A mission to convert.
Primarily a review of Richard Dawkins' book, The God delusion (Boston: Houghton Mifflin, 2006).
Biological Evolution↗
Biomedical subjects
H Allen Orr
Publications and source records attributed to H Allen Orr.
Speciation in Drosophila: from phenotypes to molecules.
Study of the genetics of speciation--and especially of the genetics of intrinsic postzygotic isolation-has enjoyed remarkable progress over the last 2 decades. Indeed progress has been so rapid that one might be tempted to ask if the genetics of postzygotic isolation is now wrapped up. Here we argue that the genetics of speciation is far from complete. In particular, we review 2 topics where recent work has revealed major surprises: 1) the role of meiotic drive in hybrid sterility and 2) the role of gene transposition in speciation. These surprises, and others like them, suggest that evolutionary biologists may understand less about the genetic basis of speciation than seemed likely a few years ago.
Animals↗
Gene transposition as a cause of hybrid sterility in Drosophila.
We describe reproductive isolation caused by a gene transposition. In certain Drosophila melanogaster-D. simulans hybrids, hybrid male sterility is caused by the lack of a single-copy gene essential for male fertility, JYAlpha. This gene is located on the fourth chromosome of D. melanogaster but on the third chromosome of D. simulans. Genomic and molecular analyses show that JYAlpha transposed to the third chromosome during the evolutionary history of the D. simulans lineage. Because of this transposition, a fraction of hybrids completely lack JYAlpha and are sterile, representing reproductive isolation without sequence evolution.
Animals↗
The population genetics of adaptation on correlated fitness landscapes: the block model.
Several recent theoretical studies of the genetics of adaptation have focused on the mutational landscape model, which considers evolution on rugged fitness landscapes (i.e., ones having many local optima). Adaptation in this model is characterized by several simple results. Here I ask whether these results also hold on correlated fitness landscapes, which are smoother than those considered in the mutational landscape model. In particular, I study the genetics of adaptation in the block model, a tunably rugged model of fitness landscapes. Considering the scenario in which adaptation begins from a high fitness wild-type DNA sequence, I use extreme value theory and computer simulations to study both single adaptive steps and entire adaptive walks. I show that all previous results characterizing single steps in adaptation in the mutational landscape model hold at least approximately on correlated landscapes in the block model; many entire-walk results, however, do not.
Adaptation, Physiological↗
Adaptation in sexuals vs. asexuals: clonal interference and the Fisher-Muller model.
Fisher and Muller's theory that recombination speeds adaptation by eliminating competition among beneficial mutations has proved a popular explanation for the advantage of sex. Recent theoretical studies have attempted to quantify the speed of adaptation under the Fisher-Muller model, partly in an attempt to understand the role of "clonal interference" in microbial experimental evolution. We reexamine adaptation in sexuals vs. asexuals, using a model of DNA sequence evolution. In this model, a modest number of sites can mutate to beneficial alleles and the fitness effects of these mutations are unequal. We study (1) transition probabilities to different beneficial mutations; (2) waiting times to the first and the last substitutions of beneficial mutations; and (3) trajectories of mean fitness through time. We find that some of these statistics are surprisingly similar between sexuals and asexuals. These results highlight the importance of the choice of substitution model in assessing the Fisher-Muller advantage of sex.
Adaptation, Biological↗
The distribution of fitness effects among beneficial mutations in Fisher's geometric model of adaptation.
Recent models of adaptation at the DNA sequence level assume that the fitness effects of new mutations show certain statistical properties. In particular, these models assume that the distribution of fitness effects among new mutations is in the domain of attraction of the so-called Gumbel-type extreme value distribution. This assumption has not, however, been justified on any biological or theoretical grounds. In this note, I study random mutation in one of the simplest models of mutation and adaptation-Fisher's geometric model. I show that random mutation in this model yields a distribution of mutational effects that belongs to the Gumbel type. I also show that the distribution of fitness effects among rare beneficial mutations in Fisher's model is asymptotically exponential. I confirm these analytic findings with exact computer simulations. These results provide some support for the use of Gumbel-type extreme value theory in studies of adaptation and point to a surprising connection between recent phenotypic- and sequence-based models of adaptation: in both, the distribution of fitness effects among rare beneficial mutations is approximately exponential.
Adaptation, Physiological↗
The genetic basis of reproductive isolation: insights from Drosophila.
