On the role of metaheuristic optimization in bioinformatics

Metaheuristic algorithms are employed to solve complex and large-scale optimization problems in many different fields, from transportation and smart cities to finance. This paper discusses how metaheuristic algorithms are being applied to solve different optimization problems in the area of bioinformatics. While the text provides references to many optimization problems in the area, it focuses on those that have attracted more interest from the optimization community. Among the problems analyzed, the paper discusses in more detail the molecular docking problem, the protein structure prediction, phylogenetic inference, and different string problems. In addition, references to other relevant optimization problems are also given, including those related to medical imaging or gene selection for classification. From the previous analysis, the paper generates insights on research opportunities for the Operations Research and Computer Science communities in the field of bioinformatics

The roles of divergence and hybridization in shaping patterns of genetic and phenotypic variation across the evolutionary continuum in Juniperus and Piper

Genetic and phenotypic variation across populations, species, and radiations mediates the form and outcome of biotic and abiotic interactions and represents a major axis of biodiversity. Resolving patterns of variation across shallow and deep evolutionary divergences can provide key insights into the processes that generate and maintain this variation over micro- and macroevolutionary timescales. Additionally, variation in functional traits that interface with the biotic and abiotic environments plays an important role in adaptive evolution, and can shed light on the drivers of differentiation and diversification. Here, I analyzed genome-scale variation spanning individuals, populations, and species to 1) resolve complex diversification histories, 2) characterize landscape patterns of hybrid admixture and plant secondary chemistry, and 3) characterize macroevolutionary patterns of plant secondary chemistry. First, I reconstructed the evolutionary history of the serrate juniper clade of North America (Juniperus) as it diversified into arid habitats of the western United States and Mexico. Second, I examined how admixture across the species boundary influences patterns of genetic and phytochemical variation following secondary contact among three serrate juniper species. Finally, I resolve the timing and tempo of diversification in the Radula clade of Piper to understand how secondary chemistry evolves within a diverse tropical plant radiation. My work demonstrates the importance of evolutionary processes occurring along the evolutionary continuum for generating contemporary patterns of variation and diversity

Alfaviiruse nsP2 valk biokeemilisest vaatekohast: lugu mitmedomäänse valgu ensümaatilisest analüüsist

