---
_id: '10767'
abstract:
- lang: eng
text: The t-haplotype of mice is a classical model for autosomal transmission distortion.
A largely non-recombining variant of the proximal region of chromosome 17, it
is transmitted to more than 90% of the progeny of heterozygous males through the
disabling of sperm carrying a standard chromosome. While extensive genetic and
functional work has shed light on individual genes involved in drive, much less
is known about the evolution and function of the rest of its hundreds of genes.
Here, we characterize the sequence and expression of dozens of t-specific transcripts
and of their chromosome 17 homologues. Many genes showed reduced expression of
the t-allele, but an equal number of genes showed increased expression of their
t-copy, consistent with increased activity or a newly evolved function. Genes
on the t-haplotype had a significantly higher non-synonymous substitution rate
than their homologues on the standard chromosome, with several genes harbouring
dN/dS ratios above 1. Finally, the t-haplotype has acquired at least two genes
from other chromosomes, which show high and tissue-specific expression. These
results provide a first overview of the gene content of this selfish element,
and support a more dynamic evolutionary scenario than expected of a large genomic
region with almost no recombination.
acknowledgement: "This project has received funding from the European Research Council
under the European Union’s Horizon 2020 research and innovation program (grant agreement
no. 715257) and from the Swiss National Science Foundation (grant no. 310030_189145).\r\nWe
thank Jari Garbely of the Department of Evolutionary Biology and Environmental Studies,
University of Zurich, Zurich, Switzerland, for conducting the PCR verification.
Barbara\r\nKonig, Gabi Stichel and A.K.L. collected mouse tissue samples, from the
field study led by R.K.K. "
article_processing_charge: No
article_type: original
author:
- first_name: Réka K
full_name: Kelemen, Réka K
id: 48D3F8DE-F248-11E8-B48F-1D18A9856A87
last_name: Kelemen
- first_name: Marwan N
full_name: Elkrewi, Marwan N
id: 0B46FACA-A8E1-11E9-9BD3-79D1E5697425
last_name: Elkrewi
orcid: 0000-0002-5328-7231
- first_name: Anna K.
full_name: Lindholm, Anna K.
last_name: Lindholm
- first_name: Beatriz
full_name: Vicoso, Beatriz
id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
last_name: Vicoso
orcid: 0000-0002-4579-8306
citation:
ama: 'Kelemen RK, Elkrewi MN, Lindholm AK, Vicoso B. Novel patterns of expression
and recruitment of new genes on the t-haplotype, a mouse selfish chromosome. Proceedings
of the Royal Society B: Biological Sciences. 2022;289(1968):20211985. doi:10.1098/rspb.2021.1985'
apa: 'Kelemen, R. K., Elkrewi, M. N., Lindholm, A. K., & Vicoso, B. (2022).
Novel patterns of expression and recruitment of new genes on the t-haplotype,
a mouse selfish chromosome. Proceedings of the Royal Society B: Biological
Sciences. The Royal Society. https://doi.org/10.1098/rspb.2021.1985'
chicago: 'Kelemen, Réka K, Marwan N Elkrewi, Anna K. Lindholm, and Beatriz Vicoso.
“Novel Patterns of Expression and Recruitment of New Genes on the T-Haplotype,
a Mouse Selfish Chromosome.” Proceedings of the Royal Society B: Biological
Sciences. The Royal Society, 2022. https://doi.org/10.1098/rspb.2021.1985.'
ieee: 'R. K. Kelemen, M. N. Elkrewi, A. K. Lindholm, and B. Vicoso, “Novel patterns
of expression and recruitment of new genes on the t-haplotype, a mouse selfish
chromosome,” Proceedings of the Royal Society B: Biological Sciences, vol.
289, no. 1968. The Royal Society, p. 20211985, 2022.'
ista: 'Kelemen RK, Elkrewi MN, Lindholm AK, Vicoso B. 2022. Novel patterns of expression
and recruitment of new genes on the t-haplotype, a mouse selfish chromosome. Proceedings
of the Royal Society B: Biological Sciences. 289(1968), 20211985.'
mla: 'Kelemen, Réka K., et al. “Novel Patterns of Expression and Recruitment of
New Genes on the T-Haplotype, a Mouse Selfish Chromosome.” Proceedings of the
Royal Society B: Biological Sciences, vol. 289, no. 1968, The Royal Society,
2022, p. 20211985, doi:10.1098/rspb.2021.1985.'
short: 'R.K. Kelemen, M.N. Elkrewi, A.K. Lindholm, B. Vicoso, Proceedings of the
Royal Society B: Biological Sciences 289 (2022) 20211985.'
