---
OA_place: publisher
_id: '1121'
abstract:
- lang: eng
  text: "Horizontal gene transfer (HGT), the lateral acquisition of genes across existing
    species\r\nboundaries, is a major evolutionary force shaping microbial genomes
    that facilitates\r\nadaptation to new environments as well as resistance to antimicrobial
    drugs. As such,\r\nunderstanding the mechanisms and constraints that determine
    the outcomes of HGT\r\nevents is crucial to understand the dynamics of HGT and
    to design better strategies to\r\novercome the challenges that originate from
    it.\r\nFollowing the insertion and expression of a newly transferred gene, the
    success of an\r\nHGT event will depend on the fitness effect it has on the recipient
    (host) cell. Therefore,\r\npredicting the impact of HGT on the genetic composition
    of a population critically\r\ndepends on the distribution of fitness effects (DFE)
    of horizontally transferred genes.\r\nHowever, to date, we have little knowledge
    of the DFE of newly transferred genes, and\r\nhence little is known about the
    shape and scale of this distribution.\r\nIt is particularly important to better
    understand the selective barriers that determine\r\nthe fitness effects of newly
    transferred genes. In spite of substantial bioinformatics\r\nefforts to identify
    horizontally transferred genes and selective barriers, a systematic\r\nexperimental
    approach to elucidate the roles of different selective barriers in defining\r\nthe
    fate of a transfer event has largely been absent. Similarly, although the fact
    that\r\nenvironment might alter the fitness effect of a horizontally transferred
    gene may seem\r\nobvious, little attention has been given to it in a systematic
    experimental manner.\r\nIn this study, we developed a systematic experimental
    approach that consists of\r\ntransferring 44 arbitrarily selected Salmonella typhimurium
    orthologous genes into an\r\nEscherichia coli host, and estimating the fitness
    effects of these transferred genes at a\r\nconstant expression level by performing
    competition assays against the wild type.\r\nIn chapter 2, we performed one-to-one
    competition assays between a mutant strain\r\ncarrying a transferred gene and
    the wild type strain. By using flow cytometry we\r\nestimated selection coefficients
    for the transferred genes with a precision level of 10-3,and obtained the DFE
    of horizontally transferred genes. We then investigated if these\r\nfitness effects
    could be predicted by any of the intrinsic properties of the genes, namely,\r\nfunctional
    category, degree of complexity (protein-protein interactions), GC content,\r\ncodon
    usage and length. Our analyses revealed that the functional category and length\r\nof
    the genes act as potential selective barriers. Finally, using the same procedure
    with\r\nthe endogenous E. coli orthologs of these 44 genes, we demonstrated that
    gene dosage is\r\nthe most prominent selective barrier to HGT.\r\nIn chapter 3,
    using the same set of genes we investigated the role of environment on the\r\nsuccess
    of HGT events. Under six different environments with different levels of stress\r\nwe
    performed more complex competition assays, where we mixed all 44 mutant strains\r\ncarrying
    transferred genes with the wild type strain. To estimate the fitness effects of\r\ngenes
    relative to wild type we used next generation sequencing. We found that the DFEs\r\nof
    horizontally transferred genes are highly dependent on the environment, with\r\nabundant
    gene–by-environment interactions. Furthermore, we demonstrated a\r\nrelationship
    between average fitness effect of a gene across all environments and its\r\nenvironmental
    variance, and thus its predictability. Finally, in spite of the fitness effects\r\nof
    genes being highly environment-dependent, we still observed a common shape of\r\nDFEs
    across all tested environments."
acknowledgement: "This study was supported by European Research Council ERC CoG 2014
  – EVOLHGT,\r\nunder the grant number 648440.\r\n\r\nIt is a pleasure to thank the
  many people who made this thesis possible.\r\nI would like to first thank my advisor,
  Jonathan Paul Bollback for providing guidance in\r\nall aspects of my life, encouragement,
  sound advice, and good teaching over the last six\r\nyears.\r\nI would also like
  to thank the members of my dissertation committee – Călin C. Guet\r\nand John F.
  Baines – not only for their time and guidance, but for their intellectual\r\ncontributions
  to my development as a scientist.\r\nI would like to thank Flavia Gama and Rodrigo
  Redondo who have taught me all the\r\nskills in the laboratory with their graciousness
  and friendship. Also special thanks to\r\nBollback group for their support and for
  providing a stimulating and fun environment:\r\nIsabella Tomanek, Fabienne Jesse,
  Claudia Igler, and Pavel Payne.\r\nJerneja Beslagic is not only an amazing assistant,
  she also has a smile brighter and\r\nwarmer than the sunshine, bringing happiness
  to every moment. Always keep your light\r\nNeja, I will miss our invaluable chatters
  a lot."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Hande
  full_name: Acar, Hande
  id: 2DDF136A-F248-11E8-B48F-1D18A9856A87
  last_name: Acar
  orcid: 0000-0003-1986-9753
citation:
  ama: Acar H. Selective barriers to horizontal gene transfer. 2016.
  apa: Acar, H. (2016). <i>Selective barriers to horizontal gene transfer</i>. Institute
    of Science and Technology Austria.
  chicago: Acar, Hande. “Selective Barriers to Horizontal Gene Transfer.” Institute
    of Science and Technology Austria, 2016.
  ieee: H. Acar, “Selective barriers to horizontal gene transfer,” Institute of Science
    and Technology Austria, 2016.
  ista: Acar H. 2016. Selective barriers to horizontal gene transfer. Institute of
    Science and Technology Austria.
  mla: Acar, Hande. <i>Selective Barriers to Horizontal Gene Transfer</i>. Institute
    of Science and Technology Austria, 2016.
  short: H. Acar, Selective Barriers to Horizontal Gene Transfer, Institute of Science
    and Technology Austria, 2016.
corr_author: '1'
date_created: 2018-12-11T11:50:16Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2026-07-29T11:17:47Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: JoBo
- _id: GradSch
doi_confirm: '1'
ec_funded: 1
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  checksum: 94bbbc754c36115bf37f8fc11fad43c4
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has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: '75'
project:
- _id: 2578D616-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '648440'
  name: Selective Barriers to Horizontal Gene Transfer
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6239'
status: public
supervisor:
- first_name: Jonathan P
  full_name: Bollback, Jonathan P
  id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
  last_name: Bollback
  orcid: 0000-0002-4624-4612
title: Selective barriers to horizontal gene transfer
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2016'
...