Rate and cost of adaptation in the Drosophila Genome

Recent studies have consistently inferred high rates of adaptive molecular evolution between Drosophila species. At the same time, the Drosophila genome evolves under different rates of recombination, which results in partial genetic linkage between alleles at neighboring genomic loci. Here we analyze how linkage correlations affect adaptive evolution. We develop a new inference method for adaptation that takes into account the effect on an allele at a focal site caused by neighboring deleterious alleles (background selection) and by neighboring adaptive substitutions (hitchhiking). Using complete genome sequence data and fine-scale recombination maps, we infer a highly heterogeneous scenario of adaptation in Drosophila. In high-recombining regions, about 50% of all amino acid substitutions are adaptive, together with about 20% of all substitutions in proximal intergenic regions. In low-recombining regions, only a small fraction of the amino acid substitutions are adaptive, while hitchhiking accounts for the majority of these changes. Hitchhiking of deleterious alleles generates a substantial collateral cost of adaptation, leading to a fitness decline of about 30/2N per gene and per million years in the lowest-recombining regions. Our results show how recombination shapes rate and efficacy of the adaptive dynamics in eukaryotic genomes

The asexual genome of Drosophila

The rate of recombination affects the mode of molecular evolution. In high-recombining sequence, the targets of selection are individual genetic loci; under low recombination, selection collectively acts on large, genetically linked genomic segments. Selection under linkage can induce clonal interference, a specific mode of evolution by competition of genetic clades within a population. This mode is well known in asexually evolving microbes, but has not been traced systematically in an obligate sexual organism. Here we show that the Drosophila genome is partitioned into two modes of evolution: a local interference regime with limited effects of genetic linkage, and an interference condensate with clonal competition. We map these modes by differences in mutation frequency spectra, and we show that the transition between them occurs at a threshold recombination rate that is predictable from genomic summary statistics. We find the interference condensate in segments of low-recombining sequence that are located primarily in chromosomal regions flanking the centromeres and cover about 20% of the Drosophila genome. Condensate regions have characteristics of asexual evolution that impact gene function: the efficacy of selection and the speed of evolution are lower and the genetic load is higher than in regions of local interference. Our results suggest that multicellular eukaryotes can harbor heterogeneous modes and tempi of evolution within one genome. We argue that this variation generates selection on genome architecture

Eco-evolutionary control of pathogens

Control can alter the eco-evolutionary dynamics of a target pathogen in two ways, by changing its population size and by directed evolution of new functions. Here, we develop a pay-off model of eco-evolutionary control based on strategies of evolution, regulation, and computational forecasting. We apply this model to pathogen control by molecular antibody-antigen binding with a tunable dosage of antibodies. By analytical solu-tion, we obtain optimal dosage protocols and establish a phase diagram with an error threshold delineating parameter regimes of successful and compromised control. The solution identifies few independently measurable fitness parameters that predict the outcome of control. Our analysis shows how optimal con-trol strategies depend on mutation rate and population size of the pathogen, and how monitoring and computational forecast-ing affect protocols and efficiency of control. We argue that these results carry over to more general systems and are elements of an emerging eco-evolutionary control theory.Peer reviewe

