Phylodynamic Patterns in Pathogen Ecology and Evolution.

The rapid evolution of viral pathogens requires us to consider epidemiological, ecological and evolutionary processes as coupled together and occurring at the same timescale. Rotavirus and influenza account for high levels of morbidity and mortality worldwide and are two important examples of such dynamics. In this work, I investigate the different evolutionary and ecological processes that shape the antigenic structure and phylogenetic characteristics of these two viruses. In the first part of my work, I use a theoretical model of influenza A/H3N2 to identify the relative importance of antigenic novelty, competition between lineages, and changes in the susceptibility of the host population to circulating strains in determining the evolutionary and epidemiological trajectory of the virus. I develop this model further to correspond with patterns of immunity and infection observed in rotavirus, and investigate how reassortment, the swapping of gene segments between viruses, influences the formation and replacement of rotavirus genotypes through immune mediated processes. In the second part of my work, I use a tool (SeasMig), which I developed, to infer alternative stochastically generated migration and mutation events along phylogenetic trees in a Bayesian manner. Using SeasMig, I first show how the seasonality of A/H3N2 influenza incidence corresponds to rates of immigration and emigration of the virus. Subsequently, I tease out the different evolutionary and ecological processes, which drive changes in the US rotavirus population following onset of routine vaccination. My work has implications for identifying likely evolutionary mechanisms, which may lead to reduced vaccine efficacy, and for vaccine strain selection.PhDBioinformaticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113494/1/dzinder_1.pd

Urban park characteristics, genetic variation, and historical demography of white-footed mouse (Peromyscus leucopus) populations in New York City

Severe fragmentation is a typical fate of native remnant habitats in cities, and urban wildlife with limited dispersal ability are predicted to lose genetic variation in isolated urban patches. However, little information exists on the characteristics of urban green spaces required to conserve genetic variation. In this study, we examine whether isolation in New York City (NYC) parks results in genetic bottlenecks in white-footed mice (Peromyscus leucopus), and test the hypotheses that park size and time since isolation are associated with genetic variability using nonlinear regression and information-theoretic model selection. White-footed mice have previously been documented to exhibit male-biased dispersal, which may create disparities in genetic variation between males and females in urban parks. We use genotypes of 18 neutral microsatellite data and four different statistical tests to assess this prediction. Given that sex-biased dispersal may create disparities between population genetic patterns inferred from bi- vs. uni-parentally inherited markers, we also sequenced a 324 bp segment of the mitochondrial D-loop for independent inferences of historical demography in urban P. leucopus. We report that isolation in urban parks does not necessarily result in genetic bottlenecks; only three out of 14 populations in NYC parks exhibited a signature of a recent bottleneck at 18 neutral microsatellite loci. Mouse populations in larger urban parks, or parks that have been isolated for shorter periods of time, also do not generally contain greater genetic variation than populations in smaller parks. These results suggest that even small networks of green spaces may be sufficient to maintain the evolutionary potential of native species with certain characteristics. We also found that isolation in urban parks results in weak to nonexistent sex-biased dispersal in a species known to exhibit male-biased dispersal in less fragmented environments. In contrast to nuclear loci, mitochondrial D-loop haplotypes exhibited a mutational pattern of demographic expansion after a recent bottleneck or selective sweep. Estimates of the timing of this expansion suggest that it occurred concurrent with urbanization of NYC over the last few dozens to hundreds of years. Given the general non-neutrality of mtDNA in many systems and evidence of selection on related coding sequences in urban P. leucopus, we argue that the P. leucopus mitochondrial genome experienced recent negative selection against haplotypes not favored in isolated urban parks. In general, rapid adaptive evolution driven by urbanization, global climate change, and other human-caused factors is underappreciated by evolutionary biologists, but many more cases will likely be documented in the near future

Characterization of the genetic structure of the azorean population

Tese de doutoramento em Bioquímica (Genética Molecular), apresentada à Universidade de Lisboa através da Faculdade de Ciências, 200

Effective Population Size, Demography, and Viability of Eastern Massasaugas (Sistrurus catenatus) in Southwest Michigan

