---
OA_place: publisher
_id: '17206'
abstract:
- lang: eng
  text: "Males and females exhibit numerous differences, from the initial stages of
    sex determination to the\r\ndevelopment of secondary sexual characteristics. In
    Drosophila, these differences have been\r\nthoroughly studied. Extensive research
    has been performed to understand the role and molecular\r\nmode of action of central
    sex in determining switch genes, such as transformer (tra) and Sex-lethal\r\n(Sxl).
    Furthermore, studies have highlighted differential gene expression as an essential
    mechanism to\r\ncreate sexual dimorphism. An alternative path to sexual dimorphism
    that has been less explored is\r\nalternative splicing, the mechanism through
    which genes can produce multiple transcripts with\r\ndistinct properties and functions.
    The primary switch sex-determining gene Sxl is a good example of\r\nthe role of
    alternative splicing for sex-specific functions: the inclusion of a specific exon
    determines\r\nthe male or female form of the protein, which in turn switches on
    either the male or female\r\ndevelopmental pathway. The genes that act upstream
    of Sxl and determine which form is expressed -\r\nthe counter genes - have received
    less attention. This thesis addresses two critical questions about\r\nthe molecular
    encoding of sexes in the Drosophila melanogaster genome: First, the use of splice
    forms\r\nin male and female tissues in D. melanogaster is examined, inferring
    the molecular and evolutionary\r\nparameters shaping the diversity of the splicing
    landscape. Second, the behaviour of counter genes in\r\nDrosophila-related species
    is investigated, shedding light on potential changes leading to their\r\nincorporation
    into the sex-determination pathway.\r\nFor the alternative splicing analyses,
    long-read RNA sequencing of testes, ovaries, female and male\r\nmidguts, heads,
    and whole bodies was performed. A novel pipeline was developed to assign unique\r\ntranscript
    identifiers for each sequence of exons and introns in the read, enabling detailed\r\ncomparisons
    of splicing variants in each tissue/sex. Alternative splicing was found to be
    more\r\npervasive in females than males (22,201 exclusive splice forms in females
    versus 12,631 in males),\r\nespecially when comparing ovaries to other tissues.
    The ovaries alone displayed 15,299 exclusive\r\nsplice forms, suggesting most
    female exclusive splice forms originate there. Genome location and gene\r\nage
    were also correlated with the number of splice forms per gene. In particular,
    the X and 4th\r\nchromosomes (Muller elements A and F) showed more splice forms
    per gene than other\r\nchromosomes. Additionally, genes older than 63 million
    years exhibited more splice forms per gene\r\nthan younger genes. Our results
    suggest that alternative splicing is more prevalent than previously\r\nbelieved,
    with numerous female-exclusive forms, age, and location playing significant roles
    in shaping\r\nits prevalence.\r\nFor the counter genes analyses, we combined published
    gene expression, genomic, and gene\r\ninteraction data from various clades (Bactrocera
    jarvisi, B. oleae, Ceratitis capitata, Mus musculus,\r\nCaenorhabditis elegans,
    Homo sapiens, and D. melanogaster). The counter genes scute (sc), extra\r\nmacrochaetae
    (emc), groucho (gro), deadpan (dpn), daughterless (da), runt (run), Sxl, hermaphrodite\r\n(her),
    and tra maintain conserved Muller element locations between C. capitata and D.
    melanogaster,\r\nwhich are most of the counter genes identified in the C. capitata
    genome. Their expression patterns\r\nduring early embryogenesis in B. jarvisi
    and D. melanogaster are also similar for counter genes dpn,\r\ngro, da, and emc.
    However, Sxl and sc are also found to have more extreme expression ratios between\r\nthe
    species. Lastly, gene interactions within the counter genes are conserved, with
    da-sc and gro-dpn\r\ninteractions occurring in Drosophila, worms, humans, and
    mice. Interactions such as dpn-sc, dpn-da,\r\nda-emc, and gro-run are present
    in Drosophila, mice, and humans, suggesting these genes were\r\nrecruited by ancestral
    characteristics, primarily during embryogenesis. The conserved expression,\r\nlocation,
    and interactions of counter genes suggest serendipitous recruitment of such genes
    instead\r\nof a change in those characteristics as they were recruited for this
    function. "
acknowledged_ssus:
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Julia
  full_name: Raices, Julia
  id: 3EE67F22-F248-11E8-B48F-1D18A9856A87
  last_name: Raices
citation:
  ama: 'Raices J. Novel approaches to studying alternative splicing in Drosophila
    Melanogaster : Insights into sex-specific gene expression and the evolution of
    sex determination. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17206">10.15479/at:ista:17206</a>'
  apa: 'Raices, J. (2024). <i>Novel approaches to studying alternative splicing in
    Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution
    of sex determination</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:17206">https://doi.org/10.15479/at:ista:17206</a>'
  chicago: 'Raices, Julia. “Novel Approaches to Studying Alternative Splicing in Drosophila
    Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of
    Sex Determination.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:17206">https://doi.org/10.15479/at:ista:17206</a>.'
  ieee: 'J. Raices, “Novel approaches to studying alternative splicing in Drosophila
    Melanogaster : Insights into sex-specific gene expression and the evolution of
    sex determination,” Institute of Science and Technology Austria, 2024.'
  ista: 'Raices J. 2024. Novel approaches to studying alternative splicing in Drosophila
    Melanogaster : Insights into sex-specific gene expression and the evolution of
    sex determination. Institute of Science and Technology Austria.'
  mla: 'Raices, Julia. <i>Novel Approaches to Studying Alternative Splicing in Drosophila
    Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of
    Sex Determination</i>. Institute of Science and Technology Austria, 2024, doi:<a
    href="https://doi.org/10.15479/at:ista:17206">10.15479/at:ista:17206</a>.'
  short: 'J. Raices, Novel Approaches to Studying Alternative Splicing in Drosophila
    Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of
    Sex Determination, Institute of Science and Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-07-05T14:15:29Z
date_published: 2024-07-05T00:00:00Z
date_updated: 2026-04-07T13:03:22Z
day: '05'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: BeVi
- _id: GradSch
doi: 10.15479/at:ista:17206
ec_funded: 1
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has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-sa/4.0/
month: '07'
oa: 1
oa_version: Published Version
page: '82'
project:
- _id: 250BDE62-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715257'
  name: Prevalence and Influence of Sexual Antagonism on Genome Evolution
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Beatriz
  full_name: Vicoso, Beatriz
  id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
  last_name: Vicoso
  orcid: 0000-0002-4579-8306
title: 'Novel approaches to studying alternative splicing in Drosophila Melanogaster
  : Insights into sex-specific gene expression and the evolution of sex determination'
tmp:
  image: /images/cc_by_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode
  name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC
    BY-SA 4.0)
  short: CC BY-SA (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...