Development of a health chair for non-invasive patient monitoring

Tämän diplomityön tarkoituksena oli osallistua Aalto-yliopiston Health Factoryn kehittämän terveystuolin tekniseen kehitykseen. Terveystuolia kehitettiin potilaan terveydentilan seurantaan. Terveystuolin kehitys tapahtui toteuttamalla tarvittavat mittausmoduulit monitorointiasteelle. Diplomityössä esitellään pilottituoleihin valituille moduulille tehdyt LabVIEW-ohjelmat ja tarvittavat kytkennät. Nämä mahdollistivat mittausmoduuleilla monitoroinnin. Tarkoituksena oli myös suunnitella, toteuttaa ja testata pulssiaikaviiveellä toteutettu potilaan systolisen verenpaineen arviointi. Potilaan EKG oli tarkoitus mitata kuivaelektrodeilla, joiden toteutus esitellään. Tarkoituksena oli myös toteuttaa automatisoitu RR- ja QT-intervallien mittaus valitulle EKG-moduulille. Myös tiedon keruu pilottien kehitysvaiheista oli osatavoitteena diplomityössä. Diplomityö esittelee terveystuolin ensimmäisen pilotin, joka toimi koealustana valituille moduuleilla. Sen tarkoituksena oli kokeilla moduulien toimivuus käyttötarkoitukseen. Käyttöönottoon tehdyt tarvittavat LabVIEW-ohjelmat ja kytkennät tehtiin ja ne esitellään. Terveystuolin toinen pilotti toimi koekäyttötuolina ja muistutti enemmän lopullista terveystuolia. Se sisälsi verenpaine-, paino-, plethysmografia-, kudosimpedanssi-, happisaturaatio- ja sykemittaukset. Näihin toteutetut ohjelmat ja kytkennät esitellään. Kolmas pilotti ei valmistunut tämän diplomityön aikana. Sen kehitys oli tarkoituskin jatkua. Tuolin oli tarkoitus sisältää EKG-, paino-, kudosimpedanssi-, happisaturaatio-, syke- ja plethymografiamittaukset sekä systolisen verenpaineen arvioinnin pulssiaikaviiveen avulla. Diplomityö esittelee siihen kuivaelektrodi kytkennän, joka suunniteltiin EKG-mittaukseen. Tehdyt RR-ja QT-intervallien automaattiset mittausmenetelmät esitellään. Suunnitellut menetelmät systolisen verenpaineen arviointiin pulssiaikaviiveellä esitellään. Diplomityössä toteutettiin mittaukset onnistuneesti jokaiseen siinä käytettyyn mittausmoduuliin. Työssä suoritettiin kokeita viidelle henkilölle. Ensinnäkin terveystuolin toisen pilotin mittaukset suoritettiin. Tulokset esitellään ja todettiin että kaikki mittaukset on toteutettavissa. Toiseksi RR- ja QT-intervallien automaattinen laskenta testattiin. LabVIEW-ohjelman laskemia tuloksia verrattiin MatLabilla manuaalisesti mitattuihin tuloksiin. RR-intervalleilla oli pienempi standardi deviaatio ja pienempi mediaani virhe kuin QT-intervalleilla. Ne saavuttivat tyydyttävän tarkkuuden. Viimeiseksi systolisen verenpaineen arviointi pulssiaikaviiveellä kokeiltiin kahdella eri tavalla. Tuloksissa todetaan että pulssiaikaviive ei ole sopiva absoluuttisen verenpaineen arviointiin, eikä sen tarkkuus riitä huomioimaan pieniä verenpaineen muutoksia, mutta se voisi olla sopiva menetelmä pitkä aikaiseen verenpaineen seurantaan.Aalto University’s Health Factory executed development process to realize a health chair for monitoring patient state of health. Aim of this master’s thesis was to participate into the technical development of the health chair. This included designing wanted measurements to pilot designs from selected OEM modules. Including all the necessary coupling and programming to implement modules to monitoring state. The thesis introduces LabVIEW programs and couplings done to these modules on each pilot design. Aim was also to design, execute and test estimating of patient’s systolic blood pressure with pulse transit time method. A design of dry-electrode contact electrocardiography measurement from chosen ECG module was supposed to be realized. Automated calculations of RR and QT intervals were done. The thesis also collects information related to realize pilot design measurements. The thesis introduces health chair’s first pilot design, which worked as test platform to test the chosen measurement modules and verify their compatibility to use. Necessary programs and couplings were made to monitor the measurements. Secondly the master's thesis introduces second health chair pilot design. The design was more developed. It included blood pressure, weight, photoplethysmography, electrical bioimpedance, blood oxygen saturation and heart rate measurements. All these measurement were executed on this health chair. The third pilot design was not finished during this master’s thesis. The third pilot design was designed to include electrocardiography, weight, bioelectrical impedance, blood oxygen saturation, heart rate and photoplethysmography measurement and estimation of systolic blood pressure from pulse transit time. The thesis introduces designed dry-electrode ECG measurement. It introduces two systolic blood pressure estimation methods and RR and QT interval calculations. The calculations and systolic blood pressure estimation methods were made with LabVIEW. The designs of these programs are presented. Every measurement was completed on each module. Tests were made to five persons from different age categories. Firstly, functioning of second pilot design measurements were tested. Aim of the test was to verify that measurements could be executed with second pilot design. Results are presented in the thesis and refer that all the tests were completed. Secondly, usability of RR and QT interval calculations were tested. Aim of the test was to compare the results made with automated LabVIEW measurements and manually calculated result with Matlab. RR interval calculations had smaller standard deviation and median error than QT interval calculations. RR calculations were considered precise. Lastly, systolic blood pressure was estimated with measured pulse transit times from these five test persons. Two different estimation methods were used. Considering the results the method is neither compatible to determine absolute blood pressure or detecting small changes of systolic blood pressure but could be compatible for monitoring systolic blood pressure in long periods

