Lev Y. Yampolsky

Bias in the introduction of variation as an orienting factor in evolution

SUMMARY According to New Synthesis doctrine, the direction of evolution is determined by selection and not by “internal causes” that act by way of propensities of variation. This doctrine rests on the theoretical claim that because mutation rates are small in comparison to selection coefficients, mutation is powerless to overcome opposing selection. Using a simple population‐genetic model, this claim is shown to depend on assuming the prior availability of variation, so that mutation may act only as a “pressure” on the frequencies of existing alleles, and not as the evolutionary process that introduces novelty. As shown here, mutational bias in the introduction of novelty can strongly influence the course of evolution, even when mutation rates are small in comparison to selection coefficients. Recognizing this mode of causation provides a distinct mechanistic basis for an “internalist” approach to determining the contribution of mutational and developmental factors to evolutionary phenomena such as homoplasy, parallelism, and directionality.

Genetics of life history in Daphnia magna. I: Heritabilities at two food levels

Broad- and narrow-sense heritabilities for several life-history traits were estimated from 23 mother-daughter pairs of Daphnia magna at two food levels. Sexually produced daughter clones were obtained from a field collection of ephippial females (mothers) and the subsequent hatching of their ephippial eggs (daughters). Mother and daughter clones were maintained by parthenogenetic reproduction. Heritabilities of adult body-length of eight successive instars were the highest estimates of all in good food, but the lowest of all in poor food. For clutch size and body-length of offspring from the first six clutches, narrow- and broad-sense heritabilities were about equal and lower in poor food than in good food. The amount of genetic variation present would allow a response to selection on clutch size and offspring length in both environments but adult length only in good food. For age at maturity we found no additive genetic variance. We found no difference in broad-sense heritabilities between mother clones, representing the last generation after a period of asexual reproduction, and their sexually produced offspring. This suggests that genetic variance does not increase after one sexual generation or that it was not reduced before. Differences in heritabilities between environments are discussed with reference to the enlarged phenotypic variances that result from variation in juvenile instar number. Targeted growth could explain the pronounced differences in the heritabilities of adult length between environments.

Adaptive phenotypic plasticity and local adaptation for temperature tolerance in freshwater zooplankton

Many organisms have geographical distributions extending from the tropics to near polar regions or can experience up to 30°C temperature variation within the lifespan of an individual. Two forms of evolutionary adaptation to such wide ranges in ambient temperatures are frequently discussed: local adaptation and phenotypic plasticity. The freshwater planktonic crustacean Daphnia magna, whose range extends from South Africa to near arctic sites, shows strong phenotypic and genotypic variation in response to temperature. In this study, we use D. magna clones from 22 populations (one clone per population) ranging from latitude 0° (Kenya) to 66° North (White Sea) to explore the contributions of phenotypic plasticity and local adaptation to high temperature tolerance. Temperature tolerance was studied as knockout time (time until immobilization, Timm) at 37°C in clones acclimatized to either 20°C or 28°C. Acclimatization to 28°C strongly increased Timm, testifying to adaptive phenotypic plasticity. At the same time, Timm significantly correlated with average high temperature at the clones’ sites of origin, suggesting local adaptation. As earlier studies have found that haemoglobin expression contributes to temperature tolerance, we also quantified haemoglobin concentration in experimental animals and found that both acclimatization temperature (AccT) and temperature at the site of origin are positively correlated with haemoglobin concentration. Furthermore, Daphnia from warmer climates upregulate haemoglobin much more strongly in response to AccT, suggesting local adaptation for plasticity in haemoglobin expression. Our results show that both local adaptation and phenotypic plasticity contribute to temperature tolerance, and elucidate a possible role of haemoglobin in mediating these effects that differs along a cold–warm gradient.