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Chikungunya viirus (CHIKV) on suure meditsiinilise tähtsusega viirus mis kuulub alfaviiruste perekonda sugukonnas Togaviridae. Pregusel ajal ei ole CHIKV vastast vaktsiini ega spetsiifilist ravi. CHIKV paljunemine nakatatud rakkudes sõltub tema RNA genoomilt sünteesitavatest replikaasi valkudest. NsP2 on nelja replikaasi valgu seas suurim ja tal on palju teadaolevaid või eeldatavaid aktiivsuseid. Käesolevas töös näidati eksperimentaalselt, et CHIKV nsP2 omab kaheahelalist RNAd lahtiharutavat aktiivsust ning võib läbi viia ka vastupidist protsessi – soodustada kaheahelalise RNA moodustamist. Mõlemad need funktsioonid on olemas ainult täispikal nsP2 valgul. Peale selle näidati, et nsP2 omab ka NTPaset ja proteaaset aktiivsust. Kuna ka need aktiivsused on kõige tugevamad täispikal valgul siis saab saadud tulemustest järeldada, et CHIKV nsP2 toimib kui üks tervik: valgu erinevad osad seonduvad omavahel ja mõjutavad vastastikku üksteise aktiivsusi. Lisaks sellele leiti, et nsP2 aktiivsuseid mõjutavad ka mutatsioonid, mis on seotud mitte-tsütotoksilise fenotüübiga st. viiruse võimetusega maha suruda raku biosünteese ja põhjustada raku surma. Siiski ei saa kogutud andmeist teha järeldust milline või millised defektid nsP2 funktsioonides seda fenotüüpi põhjustavad. Lisaks nsP2 funktsionaalsele analüüsile viidi läbi ka muude CHIKV replikaasi valkude ekspresserimine ja puhastamine. Saadud kõrge kvaliteediga valke kasutati efektiivsete polüklonaalsete antiseerumite saamiseks. Nüüdseks on need töövahedid kasutusel paljudes laborites üle maailma ja on võimaldanud välja selgitada palju uusi fakte CHIKV (ja alfaviiruste üldse) molekulaarbioloogia kohta.Chikungunya virus (CHIKV, genus Alphavirus, family Togaviridae) has a positive sense RNA genome with length approximately 12 kb. It codes for four nonstructural (ns) proteins designated as nsP1, nsP2, nsP3 and nsP4 and for five or six structural proteins. Ns-proteins are involved in replication of virus RNA, in addition they also have functions unrelated to RNA replication. Out of all the nsPs, nsP2 plays a pivotal role towards regulation of CHIKV RNA replication. The protein was known to have NTPase, RTPase and protease activity and its N-terminal region was presumed to have helicase activity. Out of the enzymatic activities of nsP2 the helicase related functionalities were most insufficiently studied. Further, it was not known why two different and seemingly disconnected functional entities such as protease and helicase are present on a single polypeptide and what could be the importance of N terminal most part of nsP2 on the helicase activity. The bioinformatical, biochemical and biophysical approaches were employed to characterize the helicase related activities and to reveal the apparent minimal requirements for these activities. The bioinformatics platform suggests that the 3D-structure of the first 470 aa of nsP2 resembles the fold pattern of ToMV helicase which is a superfamily 1 of helicase. In particular, this fragment was predicted to consist from three domains. From these the extreme N terminal domain appears to be disordered while the other two domains possess RecA-like fold which is commonly found in NTPases. The biochemical analysis, carried out with purified full length and manipulated versions of nsP2, revealed that the C-terminal part of nsP2, which was known to have protease activity, is also essential for RNA helicase activity. Thus, the presence of protease region in nsP2 is clearly not accidental and these different functional domains are co-evolved to accomplish more significant tasks. The use of biophysical method (CD spectroscopy) confirmed that secondary structures of wt and manipulated versions of nsP2 are comparable; this indicates that functional defects detected in various enzymatic activities did not result from misfolding of mutant proteins. This also applies to forms of nsP2 which were engineered to contain mutations associated with noncytotoxic (NCT) phenotype of CHIKV replicons. It was found, all analyzed nsP2 enzymatic activities (protease, NTPase and helicase activities) were invariably affected by the NCT related mutations. In general, however, there was no significant correlation observed between extent of enzymatic defect(s) of nsP2 and phenotype of corresponding replicon. Thus, the development of NCT phenotype is apparently more complicated and could involve a number of underneath viral replication related functionalities. Finally, a number of ns-proteins from different alphaviruses were expressed, purified to raise polyclonal sera. These represent tools for detection of viral proteins using different immunological, such as western blot and immunofluorescence, methods. Similarly, the standardized enzymatic assays of nsP2 represent platform for screening and analysis of potential inhibitors of CHIKV infection. Taken together, these works elevated general understanding of nsP2 from a biochemical perspective and provided useful tools for studies aiming to understand molecular biology of alphaviruses

Population Structure, Connectivity, and Phylogeography of Two Balistidae with High Potential for Larval Dispersal: \u3ci\u3eBalistes capriscus\u3c/i\u3e and \u3ci\u3eBalistes vetula\u3c/i\u3e

The gray triggerfish (Balistes capriscus) and the queen triggerfish (Balistes vetula) are two exploited reef fish distributed in tropical and temperate shelf waters of the Atlantic Ocean and the Mediterranean Sea. Both species are highly sedentary as adults but disperse pelagic larvae for extended periods of time potentially allowing connectivity across long distances under the action of oceanic currents. In this work population structure, phylogeography, and migration patterns were examined in the two species and contrasted with predictions of larval transport based on surface circulation data. A total of 1,017 gray triggerfish from twelve sampling localities spanning the species distribution range were assayed at 17 homologous microsatellite markers and sequence variation at the ND4 mitochondrial gene. Four genetically distinct populations were detected including (i) a North Atlantic group that comprised the North American, European, and Northwest African populations, (ii) a Mediterranean group that was inferred to result from a recent colonization of the Mediterranean Sea by a small number of migrants of North Atlantic origin, (iii) a southeastern Atlantic group that included populations from the Gulf of Guinea and Southwest Africa, and (iv) a southwestern Atlantic group recently diverged from the southeastern group. Analysis of phylogeography supported long-term historical isolation of the South Atlantic and North Atlantic groups. Assignment tests and isolation-by-distance analysis supported the hypothesis of long-distance connectivity with evidence for transatlantic migrations and estimates of the mean dispersal distance of 740 km or greater. The high estimates of contemporaneous migration rates (up to 36.7%) may reflect increased larval transport in connection with the recent development of new Sargassum in the equatorial region. Analysis of high density genome scans revealed homogeneous distributions of genetic variants among queen triggerfish from the French Antilles, the U.S. Virgin-Islands, and South Florida, suggesting high connectivity is occurring across the region. These findings suggest that, in both species, local recruitment depends largely on the output of spawning populations located hundreds or thousands of kilometers away from a given stock, highlighting the need to conserve populations across each species’ range in particular in areas where circulation patterns predict a low likelihood of incoming migrants