As humans increasingly exploit natural areas, wildlife populations face a growing number of threats that often result in population decline and isolation. Small, isolated populations are vulnerable to extirpation due to both genetic and demographic factors. Yet, low detectability of many imperiled species often precludes the collection of population-level data important for assessing population viability and implementing successful conservation. The eastern massasauga (Sistrurus catenatus) is a cryptic pitviper that has been extirpated throughout much of its historic range due to agricultural conversion of wetland habitat and other synergistic threats. Consequently, this species is federally listed as threatened in both the United States and Canada, and most remnant populations are believed to be small and isolated. However, most extant populations lack data on population size and long-term survival rates, making effective management, monitoring, and viability assessments difficult. To address these data deficiencies, I estimated the genetic effective population size (Ne) and census population size (Nc) for eastern massasaugas at two sites in southwest Michigan. My results revealed small Nc, with approximately 108 (95% CI = 87–165) and 148 (95% CI = 102–295) adults estimated at the study sites in Cass County and Barry County, respectively. Estimates of Ne were even smaller: approximately 29.5 (95% CI = 22.2–40.5) for Cass County and 44.2 (95% CI =29.7–73.4) for Barry County. Additionally, Ne/Nc ratios were similar across study sites. Secondly, for the Barry County population, I used mark-recapture data spanning 2008–2016 to estimate annual apparent survival rates of adults. Using these estimates and other parameter values obtained from my site and a nearby population, I modeled population viability over the next 100 years. I also performed a sensitivity analysis to assess the relative influence of model parameters on extinction risk. I estimated annual apparent survival rates of 0.79 (95% CI = 0.68–0.87) for adult males and 0.78 (95% CI = 0.68–0.86) for adult females. Results of my sensitivity analysis suggest that actions promoting high survival of adult females should be a management priority, followed by activities that facilitate high reproductive output and neonate survival

Distribution, abundance, social and genetic structures of Indo-Pacific bottlenose dolphins (Tursiops aduncus) in Perth metropolitan waters, Western Australia

In heterogeneous coastal and estuarine environments, dolphins are exposed to varying levels of human activities. Consequently, it is important to identify and characterise fine-scale population structuring based on ecological, social, spatial and genetic data to develop appropriate conservation and management strategies. This thesis focused on identifying subpopulations of Indo-Pacific bottlenose dolphins (Tursiops aduncus) inhabiting Perth waters, Western Australia (WA). Using spatial and social data collected over four years of boat-based photo-identification surveys, I: i) estimated abundances, survival and movement rates using a Multistate Closed Robust Design approach; and ii) examined the social structure and home range using social association and network analyses. I used microsatellite loci and mtDNA markers to investigate the genetic population structure of dolphins at metropolitan (Perth) and regional (c. 1000 km of coastline) scales. High capture probabilities, high survival and constant abundances described a subpopulation with high fidelity in an estuary. In contrast, low captures, emigration and fluctuating abundances suggested transient use and low fidelity in an open coastline region. Overall, dolphins formed four socially and geographically distinct, mixed-sex subpopulations that varied in association strength, site fidelity and residency patterns. Curiously, home range overlap and genetic relatedness did not affect the association patterns. In Perth metropolitan waters, a source-sink relationship was suggested between a subpopulation inhabiting a semi-enclosed embayment and three other subpopulations, including the estuarine subpopulation. On a broader scale, the Perth metapopulation was genetically distinct from other populations along the WA southwestern coastline, with little to no migration from and into other populations. The subpopulations present in Perth waters should each be regarded as a distinct management unit, with a particular focus on protecting the estuarine subpopulation, which is small, has limited connection with adjacent subpopulations and is more vulnerable because of the intensity and diversity of anthropogenic threats present in the estuary

Postglacial colonization and parallel evolution of metal tolerance in the polyploid Cerastium alpinum