Recent studies of the genetics of speciation in Drosophila have focused on two problems: (i) identifying and characterizing the genes that cause reproductive isolation, and (ii) determining the evolutionary forces that drove the divergence of these "speciation genes." Here, I review this work. I conclude that speciation genes correspond to ordinary loci having normal functions within species. These genes fall into several functional classes, although a role in transcriptional regulation could prove particularly common. More important, speciation genes are typically very rapidly evolving, and this divergence is often driven by positive Darwinian selection. Finally, I review recent work in Drosophila pseudoobscura on the possible role of meiotic drive in the evolution of the genes that cause postzygotic isolation.
Animals↗
Segregation distortion in hybrids between the Bogota and USA subspecies of Drosophila pseudoobscura.
We show that, contrary to claims in the literature, "sterile" males resulting from the cross of the Bogota and USA subspecies of Drosophila pseudoobscura are weakly fertile. Surprisingly, these hybrid males produce almost all daughters when crossed to females of any genotype (pure Bogota, pure USA, hybrid F1). Several lines of evidence suggest that this sex ratio distortion is caused by sex chromosome segregation distortion in hybrid males. We genetically analyze this normally cryptic segregation distortion and show that it involves several regions of the Bogota X chromosome that show strong epistatic interactions with each other. We further show that segregation distortion is normally masked within the Bogota subspecies by autosomal suppressors. Our analysis shows that the genetic basis of hybrid segregation distortion is similar to that of hybrid male sterility between the same subspecies. Indeed the severity of segregation distortion is correlated with the severity of sterility among hybrids. We discuss the possibility that hybrid sterility in this paradigmatic case of incipient speciation is caused by segregation distortion.
Animals↗
Theories of adaptation: what they do and don't say.
Theoretical work on adaptation has lagged behind experimental. But two classes of adaptation model have been partly explored. One is phenotypic and the other DNA sequence based. I briefly consider an example of each--Fisher's geometric model and Gillespie's mutational landscape model, respectively--reviewing recent results. Despite their fundamental differences, these models give rise to several strikingly similar results. I consider possible reasons for this congruence. I also emphasize what predictions do and, as important, do not follow from these models.
Adaptation, Biological↗
The genetic theory of adaptation: a brief history.
Theoretical studies of adaptation have exploded over the past decade. This work has been inspired by recent, surprising findings in the experimental study of adaptation. For example, morphological evolution sometimes involves a modest number of genetic changes, with some individual changes having a large effect on the phenotype or fitness. Here I survey the history of adaptation theory, focusing on the rise and fall of various views over the past century and the reasons for the slow development of a mature theory of adaptation. I also discuss the challenges that face contemporary theories of adaptation.
Adaptation, Biological↗
The probability of parallel evolution.
How often will natural selection drive parallel evolution at the DNA sequence level? More precisely, what is the probability that selection will cause two populations that live in identical environments to substitute the same beneficial mutation? Here I show that, under fairly general conditions, the answer is simple: if a wild-type sequence can mutate to n different beneficial mutations, replicate populations will on average fix the same mutation with probability P = 2/(n + 1). This probability, which is derived using extreme value theory, is independent of most biological details, including the length of the gene in question and the precise distribution of fitness effects among alleles. I conclude that the probability of parallel evolution under natural selection is nearly twice as large as that under neutrality.
Adaptation, Biological↗
Speciation genes.
Until recently, the genes that cause reproductive isolation remained black boxes. Consequently, evolutionary biologists were unable to answer several questions about the identities and characteristics of "speciation genes". Over the past few years, however, evolutionary geneticists have finally succeeded in isolating several such genes, providing our first glimpse at factors that are thought to be representative of those underlying the origin of species. Evolutionary analysis of these genes suggests that speciation results from positive Darwinian selection within species. Molecular evolutionary study of the genes causing reproductive isolation may represent an important new phase in the study of speciation.
Animals↗
A pseudohitchhiking model of X vs. autosomal diversity.
We study levels of X-linked vs. autosomal diversity using a model developed to analyze the hitchhiking effect. Repeated bouts of hitchhiking are thought to lower X-linked diversity for two reasons: first, because sojourn times of beneficial mutations are shorter on the X, and second, because adaptive substitutions may be more frequent on the X. We investigate whether each of these effects does, in fact, cause reduced X-linked diversity under hitchhiking. We study the strength of the hitchhiking effect on the X vs. autosomes when there is no recombination and under two different recombination schemes. When recombination occurs in both sexes, X-linked vs. autosomal diversity is reduced by hitchhiking under a broad range of conditions, but when there is no recombination in males, as in Drosophila, the required conditions are considerably more restrictive.