Voiko evoluutiota ennustaa?

Evoluution tutkimus on perinteisesti keskittynyt jo tapahtuneiden asioiden ymmärtämiseen. Genomidatan räjähdyksenomainen kasvu, kokeellinen evoluutio ja evoluutioteorian lisääntynyt ymmärrys ovat avaamassa uuden tutkimussuunnan, jossa nopeasti muuttuvien lajien populaatioiden evoluutiota pyritään ennustamaan. Tässä kirjoituksessa kuvaan, millaiset seikat vaikuttavat evoluution ennustettavuuteen

Class teachers’ experiences and perceptions about character-strengths-based pedagogy : generally and for ADHD students

Tavoitteet. Vahvuuspedagogiikan juuret ovat positiivisen psykologian PERMA-teoriassa. Vahvuuspedagogiikkaa on tutkittu Suomessa 2010-luvulta lähtien enenevässä määrin sekä kansainvälisesti jo 2000-luvun alusta. Tutkimustulokset kertovat sillä olevan myönteisiä vaikutuksia muun muassa inklusiiviseen koulujärjestelmään, kouluiloon, erityisen tuen oppilaiden opiskelumotivaatioon sekä oppilaiden osallisuuteen. Tämän tutkimuksen tavoite oli kartoittaa luokanopettajien kokemuksia ja käsityksiä luonteenvahvuuksien tunnistamisen, tunnustamisen ja kehittämisen merkityksestä ja vaikutuksista. Tutkimuksen kohteena oli myös, mitä merkityksiä luokanopettajat kokevat vahvuuspedagogiikalla olevan neuropsykiatrisesti poikkeaville oppilaille, sekä mitä käsityksiä luokanopettajilla on 5–6-luokkalaisten tietoisuudesta omista luonteenvahvuuksistaan. Tutkimuksen yksi hypoteesi oli, että luokanopettajat kokevat vahvuuspedagogiikan korostuneen merkitykselliseksi ADHD-oppilaiden kanssa. Toinen hypoteesi oli, että vahvuuspedagogiikkaa käytetään Suomen peruskouluissa hyvin vaihtelevalla volyymilla ja erilaisin keinoin. Menetelmät. Tutkimus toteutettiin haastattelu- ja kyselytutkimuksena. Analyysi tehtiin niin laadullisesti kuin määrällisesti sekä mixed methods -menetelmän keinoin. Haastatteluaineisto oli kuusi luokanopettajaa. Kyselyaineisto oli 106 vastaajaa. Tulokset ja johtopäätökset. Tutkimuksen tulokset puoltavat vahvuuspedagogiikan käyttöä peruskoulussa. Koettuun tärkeyteen vaikuttavat paljon toteuttamisen koettu helppous, koulun panostus vahvuuspedagogiikkaan sekä se, miten perusopetuksen opetussuunnitelman perusteet -asiakirjan koetaan ohjaavan vahvuuspedagogiikkaan. Vahvuuspedagogiikan yhtenä yleisimpänä vaikutuksena aineistossa oli sen positiivinen vaikutus esimerkiksi koulumyönteisyyteen ja luokan ilmapiiriin. Haastatteluaineistossa korostui vahvasti vahvuuspedagogiikan ennaltaehkäisevä merkitys, etenkin käyttäytymisen haasteita omaavien oppilaiden tai ADHD-oppilaiden kohdalla.Objectives. Character-strengths-based (CSB) pedagogy stems from positive psychology’s PERMA theory. CSB pedagogy has been studied in Finland to an increasing extent since the 2010s and internationally since the early 2000s. The research results show it has positive effects on, for example, support for the inclusive school system, student well-being, learning motivation among students with special needs, and student participation. The aim of this research was to find out what kind of experiences and perceptions class teachers have about the importance and implications of becoming aware of, acknowledging, and developing character strengths. This research was also interested in what significances CSB pedagogy has among students with neuropsychiatric abnormalities according to class teachers, as well as classroom teachers’ perceptions of 5th–6th graders’ awareness of their own character strengths. One hypothesis was that classroom teachers perceive CSB pedagogy to be particularly important with ADHD students. Another hypothesis was that CSB pedagogy is used in Finnish primary schools with a very varying volume and in different ways. Methods. This research included both interview and questionnaire surveys. The analysis was carried out both qualitatively and quantitatively and by means of mixed methods. Interview material was six classroom teachers. Questionnaire was 106 respondents. Results and conclusions. Results support the use of CSB pedagogy in primary school. Perceived ease of using CSB pedagogy, the school's commitment to CSB pedagogy, and the perceived guidance to CSB pedagogy in national core curriculum for basic education have the biggest effect on the perceived importance of CSB pedagogy. One of the general views of the effects of CSB pedagogy was that it had beneficial effects on school-positivity and classroom atmosphere. The interview material much emphasized the preventive role of CSB pedagogy, especially among students with behavioral challenges or ADHD