The Fennoscandian flora is characterized by a high frequency of polyploids, probably because they were more successful than diploid plants in colonizing after the last Ice Age. The first postglacial colonizers were likely poor competitors and became displaced from the lowlands as forests advanced. Consequently, many of these pioneers are currently found only above tree line. However, some have persisted within the forests on open habitats such as naturally toxic serpentine soils where succession is arrested at the pioneer stage. These populations represent relicts of former widely distributed plants. The polyploid Cerastium alpinum L. (Caryophyllaceae) grows on serpentine soils throughout Fennoscandia. C. alpinum populations on different soil types provide a model system for the study of the early postglacial colonization history of Fennoscandia. Genetic markers showed that C. alpinum populations in western Fennoscandia differ genetically from eastern populations, suggesting a two-way colonization. The two lineages meet in a hybrid zone in Northern Scandinavia where a high degree of genetic variation was found. Plants from Fennoscandia and the Western Arctic (Canada, Greenland and Iceland) shared many AFLP fragments, which suggests they originate from common refugia. The Fennoscandian populations were more distantly related to the populations in potential refugia in southern Europe. In fact, the northern populations contained AFLP fragments not found in populations in the Pyrenees and the Alps. Lack of chloroplast DNA variation indicates fast postglacial range expansions and/or a recent origin of C. alpinum. Crosses were made to establish the inheritance of enzyme markers. The results strengthen the evidence for an allopolyploid origin of C. alpinum. Adjacent serpentine and non-serpentine populations of C. alpinum provide a model system of natural replicates to test whether adaptation to serpentine is constitutive (common for all populations) or locally evolved. A growth experiment with high concentrations of nickel and magnesium, two metals that limit the fertility of serpentine soils, showed that the degree of metal tolerance reflects site-specific soil conditions. Since local adaptation was found in both the eastern and the western immigration lineages, the postglacial colonization of Fennoscandia has involved parallel evolution of metal tolerance in C. alpinum

Seasonality in the migration and establishment of H3N2 Influenza lineages with epidemic growth and decline

Background: Influenza A/H3N2 has been circulating in humans since 1968, causing considerable morbidity and mortality. Although H3N2 incidence is highly seasonal, how such seasonality contributes to global phylogeographic migration dynamics has not yet been established. Results: Incorporating seasonally varying migration rates improves the modeling of migration. In our global model, windows of increased immigration map to the seasonal timing of epidemic spread, while windows of increased emigration map to epidemic decline. Seasonal patterns also correlate with the probability that local lineages go extinct and fail to contribute to long term viral evolution, as measured through the trunk of the phylogeny. However, the fraction of the trunk in each community was found to be better determined by its overall human population size Conclusions: Seasonal migration and rapid turnover within regions is sustained by the invasion of 'fertile epidemic grounds' at the end of older epidemics. Thus, the current emphasis on connectivity, including air-travel, should be complemented with a better understanding of the conditions and timing required for successful establishment.Models which account for migration seasonality will improve our understanding of the seasonal drivers of influenza,enhance epidemiological predictions, and ameliorate vaccine updating by identifying strains that not only escape immunity but also have the seasonal opportunity to establish and spread. Further work is also needed on additional conditions that contribute to the persistence and long term evolution of influenza within the human population,such as spatial heterogeneity with respect to climate and seasonalityComment: in BMC Evolutionary Biology 2014, 1

Macro- and Microevolution of Languages: Exploring Linguistic Divergence with Approaches from Evolutionary Biology

