Jon F. Wilkins

What good is genomic imprinting: the function of parent-specific gene expression.

Parent-specific gene expression (genomic imprinting) is an evolutionary puzzle because it forgoes an important advantage of diploidy — protection against the effects of deleterious recessive mutations. Three hypotheses claim to have found a countervailing selective advantage of parent-specific expression. Imprinting is proposed to have evolved because it enhances evolvability in a changing environment, protects females against the ravages of invasive trophoblast, or because natural selection acts differently on genes of maternal and paternal origin in interactions among kin. The last hypothesis has received the most extensive theoretical development and seems the best supported by the properties of known imprinted genes. However, the hypothesis is yet to provide a compelling explanation for many examples of imprinting.

Detecting Regular Sound Changes in Linguistics as Events of Concerted Evolution

Summary Background Concerted evolution is normally used to describe parallel changes at different sites in a genome, but it is also observed in languages where a specific phoneme changes to the same other phoneme in many words in the lexicon—a phenomenon known as regular sound change. We develop a general statistical model that can detect concerted changes in aligned sequence data and apply it to study regular sound changes in the Turkic language family. Results Linguistic evolution, unlike the genetic substitutional process, is dominated by events of concerted evolutionary change. Our model identified more than 70 historical events of regular sound change that occurred throughout the evolution of the Turkic language family, while simultaneously inferring a dated phylogenetic tree. Including regular sound changes yielded an approximately 4-fold improvement in the characterization of linguistic change over a simpler model of sporadic change, improved phylogenetic inference, and returned more reliable and plausible dates for events on the phylogenies. The historical timings of the concerted changes closely follow a Poisson process model, and the sound transition networks derived from our model mirror linguistic expectations. Conclusions We demonstrate that a model with no prior knowledge of complex concerted or regular changes can nevertheless infer the historical timings and genealogical placements of events of concerted change from the signals left in contemporary data. Our model can be applied wherever discrete elements—such as genes, words, cultural trends, technologies, or morphological traits—can change in parallel within an organism or other evolving group.

Genomic imprinting of two antagonistic loci

We present a model that considers the coevolution of genomic imprinting at a growth factor locus and an antagonistic growth suppressor locus. With respect to the two loci considered independently, our model makes the familiar predictions that an imprinted growth factor locus will only be expressed from the paternally derived allele and an imprinted growth suppressor locus only from the maternally derived allele. In addition, our coevolutionary model allows us to make predictions regarding the sequence of evolutionary events necessary for generating such a system. We conclude that imprinting at the growth factor locus preceded the evolution of growth suppressor function at the second locus, which in turn preceded imprinting at that locus. We then discuss the consistency of these predictions with currently available comparative data on the insulin-like growth factor 2 —insulin–like growth factor 2 receptor system of mammals.

The Red Queen theory of recombination hotspots

Recombination hotspots are small chromosomal regions, where meiotic crossover events happen with high frequency. Recombination is initiated by a double‐strand break (DSB) that requires the intervention of the molecular repair mechanism. The DSB repair mechanism may result in the exchange of homologous chromosomes (crossover) and the conversion of the allelic sequence that breaks into the one that does not break (biased gene conversion). Biased gene conversion results in a transmission advantage for the allele that does not break, thus preventing recombination and rendering recombination hotspots transient. How is it possible that recombination hotspots persist over evolutionary time (maintaining the average chromosomal crossover rate) when they are self‐destructive? This fundamental question is known as the recombination hotspot paradox and has attracted much attention in recent years. Yet, that attention has not translated into a fully satisfactory answer. No existing model adequately explains all aspects of the recombination hotspot paradox. Here, we formulate an intragenomic conflict model resulting in Red Queen dynamics that fully accounts for all empirical observations regarding the molecular mechanisms of recombination hotspots, the nonrandom targeting of the recombination machinery to hotspots and the evolutionary dynamics of hotspot turnover.

Parental modifiers, antisense transcripts and loss of imprinting

The kinship theory of genomic imprinting has explained parent–specific gene expression as the outcome of an evolutionary conflict between the two alleles at a diploid locus of an offspring over how much to demand from parents. Previous models have predicted that maternally derived (madumnal) alleles will be silent at demand–enhancing loci, while paternally derived (padumnal) alleles will be silent at demand–suppressing loci, but these models have not considered the evolution of trans–acting modifiers that are expressed in parents and influence imprinted expression in offspring. We show that such modifiers will sometimes be selected to reactivate the silent padumnal allele at a demand–suppressing locus but will not be selected to reactivate the silent madumnal allele at a demand–enhancing locus. Therefore, imprinting of demand–suppressing loci is predicted to be less evolutionarily stable than imprinting of demand–enhancing loci.

Demography, kinship, and the evolving theory of genomic imprinting

Genomic imprinting is the differential expression of an allele based on the parent of origin. Recent transcriptome-wide evaluations of the number of imprinted genes reveal complex patterns of imprinted expression among developmental stages and cell types. Such data demand a comprehensive evolutionary framework in which to understand the effect of natural selection on imprinted gene expression. We present such a framework for how asymmetries in demographic parameters and fitness effects can lead to the evolution of genomic imprinting and place recent theoretical advances in this framework. This represents a modern interpretation of the kinship theory, is well suited to studying populations with complex social interactions, and provides predictions which can be tested with forthcoming transcriptomic data. To understand the intricate phenotypic patterns that are emerging from the recent deluge of data, future investigations of genomic imprinting will require integrating evolutionary theory, transcriptomic data, developmental and functional genetics, and natural history.