date_created: 2022-02-20T23:01:31Z
date_published: 2022-02-09T00:00:00Z
date_updated: 2023-08-02T14:26:07Z
day: '09'
ddc:
- '570'
department:
- _id: BeVi
doi: 10.1098/rspb.2021.1985
ec_funded: 1
external_id:
isi:
- '000752812800012'
pmid:
- '35135349'
file:
- access_level: open_access
checksum: 27042a3706ae52a919fed1ac114bf7bb
content_type: application/pdf
creator: dernst
date_created: 2022-02-21T08:17:38Z
date_updated: 2022-02-21T08:17:38Z
file_id: '10779'
file_name: 2022_ProceedingsRoyalSocB_Kelemen.pdf
file_size: 2366976
relation: main_file
success: 1
file_date_updated: 2022-02-21T08:17:38Z
has_accepted_license: '1'
intvolume: ' 289'
isi: 1
issue: '1968'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '02'
oa: 1
oa_version: Published Version
page: '20211985'
pmid: 1
project:
- _id: 250BDE62-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715257'
name: Prevalence and Influence of Sexual Antagonism on Genome Evolution
publication: 'Proceedings of the Royal Society B: Biological Sciences'
publication_identifier:
eissn:
- '14712954'
publication_status: published
publisher: The Royal Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Novel patterns of expression and recruitment of new genes on the t-haplotype,
a mouse selfish chromosome
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 289
year: '2022'
...
---
_id: '6983'
abstract:
- lang: eng
text: Malaria, a disease caused by parasites of the Plasmodium genus, begins when
Plasmodium-infected mosquitoes inject malaria sporozoites while searching for
blood. Sporozoites migrate from the skin via blood to the liver, infect hepatocytes,
and form liver stages which in mice 48 h later escape into blood and cause clinical
malaria. Vaccine-induced activated or memory CD8 T cells are capable of locating
and eliminating all liver stages in 48 h, thus preventing the blood-stage disease.
However, the rules of how CD8 T cells are able to locate all liver stages within
a relatively short time period remains poorly understood. We recently reported
formation of clusters consisting of variable numbers of activated CD8 T cells
around Plasmodium yoelii (Py)-infected hepatocytes. Using a combination of experimental
data and mathematical models we now provide additional insights into mechanisms
of formation of these clusters. First, we show that a model in which cluster formation
is driven exclusively by T-cell-extrinsic factors, such as variability in “attractiveness”
of different liver stages, cannot explain distribution of cluster sizes in different
experimental conditions. In contrast, the model in which cluster formation is
driven by the positive feedback loop (i.e., larger clusters attract more CD8 T
cells) can accurately explain the available data. Second, while both Py-specific
CD8 T cells and T cells of irrelevant specificity (non-specific CD8 T cells) are
attracted to the clusters, we found no evidence that non-specific CD8 T cells
play a role in cluster formation. Third and finally, mathematical modeling suggested
that formation of clusters occurs rapidly, within few hours after adoptive transfer
of CD8 T cells, thus illustrating high efficiency of CD8 T cells in locating their
targets in complex peripheral organs, such as the liver. Taken together, our analysis
provides novel insights into and attempts to discriminate between alternative
mechanisms driving the formation of clusters of antigen-specific CD8 T cells in
the liver.
article_number: '2153'
article_processing_charge: No
article_type: original
author:
- first_name: Réka K
full_name: Kelemen, Réka K
id: 48D3F8DE-F248-11E8-B48F-1D18A9856A87
last_name: Kelemen
orcid: 0000-0002-8489-9281
- first_name: H
full_name: Rajakaruna, H
last_name: Rajakaruna
- first_name: IA
full_name: Cockburn, IA
last_name: Cockburn
- first_name: VV
full_name: Ganusov, VV
last_name: Ganusov
citation:
ama: Kelemen RK, Rajakaruna H, Cockburn I, Ganusov V. Clustering of activated CD8
T cells around Malaria-infected hepatocytes is rapid and is driven by antigen-specific
cells. Frontiers in Immunology. 2019;10. doi:10.3389/fimmu.2019.02153
apa: Kelemen, R. K., Rajakaruna, H., Cockburn, I., & Ganusov, V. (2019). Clustering
of activated CD8 T cells around Malaria-infected hepatocytes is rapid and is driven
by antigen-specific cells. Frontiers in Immunology. Frontiers. https://doi.org/10.3389/fimmu.2019.02153
chicago: Kelemen, Réka K, H Rajakaruna, IA Cockburn, and VV Ganusov. “Clustering
of Activated CD8 T Cells around Malaria-Infected Hepatocytes Is Rapid and Is Driven
by Antigen-Specific Cells.” Frontiers in Immunology. Frontiers, 2019. https://doi.org/10.3389/fimmu.2019.02153.