There are more than 7000 languages in the world, and many of these have emerged through linguistic divergence. While questions related to the drivers of linguistic diversity have been studied before, including studies with quantitative methods, there is no consensus as to which factors drive linguistic divergence, and how. In the thesis, I have studied linguistic divergence with a multidisciplinary approach, applying the framework and quantitative methods of evolutionary biology to language data. With quantitative methods, large datasets may be analyzed objectively, while approaches from evolutionary biology make it possible to revisit old questions (related to, for example, the shape of the phylogeny) with new methods, and adopt novel perspectives to pose novel questions. My chief focus was on the effects exerted on the speakers of a language by environmental and cultural factors. My approach was thus an ecological one, in the sense that I was interested in how the local environment affects humans and whether this human-environment connection plays a possible role in the divergence process. I studied this question in relation to the Uralic language family and to the dialects of Finnish, thus covering two different levels of divergence. However, as the Uralic languages have not previously been studied using quantitative phylogenetic methods, nor have population genetic methods been previously applied to any dialect data, I first evaluated the applicability of these biological methods to language data. I found the biological methodology to be applicable to language data, as my results were rather similar to traditional views as to both the shape of the Uralic phylogeny and the division of Finnish dialects. I also found environmental conditions, or changes in them, to be plausible inducers of linguistic divergence: whether in the first steps in the divergence process, i.e. dialect divergence, or on a large scale with the entire language family. My findings concerning Finnish dialects led me to conclude that the functional connection between linguistic divergence and environmental conditions may arise through human cultural adaptation to varying environmental conditions. This is also one possible explanation on the scale of the Uralic language family as a whole. The results of the thesis bring insights on several different issues in both a local and a global context. First, they shed light on the emergence of the Finnish dialects. If the approach used in the thesis is applied to the dialects of other languages, broader generalizations may be drawn as to the inducers of linguistic divergence. This again brings us closer to understanding the global patterns of linguistic diversity. Secondly, the quantitative phylogeny of the Uralic languages, with estimated times of language divergences, yields another hypothesis as to the shape and age of the language family tree. In addition, the Uralic languages can now be added to the growing list of language families studied with quantitative methods. This will allow broader inferences as to global patterns of language evolution, and more language families can be included in constructing the tree of the world’s languages. Studying history through language, however, is only one way to illuminate the human past. Therefore, thirdly, the findings of the thesis, when combined with studies of other language families, and those for example in genetics and archaeology, bring us again closer to an understanding of human history.Monet maailman yli 7000 kielestä ovat syntyneet erkaantumisprosessin kautta. Tällöin yhdestä kielestä muotoutuu eri tekijöiden vaikutuksesta aikojen saatossa useampia kieliä. Kielten erkaantumiseen vaikuttavia tekijöitä on tutkittu aiemminkin ja myös laskennallisia menetelmiä käyttäen. Vielä on kuitenkin epäselvää mitkä kaikki tekijät voivat vaikuttaa kielten erkaantumiseen ja miten. Tutkin väitöskirjassani kielten erkaantumiseen vaikuttavia tekijöitä. Lähestymistapani on monitieteinen, sillä sovellan laskennallisia evoluutiobiologian menetelmiä ja teorioita kieliaineistoon. Laskennalliset menetelmät mahdollistavat suurien aineistojen objektiivisen analysoinnin, kun taas evoluutiobiologisen lähestymistavan avulla voin muodostaa uudenlaisia tutkimuskysymyksiä ja käyttää uusia menetelmiä vastatakseni aiemmin esitettyihin kysymyksiin (esimerkiksi sukupuun muotoon liittyen). Tutkimuksessani keskityin selvittämään kielten erkaantumista ihmisen ekologian kannalta. Toisin sanoen olin kiinnostunut ympäristö- ja/tai kulttuuritekijöiden vaikutuksesta kielenpuhujiin ja siitä, voiko tämä kytkös olla osallisena kielten erkaantumisprosessissa. Tutkin kysymystä tämän prosessin kahdessa eri vaiheessa: sen alussa ennen kuin eriytyminen on kokonaan tapahtunut, ja sen jo tapahduttua. Murteiden eriytyminen vastaa prossessin alkuvaihetta, ja tutkin sitä suomen kielen murreaineistoa käyttäen. Tapahtuneita erkaantumisia tutkin sukupuista, joita tein uralilaisten kielten sanastoaineistosta. Koska uralilaisia kieliä ei ole aiemmin tutkittu vastaavanlaisin laskennallisin menetelmin eikä käyttämiäni populaatiogenetiikan menetelmiä ole käytetty aiemmin mihinkään murreaineistoon, testasin aluksi näiden menetelmien soveltuvuutta aineistojeni analysointiin. Totesin biologisten menetelmien soveltuvan kieliaineiston analysointiin, sillä tulokseni vastasivat perinteisiä näkemyksiä sekä uralilaisen sukupuun muodosta että suomen murrejaosta. Lisäksi havaitsin, että erot ympäristöoloissa mahdollisesti vaikuttavat kielten erkaantumiseen. Tämä oli havaittavissa niin eriytymisprosessin varhaisissa vaiheissa murteiden välillä kuin myös koko kieliryhmän eriytymisiä tutkittaessa. Koska ihmisten tiedetään usein sopeutuvan vallitseviin ympäristöolosuhteisiin kulttuurisopeumien avulla, päättelin murretutkimusteni tuloksista, että juuri kieltenpuhujien kulttuurinen sopeutuminen paikallisiin ympäristöolosuhteisiin saattaisi toimia puhujapopulaatioita erottavana tekijänä ja täten kytköksenä ympäristöerojen ja kielellisen erkaantumisen välillä. Tämä voisi mahdollisesti selittää myös uralilaisten kielten erkaantumisia. Väitöstutkimukseni tulokset tuovat uusia näkemyksiä kielten erkaantumiseen niin paikallisella kuin maailmanlaajuisellakin tasolla. Havaintoni ympäristöerojen mahdollisesta vaikutuksesta suomen murteiden muotoutumisessa herättää kysymyksen löytöni yleistettävyydestä myös muihin kieliin ja niiden murteisiin. Koska murteiden erkaantuminen on ensimmäinen vaihe kielen eriytymisprosessissa, on murteiden muotoutumista tutkimalla mahdollista myös selvittää, mitkä tekijät ovat aikaansaaneet maailmanlaajuisen kielten kirjon. Tästä syystä tarvitaan vastaavanlaisia tutkimuksia myös muiden kielten murteista. Esitän väitöskirjassani myös uralilaisten kielten laskennallisesti tehdyn sukupuun, jota voidaan verrata vastaavilla menetelmillä tehtyihin muiden kieliryhmien puihin. Tämän vertailun kautta on mahdollista selvittää onko kielisukupuiden muodossa jotain maailmanlaajuisia säännönmukaisuuksia, josta voi edelleen tehdä päätelmiä kieliin vaikuttavista lainalaisuuksista. Ihmiskunnan historian ja esihistorian selvittäminen on haasteellinen palapeli, jossa eri tieteenalojen palasia yhteen sovittelemalla voidaan päästä lähemmäksi yleistä ymmärrystä menneisyydestä. Väitöstutkimukseni on pieni osa tätä kokonaisuutta, mutta yhdistelemällä havaintojani niin muista kieliryhmistä tehtyihin havaintoihin kuin myös esimerkiksi arkeologian ja genetiikan tuloksiin, olemme taas askeleen lähempänä tätä tavoitetta.Siirretty Doriast

