the selective effects of amino acid replacements in natural populations by comparing levels of polymorphism in 91 genes in African populations of Drosophila melanogaster with their divergence from Drosophila simulans. The genes include about equal numbers whose level of expression in adults is greater in males, greater in females, or approximately equal in the sexes. Markov chain Monte Carlo methods were used to sample key parameters in the stationary distribution of polymorphism and divergence in a model in which the selective effect of each nonsynonymous mutation is regarded as a random sample from some underlying normal distribution whose mean may differ from one gene to the next. Our analysis suggests that ≈95% of all nonsynonymous mutations that could contribute to polymorphism or divergence are deleterious, and that the average proportion of deleterious amino acid polymorphisms in samples is ≈70%. On the other hand, ≈95% of fixed differences between species are positively selected, although the scaled selection coefficient (Nes) is very small. We estimate that ≈46% of amino acid replacements have Nes < 2, ≈84% have Nes < 4, and ≈99% have Nes < 7. Although positive selection among amino acid differences between species seems pervasive, most of the selective effects could be regarded as nearly neutral. There are significant differences in selection between sex-biased and unbiased genes, which relate primarily to the mean of the distributions of mutational effects and the fraction of slightly deleterious and weakly beneficial mutations that are fixed.

Sexual dimorphism and adaptive radiation in Anolis lizards.

Sexual dimorphism is widespread and substantial throughout the animal world. It is surprising, then, that such a pervasive source of biological diversity has not been integrated into studies of adaptive radiation, despite extensive and growing attention to both phenomena. Rather, most studies of adaptive radiation either group individuals without regard to sex or focus solely on one sex. Here we show that sexual differences contribute substantially to the ecomorphological diversity produced by the adaptive radiations of West Indian Anolis lizards: within anole species, males and females occupy mostly non-overlapping parts of morphological space; the overall extent of sexual variation is large relative to interspecific variation; and the degree of variation depends on ecological type. Thus, when sexual dimorphism in ecologically relevant traits is substantial, ignoring its contribution may significantly underestimate the adaptive component of evolutionary radiation. Conversely, if sexual dimorphism and interspecific divergence are alternative means of ecological diversification, then the degree of sexual dimorphism may be negatively related to the extent of adaptive radiation.

Bayesian Analysis Suggests that Most Amino Acid Replacements in Drosophila Are Driven by Positive Selection

One of the principal goals of population genetics is to understand the processes by which genetic variation within species (polymorphism) becomes converted into genetic differences between species (divergence). In this transformation, selective neutrality, near neutrality, and positive selection may each play a role, differing from one gene to the next. Synonymous nucleotide sites are often used as a uniform standard of comparison across genes on the grounds that synonymous sites are subject to relatively weak selective constraints and so may, to a first approximation, be regarded as neutral. Synonymous sites are also interdigitated with nonsynonymous sites and so are affected equally by genomic context and demographic factors. Hence a comparison of levels of polymorphism and divergence between synonymous sites and amino acid replacement sites in a gene is potentially informative about the magnitude of selective forces associated with amino acid replacements. We have analyzed 56 genes in which polymorphism data from D. simulans are compared with divergence from a reference strain of D. melanogaster. The framework of the analysis is Bayesian and assumes that the distribution of selective effects (Malthusian fitnesses) is Gaussian with a mean that differs for each gene. In such a model, the average scaled selection intensity (γ =Nes) of amino acid replacements eligible to become polymorphic or fixed is −7.31, and the standard deviation of selective effects within each locus is 6.79 (assuming homoscedasticity across loci). For newly arising mutations of this type that occur in autosomal or X-linked genes, the average proportion of beneficial mutations is 19.7%. Among the amino acid polymorphisms in the sample, the expected average proportion of beneficial mutations is 47.7%, and among amino acid replacements that become fixed the average proportion of beneficial mutations is 94.3%. The average scaled selection intensity of fixed mutations is +5.1. The presence of positive selection is pervasive with the single exception of kl-5, a Y-linked fertility gene. We find no evidence that a significant fraction of fixed amino acid replacements is neutral or nearly neutral or that positive selection drives amino acid replacements at only a subset of the loci. These results are model dependent and we discuss possible modifications of the model that might allow more neutral and nearly neutral amino acid replacements to be fixed.

A precise reconstruction of the emergence and constrained radiations of Escherichia coli O157 portrayed by backbone concatenomic analysis

Single nucleotide polymorphisms (SNPs) in stable genome regions provide durable measurements of species evolution. We systematically identified each SNP in concatenations of all backbone ORFs in 7 newly or previously sequenced evolutionarily instructive pathogenic Escherichia coli O157:H7, O157:H−, and O55:H7. The 1,113 synonymous SNPs demonstrate emergence of the largest cluster of this pathogen only in the last millennium. Unexpectedly, shared SNPs within circumscribed clusters of organisms suggest severely restricted survival and limited effective population sizes of pathogenic O157:H7, tenuous survival of these organisms in nature, source-sink evolutionary dynamics, or, possibly, a limited number of mutations that confer selective advantage. A single large segment spanning the rfb-gnd gene cluster is the only backbone region convincingly acquired by recombination as O157 emerged from O55. This concatenomic analysis also supports using SNPs to differentiate closely related pathogens for infection control and forensic purposes. However, constrained radiations raise the possibility of making false associations between isolates.