Animals↗
Adaptive evolution drives divergence of a hybrid inviability gene between two species of Drosophila.
Speciation--the splitting of one species into two--occurs by the evolution of any of several forms of reproductive isolation between taxa, including the intrinsic sterility and inviability of hybrids. Abundant evidence shows that these hybrid fitness problems are caused by incompatible interactions between loci: new alleles that become established in one species are sometimes functionally incompatible with alleles at interacting loci from another species. However, almost nothing is known about the genes involved in such hybrid incompatibilities or the evolutionary forces that drive their divergence. Here we identify a gene that causes epistatic inviability in hybrids between two fruitfly species, Drosophila melanogaster and D. simulans. Our population genetic analysis reveals that this gene--which encodes a nuclear pore protein--evolved by positive natural selection in both species' lineages. These results show that a lethal hybrid incompatibility has evolved as a by-product of adaptive protein evolution.
Adaptation, Biological↗
A minimum on the mean number of steps taken in adaptive walks.
I consider the adaptation of a DNA sequence when mutant fitnesses are drawn randomly from a probability distribution. I focus on "gradient" adaptation in which the population jumps to the best mutant sequence available at each substitution. Given a random starting point, I derive the distribution of the number of substitutions that occur during adaptive walks to a locally optimal sequence. I show that the mean walk length is a constant:L = e-1, where e approximately 2.72. I argue that this result represents a limit on what is possible under any form of adaptation. No adaptive algorithm on any fitness landscape can arrive at a local optimum in fewer than a mean of L = e-1 steps when starting from a random sequence. Put differently, evolution must try out at least e wild-type sequences during an average bout of adaptation.
Adaptation, Biological↗
The distribution of fitness effects among beneficial mutations.
We know little about the distribution of fitness effects among new beneficial mutations, a problem that partly reflects the rarity of these changes. Surprisingly, though, population genetic theory allows us to predict what this distribution should look like under fairly general assumptions. Using extreme value theory, I derive this distribution and show that it has two unexpected properties. First, the distribution of beneficial fitness effects at a gene is exponential. Second, the distribution of beneficial effects at a gene has the same mean regardless of the fitness of the present wild-type allele. Adaptation from new mutations is thus characterized by a kind of invariance: natural selection chooses from the same spectrum of beneficial effects at a locus independent of the fitness rank of the present wild type. I show that these findings are reasonably robust to deviations from several assumptions. I further show that one can back calculate the mean size of new beneficial mutations from the observed mean size of fixed beneficial mutations.
Data Interpretation, Statistical↗
The population genetics of adaptation: the adaptation of DNA sequences.
I describe several patterns characterizing the genetics of adaptation at the DNA level. Following Gillespie (1983, 1984, 1991), I consider a population presently fixed for the ith best allele at a locus and study the sequential substitution of favorable mutations that results in fixation of the fittest DNA sequence locally available. Given a wild type sequence that is less than optimal, I derive the fitness rank of the next allele typically fixed by natural selection as well as the mean and variance of the jump in fitness that results when natural selection drives a substitution. Looking over the whole series of substitutions required to reach the best allele, I show that the mean fitness jumps occurring throughout an adaptive walk are constrained to a twofold window of values, assuming only that adaptation begins from a reasonably fit allele. I also show that the first substitution and the substitution of largest effect account for a large share of the total fitness increase during adaptation. I further show that the distribution of selection coefficients fixed throughout such an adaptive walk is exponential (ignoring mutations of small effect), a finding reminiscent of that seen in Fisher's geometric model of adaptation. Last, I show that adaptation by natural selection behaves in several respects as the average of two idealized forms of adaptation, perfect and random.
Adaptation, Physiological↗
The genetics of species differences.
Species are separated by reproductive isolation as well as by more 'ordinary' differences in morphology and behavior that play no necessary role in blocking gene flow. Although a great deal is now known about the genetics of reproductive isolation, we are only beginning to understand the genetic basis of ordinary phenotypic differences between species. I review what is known about the number of genes involved in such differences, as well as about the role of major genes and epistasis in the evolution of these differences. I also compare and contrast these findings with those on the genetics of reproductive isolation.
Journal Article↗