The role of visual adaptation in cichlid fish speciation

D. Shane Wright (1) , Ole Seehausen (2), Ton G.G. Groothuis (1), Martine E. Maan (1) (1) University of Groningen; GELIFES; EGDB(2) Department of Fish Ecology & Evolution, EAWAG Centre for Ecology, Evolution and Biogeochemistry, Kastanienbaum AND Institute of Ecology and Evolution, Aquatic Ecology, University of Bern.In less than 15,000 years, Lake Victoria cichlid fishes have radiated into as many as 500 different species. Ecological and sexual sel ection are thought to contribute to this ongoing speciation process, but genetic differentiation remains low. However, recent work in visual pigment genes, opsins, has shown more diversity. Unlike neighboring Lakes Malawi and Tanganyika, Lake Victoria is highly turbid, resulting in a long wavelength shift in the light spectrum with increasing depth, providing an environmental gradient for exploring divergent coevolution in sensory systems and colour signals via sensory drive. Pundamilia pundamila and Pundamilia nyererei are two sympatric species found at rocky islands across southern portions of Lake Victoria, differing in male colouration and the depth they reside. Previous work has shown species differentiation in colour discrimination, corresponding to divergent female preferences for conspecific male colouration. A mechanistic link between colour vision and preference would provide a rapid route to reproductive isolation between divergently adapting populations. This link is tested by experimental manip ulation of colour vision - raising both species and their hybrids under light conditions mimicking shallow and deep habitats. We quantify the expression of retinal opsins and test behaviours important for speciation: mate choice, habitat preference, and fo raging performance

Applied phylogeography : mapping the genetic resource of Honeybush across the Cape Floristic Region

Aim: Honeybush tea is a herbal infusion made from members of the Cape Floristic Region (CFR) endemic Cyclopia Vent. Consting of 21 extant species, six are anthropogenically redistributed across the CFR for Honeybush cultivation. However, with no information regarding the distribution and levels of genetic diversity among wild Honeybush populations, anthropogenic translocation of cultivated genotypes may risk disrupting natural genetic diversity patterns. In this thesis, an applied phylogeographic approach is used to provide baseline insights into the spatial structuring of Honeybush genetic diversity. Location: The Cape Floristic Region (CFR), located along the southern Cape of South Africa. Methods: Spatial structuring of evolutionary lineages within Cyclopia are explored at a genus level using data generated from the combination of Anchored Hybrid Enrichment library preparation and high through put sequencing. A High Resolution Melt analysis (HRM) toolkit is then developed to screen haplotype variation across three non-coding chloroplast loci. This HRM toolkit coupled with haplotype confirmation Sanger sequencing is then applied to describe the spatial structuring of genetic diversity in wild populations for two Honeybush species (C. intermedia and C. subternata) and to compare genetic diversity among wild and cultivated populations of three Honeybush species (C. intermedia, C. subternata, and C. longifolia). A reanalysis of published phylogeographic data focusing on CFR plant taxa is used to test if phylogeographic breaks occur across the boundaries among adjacent Centers of Endemism (CoEs). Finally, the low-copy nuclear data set generated via AHE and high throughput sequencing is summarized. Results: Phylogeographic structuring was detected at the inter- and intraspecific levels in Cyclopia. The genus level analysis revealed a strong phylogenetic split between western CFR and eastern CFR endemic species in the nuclear and chloroplast genomes. At the intraspecific level, HRM proved to be a high throughput and accurate tool for haplotype detection, revealing phylogeographic structuring of genetic diversity in C.intermediaand C.subternata. This genetic diversity and structuring was not detected in cultivated Honeybush populations, which appear to have originated from a small number of founding individuals and have experienced a genetic bottleneck. Spatial structuring of genetic lineages is common among CFR plant taxa and the reanalysis of existing data found a significant trend for phylogeographic breaks tooccuracrosstheboundariesamongadjacentCoEs. Finally, over200000baseswere sequenced across 445 low-copy nuclear loci for 14 Cyclopia species. Conclusions: This thesis provides important baseline information on the spatial distribution of wild Honeybush genetic diversity. Phylogeographic structuring is present in wild Honeybush populations. This however is not accounted for in cultivated populations, which may place wild genetic diversity at risk of being disrupted if geneflow among wild and cultivated populations occurs. The results from this thesis should therefore be used to develop precautionary guidelines for the anthropogenic redistribution of Honeybush genetic material for cultivation. Furthermore, the novel insights into regional patterns of phylogeohraphic structuring of plant populations should encourage more efficient and hypothesis driven sampling designs in future phylogeographic work in the CFR. The high throughput sequence data generated in this thesis should transform Cyclopia to a model organism for the study of molecular evolution in the CFR