Genetics of life history in Daphnia magna . II. Phenotypic plasticity

The phenotypic plasticities of life-history traits in 46 clones of the planktonic crustacean Daphnia magna were measured across two feeding conditions. Plasticity estimates for clutch sizes and offspring lengths of the first six clutches and for lengths of eight successive adult instars allowed us to compare plasticity between and within these three trait groups. Data were standardized (mean = 0, variance = 1) in each environment before analysis. The broad-sense heritability of plasticity of adult length increased from about 0 in the adolescent instar to 60 per cent in the 7th adult instar, while narrow-sense heritability was low for all instars. For clutch sizes, narrow- and broad-sense heritabilities were around 25 per cent. For offspring length, they were mostly close to zero. A comparison of three methods of quantifying plasticity showed that the heritabilities of trait differences across environments and the heritabilities based on genotype by environment interaction components were consistent with each other, but the later is always smaller. Cross-environment genetic correlations gave qualitatively different results.

Widespread Transcriptional Autosomal Dosage Compensation in Drosophila Correlates with Gene Expression Level

Little is known about dosage compensation in autosomal genes. Transcription-level compensation of deletions and other loss-of-function mutations may be a mechanism of dominance of wild-type alleles, a ubiquitous phenomenon whose nature has been a subject of a long debate. We measured gene expression in two isogenic Drosophila lines heterozygous for long deletions and compared our results with previously published gene expression data in a line heterozygous for a long duplication. We find that a majority of genes are at least partially compensated at transcription, both for ½-fold dosage (in heterozygotes for deletions) and for 1.5-fold dosage (in heterozygotes for a duplication). The degree of compensation does not vary among functional classes of genes. Compensation for deletions is stronger for highly expressed genes. In contrast, the degree of compensation for duplications is stronger for weakly expressed genes. Thus, partial transcriptional compensation appears to be based on regulatory mechanisms that insure high transcription levels of some genes and low transcription levels of other genes, instead of precise maintenance of a particular homeostatic expression level. Given the ubiquity of transcriptional compensation, dominance of wild-type alleles may be at least partially caused by of the regulation at transcription level.

Functional genomics of acclimation and adaptation in response to thermal stress in Daphnia

BackgroundGene expression regulation is one of the fundamental mechanisms of phenotypic plasticity and is expected to respond to selection in conditions favoring phenotypic response. The observation that many organisms increase their stress tolerance after acclimation to moderate levels of stress is an example of plasticity which has been long hypothesized to be based on adaptive changes in gene expression. We report genome-wide patterns of gene expression in two heat-tolerant and two heat-sensitive parthenogenetic clones of the zooplankton crustacean Daphnia pulex exposed for three generations to either optimal (18°C) or substressful (28°C) temperature.ResultsA large number of genes responded to temperature and many demonstrated a significant genotype-by-environment (GxE) interaction. Among genes with a significant GxE there were approximately equally frequent instances of canalization, i.e. stronger plasticity in heat-sensitive than in heat-tolerant clones, and of enhancement of plasticity along the evolutionary vector toward heat tolerance. The strongest response observed is the across-the-board down-regulation of a variety of genes occurring in heat-tolerant, but not in heat-sensitive clones. This response is particularly obvious among genes involved in core metabolic pathways and those responsible for transcription, translation and DNA repair.ConclusionsThe observed down-regulation of metabolism, consistent with previous findings in yeast and Drosophila, may reflect a general compensatory stress response. The associated down-regulation of DNA repair pathways potentially creates a trade-off between short-term benefits of survival at high temperature and long-term costs of accelerated mutation accumulation.

Variation and plasticity of biomass allocation in Daphnia

1. For organisms with indeterminate growth a trade-off between growth and reproduction is expected. The detection of this trade-off depends not only on the covariance between these two traits, but also on the variation of their sum, the total production (TP = growth + reproduction). The smaller the relative variation in TP, the more likely it is to detect the trade-off. To investigate this trade-off, we studied biomass allocation and variation of 56 clones of Daphnia magna from two populations under two food conditions. 2. Broad-sense heritabilities of clutch mass, growth, TP and the allocation ratio (R = clutch mass/TP) were higher in rich than in poor food conditions. Growth and R showed no genetic variation at the low food level