Isotropic random walks in a tree

SummaryLet T be an infinite homogeneous tree of order a+1. We study Markov chains {Xn} in T whose transition functions p(x, y)=A[d(x,y)] depend only on the shortest distance between x and y in the graph. The graph T can be represented as a symmetric space of a p-adic matrix group; we prove a series of results using essentially the spherical functions of this symmetric space. Theorem 1.d(Xn,x)∼β n a.s., where β>0 if A(0) ≠ 1, X0=x. Assuming {Xn} is strongly aperiodic, Theorem 2. p2(x, y)∼CRn/n3/2 for fixed x, y where R=∑φ(d) A(d)<1, and if E[d(X1, X0)2]<∞, Theorem 3. R(1−u, x, y) = ∑(1−u)npn(x, y)=Ca−d[exp(−du/β)+od(1)] as d=d(x,y)→∞ uniformly for 0≦u≦2. Using Theorem 3, we calculate the Martin boundary Dirichlet kernel of p(x, y) on T, which turns out to be independent of {itA(d)}. We also consider a “stepping-stone” model of a randomly-mating-and-migrating population on the nodes of T. If initially all individuals are distinct, then in generation n approximately half of the individuals of a given type are within βn of a typical one and essentially all are within 2βn.

Maximal Inequalities of Weak Type

for f(x) e LV(X). Applications are given, and a generalization to where the domain of {T.} is an F-space. Inequality (1) occurs in many different areas in analysis. Indeed, the proof of (1) is often a key step in a convergence proof; the two conditions on {TJ} are in many cases equivalent (see Corollary 1.2). In particular, one can often prove the almost everywhere divergence of some limit (2) by calculating (1) to be false. By a recent theorem of E. M. Stein [19], (1) follows from the almost everywhere convergence of (2) in many situations from Fourier analysis. For example, let {TJ} be a sequence of translation-invariant linear operators on LP(G), where G is a compact group or its homogeneous space and 1 ? p 0 and f(x) e LD(G). Another example of a theorem of this type is contained in [4]. As an example, let

Sequence analysis and classification of apparent recombinant begomoviruses infecting tomato in the Nile and Mediterranean basins

ABSTRACT Numerous whitefly-transmitted viral diseases of tomato have emerged in countries around the Nile and Mediterranean Basins the last 20 years. These diseases are caused by monopartite geminiviruses (family Gemini viridae) belonging to the genus Begomovirus that probably resulted from numerous recombination events. The molecular biodiversity of these viruses was investigated to better appreciate the role and importance of recombination and to better clarify the phylogenetic relationships and classification of these viruses. The analysis partitioned the tomato-infecting begomoviruses from this region into two major clades, Tomato yellow leaf curl virus and Tomato yellow leaf curl Sardinia virus. Phylogenetic and pairwise analyses together with an evaluation for gene conversion were performed from which taxonomic classification and virus biodiversity conclusions were drawn. Six recombination hotspots and three homogeneous zones within the genome were identified among the tomatoinfecting isolates and species examined here, suggesting that the recombination events identified were not random occurrences.

Molecular population genetic analysis of the streptokinase gene of Streptococcus pyogenes: mosaic alleles generated by recombination

To understand the mechanisms governing molecular evolution of the streptokinase gene (skn), a 384 bp DNA fragment encoding two variable regions of the molecule was characterized in 47 isolates of Streptococcus pyogenes. The results reveal that alleles of the streptokinase gene have a mosaic structure, and provide strong evidence for intragenic recombination. Moreover, organisms that are well differentiated in overall chromosomal character have identical skn alleles, which suggests that horizontal gene transfer and recombination have participated in the evolution of this locus. No simple relationship between skn allele and serum opacity factor production or specific disease was identified. The predicted amino acid sequences of highly divergent skn alleles are strikingly similar in hydrophobicity and hydrophobicity profiles, distribution of amphipathic and flexible regions, surface probability plots, and antigenic indices, indicating that despite extensive nucleotide polymorphism in the two skn variable regions, selective pressure has constrained overall structural divergence. These results add to an important emerging theme that intragenic recombination plays a critical role in diversifying genes coding for streptococcal virulence factors.

Isolation by distance in a hierarchically clustered population

A biological population with local random mating, migration, and mutation is studied that exhibits clustering at several different levels. The migration is determined by the clustering rather than actual geographic or physical distance. Darwinian selection is assumed to be absent, and population densities are such that nearby individuals have a probability of being related. An expression is found for the equilibrium probability of genetic relatedness between any two individuals as a function of their clustering distance. Asymptotics for a small mutation rate u are discussed for both a finite number of clustering levels (and of total population size), and for an infinite number of levels. A natural example is discussed in which the probability of heterozygosity varies as u to a power times a periodic function of log(1/u).