EVOLUTIONARY ANALYSES PROVIDE INSIGHT INTO HOST-PATHOGEN INTERACTIONS AND DIET-RELATED ADAPTATIONS
Tesi di Dottorato
Data di Pubblicazione:
2017
Citazione:
EVOLUTIONARY ANALYSES PROVIDE INSIGHT INTO HOST-PATHOGEN INTERACTIONS AND DIET-RELATED ADAPTATIONS / C. Pontremoli ; tutor: M. Biasin ; co-tutor: M. Sironi ; direttore del dottorato: M. Clerici. DIPARTIMENTO DI SCIENZE BIOMEDICHE E CLINICHE "L. SACCO", 2017 Feb 10. 29. ciclo, Anno Accademico 2016. [10.13130/pontremoli-chiara_phd2017-02-10].
Abstract:
ABSTRACT
INTRODUCTION
Genetic diversity plays an important role in the survival and adaptability of all species. When a population environment (meaning, for instance, climatic conditions, pathogens, and food availability) changes, the population is subject to a selective pressure. Variation in the population gene pool provides variable traits which can be selected for, via natural selection, leading to an adaptive change to survive. Genetic diversity is generated by a combination of different evolutionary processes such as mutation, genetic drift, migration and natural selection.
Natural selection leaves a distinctive molecular signature in genomes. Such molecular signatures can be detected with evolutionary tests that can be divided into those that search for selection at the inter-species level (e.g., human versus primates and mammals) and those that focus on within-species data (e.g., among human populations). In my work, I used evolutionary studies to analyze genes under different selective pressures.
In a first study, I investigate the evolutionary history of genes possibly involved in diet adaptation. Changes in food availability and diet likely created strong selective pressures on multiple biological processes. In humans, the agricultural revolution favored carbohydrate consumption. I exploit the availability of genome sequences from different organisms, together with resequencing data of ancient DNA samples to perform a comprehensive evolutionary analysis of genes involved in sugar absorption/digestion at the brush-border and to test when adaptive alleles arose.
In a second set of studies, I use evolutionary analyses to investigate the interaction between host proteins and viral/protozoan/bacterial protein products. Molecules that participate in immune response are expected to be engaged in a constant arms-race with pathogens and to harbour the molecular signatures of such a conflict. I thus investigate the evolutionary history of genes involved in immune defense, such as antiviral sensing proteins, genes with IFN-inducible properties and antiviral effectors. I also investigate the evolutionary history of the complement system, an innate immunity effector, and of bacterial-encoded complement- interacting proteins.
Nevertheless, not only genes with specific defense function, but also molecules involved in central homeostatic processes may be engaged in genetic conflicts with pathogens. This is exemplified by (i) the sterol transporter NPC1, used as receptor for filoviruses entry and (ii) basigin, a multifunctional protein with a role in trophoblast function and in spermatogenesis which is used for erythrocyte invasion by Plasmodium falciparum. I therefore study the evolutionary history of these genes and of their viral/microbial interactors.
AIM OF THE WORK
The purpose of my project is to use evolutionary analyses to investigate and describe adaptive events at candidate genes subject to different selective pressures, in species ranging from mammals to viruses/protozoa/bacteria. In particular, I focus on inter-species and population genetics-phylogenetics analyses, with the aim to detect positive selection acting over long evolutionary timescales.
MATERIALS AND METHODS
Mammalian and pathogen coding gene sequences were retrieved from public databases (Ensembl, UCSC and NCBI) or obtained by direct sequencing. Information from the Neandertal and Denisova high-coverage genomes, as well as from a hunter-gatherer Mesolithic European from Spain and a Paleolithic Siberian was derived from previous works.
Sequences were aligned using RevTrans 2.0 utility, PRANK, and unreliably aligned codons were then filtered using GUIDANCE. Since recombination can be mistaken as positive selection, all alignments were screened for t
Tipologia IRIS:
Tesi di dottorato
Elenco autori:
C. Pontremoli
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