Amino Acid Exchangeability and the Adaptive Code Hypothesis

Since the genetic code first was determined, many have claimed that it is organized adaptively, so as to assign similar codons to similar amino acids. This claim has proved difficult to establish due to the absence of relevant comparative data on alternative primordial codes and of objective measures of amino acid exchangeability. Here we use a recently developed measure of exchangeability to evaluate a null hypothesis and two alternative hypotheses about the adaptiveness of the genetic code. The null hypothesis that there is no tendency for exchangeable amino acids to be assigned to similar codons can be excluded here as expected from earlier work. The first alternative hypothesis is that any such correlation between codon distance and amino acid distance is due to incremental mechanisms of code evolution, and not to adaptation to reduce deleterious effects of future mutations. More specifically, new codon assignments that occur by ambiguity reduction or by codon capture will tend to give rise to correlations, whether due to the condition of amino acid ambiguity, or to the condition of similarity between a new tRNA synthetase (or tRNA) and its parent. The second alternative hypothesis, the adaptive hypothesis, then may be defined as an excess relative to what may be expected given the incremental nature of evolution, reflecting true adaptation for robustness rather than an incidental effect. The results reported here indicate that most of the nonrandomness in the amino acids to codon assignments can be explained by incremental code evolution, with a small residue of orderliness that may reflect code adaptation.

Evolutionary patterns of amino acid substitutions in 12 Drosophila genomes.

BackgroundHarnessing vast amounts of genomic data in phylogenetic context stemming from massive sequencing of multiple closely related genomes requires new tools and approaches. We present a tool for the genome-wide analysis of frequencies and patterns of amino acid substitutions in multiple alignments of genes’ coding regions, and a database of amino acid substitutions in the phylogeny of 12 Drosophila genomes. We illustrate the use of these resources to address three types of evolutionary genomics questions: about fluxes in amino acid composition in proteins, about asymmetries in amino acid substitutions and about patterns of molecular evolution in duplicated genes.ResultsWe demonstrate that amino acid composition of Drosophila proteins underwent a significant shift over the last 70 million years encompassed by the studied phylogeny, with less common amino acids (Cys, Met, His) increasing in frequency and more common ones (Ala, Leu, Glu) becoming less frequent. These fluxes are strongly correlated with polarity of source and destination amino acids, resulting in overall systematic decrease of mean polarity of amino acids found in Drosophila proteins. Frequency and radicality of amino acid substitutions are higher in paralogs than in orthologous single-copy genes and are higher in gene families with paralogs than in gene families without surviving duplications. Rate and radicality of substitutions, as expected, are negatively correlated with overall level and uniformity of gene expression. However, these correlations are not observed for substitutions occurring in duplicated genes, indicating a different selective constraint on the evolution of paralogous sequences. Clades resulting from duplications show a marked asymmetry in rate and radicality of amino acid substitutions, possibly a signal of widespread neofunctionalization. These patterns differ among protein families of different functionality, with genes coding for RNA-binding proteins differing from most other functional groups in terms of amino acid substitution patterns in duplicated and single-copy genes.ConclusionsWe demonstrate that deep phylogenetic analysis of amino acid substitutions can reveal interesting genome-wide patterns. Amino acid composition of drosophilid proteins is shaped by fluxes similar to those previously observed in prokaryotic, yeast and mammalian genomes, indicating globally present patterns. Increased frequency and radicality of amino acid substitutions in duplicated genes and the presence of asymmetry of these parameters between paralogous clades indicate widespread neofunctionalization among paralogs as the mechanism of duplication retention.

Mentoring Interdisciplinary Undergraduate Students via a Team Effort

We describe how a team approach that we developed as a mentoring strategy can be used to recruit, advance, and guide students to be more interested in the interdisciplinary field of mathematical biology, and lead to success in undergraduate research in this field. Students are introduced to research in their first semester via lab rotations. Their participation in the research of four faculty members—two from biology and two from mathematics—gives them a first-hand overview of research in quantitative biology and also some initial experience in research itself. However, one of the primary goals of the lab rotation experience is that of developing teams of students and faculty that combine mathematics and statistics with biology and the life sciences, teams that subsequently mentor undergraduate research in genuine interdisciplinary environments. Thus, the team concept serves not only as a means of establishing interdisciplinary research, but also as a means of incorporating new students into existing research efforts that will then track those students into meaningful research of their own. We report how the team concept is used to support undergraduate research in mathematical biology and what types of team-building strategies have worked for us.