On the universal structure of human lexical semantics

Significance Semantics, or meaning expressed through language, provides indirect access to an underlying level of conceptual structure. To what degree this conceptual structure is universal or is due to properties of cultural histories, or to the environment inhabited by a speech community, is still controversial. Meaning is notoriously difficult to measure, let alone parameterize, for quantitative comparative studies. Using cross-linguistic dictionaries across languages carefully selected as an unbiased sample reflecting the diversity of human languages, we provide an empirical measure of semantic relatedness between concepts. Our analysis uncovers a universal structure underlying the sampled vocabulary across language groups independent of their phylogenetic relations, their speakers’ culture, and geographic environment. How universal is human conceptual structure? The way concepts are organized in the human brain may reflect distinct features of cultural, historical, and environmental background in addition to properties universal to human cognition. Semantics, or meaning expressed through language, provides indirect access to the underlying conceptual structure, but meaning is notoriously difficult to measure, let alone parameterize. Here, we provide an empirical measure of semantic proximity between concepts using cross-linguistic dictionaries to translate words to and from languages carefully selected to be representative of worldwide diversity. These translations reveal cases where a particular language uses a single “polysemous” word to express multiple concepts that another language represents using distinct words. We use the frequency of such polysemies linking two concepts as a measure of their semantic proximity and represent the pattern of these linkages by a weighted network. This network is highly structured: Certain concepts are far more prone to polysemy than others, and naturally interpretable clusters of closely related concepts emerge. Statistical analysis of the polysemies observed in a subset of the basic vocabulary shows that these structural properties are consistent across different language groups, and largely independent of geography, environment, and the presence or absence of a literary tradition. The methods developed here can be applied to any semantic domain to reveal the extent to which its conceptual structure is, similarly, a universal attribute of human cognition and language use.

ANTAGONISTIC COEVOLUTION OF TWO IMPRINTED LOCI WITH PLEIOTROPIC EFFECTS

At a locus subject to genomic imprinting, the expression pattern of an allele depends on its parent of origin. Typically, one allele is expressed while the other is transcriptionally silent, and natural selection at the locus will be driven by the inclusive fitness of the active allele. For some aspects of phenotype, the relevant fitness function differs between maternally and paternally derived alleles, so that maternally and paternally expressed imprinted loci become involved in an intragenomic, interlocus conflict. Here I consider the consequences of such a conflict between loci with pleiotropic effects and show that phenotypes are driven away from their optimal values, resulting in a maladaptive, but selectively favored, evolutionary trajectory. The extent to which the evolutionarily stable state departs from the optimal phenotype depends only linearly on the magnitude of the conflict, but is extremely sensitive to the relationship between the pleiotropic effects of the two loci. Thus, even a small intragenomic conflict can have significant deleterious consequences for multiple aspects of phenotype. This result has potential consequences for our understanding of disease states that occur at high frequency in the population, including several common psychological and behavioral disorders such as schizophrenia, bipolar disorder, major depression, and autism.

The evolving landscape of imprinted genes in humans and mice: Conflict among alleles, genes, tissues, and kin

Three recent genome-wide studies in mice and humans have produced the most definitive map to date of genomic imprinting (gene expression that depends on parental origin) by incorporating multiple tissue types and developmental stages. Here, we explore the results of these studies in light of the kinship theory of genomic imprinting, which predicts that imprinting evolves due to differential genetic relatedness between maternal and paternal relatives. The studies produce a list of imprinted genes with around 120-180 in mice and ~100 in humans. The studies agree on broad patterns across mice and humans including the complex patterns of imprinted expression at loci like Igf2 and Grb10. We discuss how the kinship theory provides a powerful framework for hypotheses that can explain these patterns. Finally, since imprinting is rare in the genome despite predictions from the kinship theory that it might be common, we discuss evolutionary factors that could favor biallelic expression.

Genomic imprinting and conflict-induced decanalization.

Genomic imprinting is the phenomenon in which the expression pattern of an allele depends on its parental origin. When maternally expressed and paternally expressed imprinted loci affect the same trait, the result is an arms race, with each locus under selection to increase its level of expression. This article develops a model of the deleterious consequences of this escalation, deriving from an increase in the variance in gene expression level, and resulting increase in phenotypic variance in the population. This phenomenon is referred to here as “conflict‐induced decanalization.” Modifiers that canalize gene expression are selectively favored, but these induce further escalation from both loci, resulting in a net increase in phenotypic variance and a reduction in population mean fitness. This results in a feedback loop, where increasing canalization of gene expression leads to increasing decanalization of the phenotype. This phenomenon may explain the surprisingly high frequency of certain diseases. Disorders to which this decanalization process might contribute include growth‐ and metabolism‐related phenomena such as preterm birth, as well as certain major psychiatric disorders, including schizophrenia and autism.