On guarantee optimization in control problem with finite set of disturbances

In this paper, we deal with a control problem under conditions of disturbances, which is stated as a problem of optimization of the guaranteed result. Compared to the classical formulation of such problems, we assume that the set of admissible disturbances is finite and consists of piecewise continuous functions. In connection with this additional functional constraint on the disturbance, we introduce an appropriate class of non-anticipative control strategies and consider the corresponding value of the optimal guaranteed result. Under a technical assumption concerning a property of distinguishability of the admissible disturbances, we prove that this result can be achieved by using control strategies with full memory. As a consequence, we establish unimprovability of the class of full-memory strategies. A key element of the proof is a procedure of recovering the disturbance acting in the system, which allows us to associate every non-anticipative strategy with a full-memory strategy providing a close guaranteed result. The paper concludes with an illustrative example.

Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution

Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.

Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution

Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.

In the presence of population structure: From genomics to candidate genes underlying local adaptation

Understanding the genomic signatures, genes, and traits underlying local adaptation of organisms to heterogeneous environments is of central importance to the field evolutionary biology. Mixed linear mrsodels that identify allele associations to environment, while controlling for genome-wide variation at other loci, have emerged as the method of choice when studying local adaptation. Despite their importance, it is unclear whether this approach performs better than identifying environmentally-associated SNPs without accounting for population structure. To examine this, we first use the mixed linear model GEMMA, and simple Spearman correlations, to identify SNPs showing significant associations to climate with and without accounting for population structure. Subsequently, using Italy and Sweden populations, we compare evidence of allele frequency differentiation (FST), linkage disequilibrium (LD), fitness variation, and functional constraint, underlying these SNPs. Using a lenient cut-off for significance, we find that SNPs identified by both approaches, and SNPs uniquely identified by Spearman correlations, were enriched at sites showing genomic evidence of local adaptation and function but were limited across Quantitative Trait Loci (QTL) explaining fitness variation. SNPs uniquely identified by GEMMA, showed no direct or indirect evidence of local adaptation, and no enrichment along putative functional sites. Finally, SNPs that showed significantly high FST and LD, were enriched along fitness QTL peaks and cis-regulatory/nonsynonymous sites showing significant functional constraint. Using these SNPs, we identify genes underlying fitness QTL, and genes linking flowering time to local adaptation. These include a regulator of abscisic-acid (FLDH) and flowering time genes PIF3, FIO1, and COL5.

Sense-antisense gene overlap causes evolutionary retention of the few introns in Giardia genome and the implications

BackgroundIt is widely accepted that the last eukaryotic common ancestor (LECA) and early eukaryotes were intron-rich and intron loss dominated subsequent evolution, thus the presence of only very few introns in some modern eukaryotes must be the consequence of massive loss. But it is striking that few eukaryotes were found to have completely lost introns. Despite extensive research, the causes of massive intron losses remain elusive, and actually the reverse question – how the few introns are retained under the pressure of loss is equally significant but was rarely studied, except that it was conjectured that the essential functions of some introns prevent their loss. The extremely few (eight) spliceosome-mediated cis-spliced introns in the relatively simple genome of Giardia lamblia provide an excellent opportunity to explore this question.ResultsOur investigation of the intron-containing genes and introns in Giardia found three types of intron distribution patterns: ancient intron in ancient gene, relatively new intron in ancient gene, and relatively new intron in relatively new gene, which can reflect to some extent the dynamic evolution of introns in Giardia. Not finding any special features or functional importance of these introns responsible for the retention, we noticed and experimentally verified that some intron-containing genes form sense-antisense gene pairs with functional genes on their complementary strands, and that the introns just reside in the overlapping regions.ConclusionsIn Giardia’s evolution, despite constant pressure of intron loss, intron gain can still occur in both ancient and newly-evolved genes, but only a few introns have been retained; the evolutionary retention of introns is most likely not due to the functional constraint of the introns themselves but the causes outside of introns, such as the constraints imposed by other genomic functional elements overlapping with the introns. These findings can not only provide some clues to find new genomic functional elements -- in the areas overlapping with introngs, but suggest that “functional constraint” of introns may not be necessarily directly associated with intron loss and gain, or that the real functions or the way of functioning of introns are probably still outside of our current knowledge.