Speciation and genetic diversity in Centaurea subsect. Phalolepis in Anatolia

14 p., mapas, tablasMountains of Anatolia are one of the main Mediterranean biodiversity hotspots and their richness in endemic species amounts for 30% of the flora. Two main factors may account for this high diversity: the complex orography and its role as refugia during past glaciations. We have investigated seven narrow endemics of Centaurea subsection Phalolepis from Anatolia by means of microsatellites and ecological niche modelling (ENM), in order to analyse genetic polymorphisms and getting insights into their speciation. Despite being narrow endemics, all the studied species show moderate to high SSR genetic diversity. Populations are genetically isolated, but exchange of genes probably occurred at glacial maxima (likely through the Anatolian mountain arches as suggested by the ENM). The lack of correlation between genetic clusters and (morpho) species is interpreted as a result of allopatric diversification on the basis of a shared gene pool. As suggested in a former study in Greece, post-glacial isolation in mountains would be the main driver of diversification in these plants; mountains of Anatolia would have acted as plant refugia, allowing the maintenance of high genetic diversity. Ancient gene flow between taxa that became sympatric during glaciations may also have contributed to the high levels of genetic diversity.This work was supported by the Spanish Ministerio de Ciencia e Innovación [project CGL2010/18631] and Generalitat de Catalunya [Ajuts a Grups de Recerca Consolidats 2014-SGR514-GREB]Peer reviewe