Understanding cellular growth strategies via optimal control

Evolutionary prediction and control are increasingly interesting research topics that are expanding to new areas of application. Unravelling and anticipating successful adaptations to different selection pressures becomes crucial when steering rapidly evolving cancer or microbial populations towards a chosen target. Here we introduce and apply a rich theoretical framework of optimal control to understand adaptive use of traits, which in turn allows eco-evolutionarily informed population control. Using adaptive metabolism and microbial experimental evolution as a case study, we show how demographic stochasticity alone can lead to lag time evolution, which appears as an emergent property in our model. We further show that the cycle length used in serial transfer experiments has practical importance as it may cause unintentional selection for specific growth strategies and lag times. Finally, we show how frequency-dependent selection can be incorporated to the state-dependent optimal control framework allowing the modelling of complex eco-evolutionary dynamics. Our study demonstrates the utility of optimal control theory in elucidating organismal adaptations and the intrinsic decision making of cellular communities with high adaptive potential.Peer reviewe

A community effort to create standards for evaluating tumor subclonal reconstruction

Methods for reconstructing tumor evolution are benchmarked in the DREAM Somatic Mutation Calling Tumour Heterogeneity Challenge. Tumor DNA sequencing data can be interpreted by computational methods that analyze genomic heterogeneity to infer evolutionary dynamics. A growing number of studies have used these approaches to link cancer evolution with clinical progression and response to therapy. Although the inference of tumor phylogenies is rapidly becoming standard practice in cancer genome analyses, standards for evaluating them are lacking. To address this need, we systematically assess methods for reconstructing tumor subclonality. First, we elucidate the main algorithmic problems in subclonal reconstruction and develop quantitative metrics for evaluating them. Then we simulate realistic tumor genomes that harbor all known clonal and subclonal mutation types and processes. Finally, we benchmark 580 tumor reconstructions, varying tumor read depth, tumor type and somatic variant detection. Our analysis provides a baseline for the establishment of gold-standard methods to analyze tumor heterogeneity.Peer reviewe

Evaluating genetic drift in time-series evolutionary analysis

The Wright-Fisher model is the most popular population model for describing the behaviour of evolutionary systems with a finite population size. Approximations have commonly been used but the model itself has rarely been tested against time-resolved genomic data. Here, we evaluate the extent to which it can be inferred as the correct model under a likelihood framework. Given genome-wide data from an evolutionary experiment, we validate the Wright-Fisher drift model as the better option for describing evolutionary trajectories in a finite population. This was found by evaluating its performance against a Gaussian model of allele frequency propagation. However, we note a range of circumstances under which standard Wright-Fisher drift cannot be correctly identified. (C) 2017 The Author(s). Published by Elsevier Ltd.Peer reviewe