ieee: R. K. Kelemen, H. Rajakaruna, I. Cockburn, and V. Ganusov, “Clustering of
activated CD8 T cells around Malaria-infected hepatocytes is rapid and is driven
by antigen-specific cells,” Frontiers in Immunology, vol. 10. Frontiers,
2019.
ista: Kelemen RK, Rajakaruna H, Cockburn I, Ganusov V. 2019. Clustering of activated
CD8 T cells around Malaria-infected hepatocytes is rapid and is driven by antigen-specific
cells. Frontiers in Immunology. 10, 2153.
mla: Kelemen, Réka K., et al. “Clustering of Activated CD8 T Cells around Malaria-Infected
Hepatocytes Is Rapid and Is Driven by Antigen-Specific Cells.” Frontiers in
Immunology, vol. 10, 2153, Frontiers, 2019, doi:10.3389/fimmu.2019.02153.
short: R.K. Kelemen, H. Rajakaruna, I. Cockburn, V. Ganusov, Frontiers in Immunology
10 (2019).
date_created: 2019-11-04T15:50:06Z
date_published: 2019-09-20T00:00:00Z
date_updated: 2023-08-30T07:18:23Z
day: '20'
ddc:
- '570'
department:
- _id: BeVi
doi: 10.3389/fimmu.2019.02153
external_id:
isi:
- '000487187000001'
pmid:
- '31616407'
file:
- access_level: open_access
checksum: 68d1708f7aa412544159b498ef17a6b9
content_type: application/pdf
creator: dernst
date_created: 2019-11-04T15:54:00Z
date_updated: 2020-07-14T12:47:46Z
file_id: '6984'
file_name: 2019_FrontiersImmonology_Kelemen.pdf
file_size: 2083061
relation: main_file
file_date_updated: 2020-07-14T12:47:46Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Immunology
publication_identifier:
issn:
- 1664-3224
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Clustering of activated CD8 T cells around Malaria-infected hepatocytes is
rapid and is driven by antigen-specific cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2019'
...
---
_id: '542'
abstract:
- lang: eng
text: The t-haplotype, a mouse meiotic driver found on chromosome 17, has been a
model for autosomal segregation distortion for close to a century, but several
questions remain regarding its biology and evolutionary history. A recently published
set of population genomics resources for wild mice includes several individuals
heterozygous for the t-haplotype, which we use to characterize this selfish element
at the genomic and transcriptomic level. Our results show that large sections
of the t-haplotype have been replaced by standard homologous sequences, possibly
due to occasional events of recombination, and that this complicates the inference
of its history. As expected for a long genomic segment of very low recombination,
the t-haplotype carries an excess of fixed nonsynonymous mutations compared to
the standard chromosome. This excess is stronger for regions that have not undergone
recent recombination, suggesting that occasional gene flow between the t and the
standard chromosome may provide a mechanism to regenerate coding sequences that
have accumulated deleterious mutations. Finally, we find that t-complex genes
with altered expression largely overlap with deleted or amplified regions, and
that carrying a t-haplotype alters the testis expression of genes outside of the
t-complex, providing new leads into the pathways involved in the biology of this
segregation distorter.
article_processing_charge: No
article_type: original
author:
- first_name: Réka K
full_name: Kelemen, Réka K
id: 48D3F8DE-F248-11E8-B48F-1D18A9856A87
last_name: Kelemen
orcid: 0000-0002-8489-9281
- first_name: Beatriz
full_name: Vicoso, Beatriz
id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
last_name: Vicoso
orcid: 0000-0002-4579-8306
citation:
ama: Kelemen RK, Vicoso B. Complex history and differentiation patterns of the t-haplotype,
a mouse meiotic driver. Genetics. 2018;208(1):365-375. doi:10.1534/genetics.117.300513
apa: Kelemen, R. K., & Vicoso, B. (2018). Complex history and differentiation
patterns of the t-haplotype, a mouse meiotic driver. Genetics. Genetics
Society of America. https://doi.org/10.1534/genetics.117.300513
chicago: Kelemen, Réka K, and Beatriz Vicoso. “Complex History and Differentiation
Patterns of the T-Haplotype, a Mouse Meiotic Driver.” Genetics. Genetics
Society of America, 2018. https://doi.org/10.1534/genetics.117.300513.
ieee: R. K. Kelemen and B. Vicoso, “Complex history and differentiation patterns
of the t-haplotype, a mouse meiotic driver,” Genetics, vol. 208, no. 1.
Genetics Society of America, pp. 365–375, 2018.
ista: Kelemen RK, Vicoso B. 2018. Complex history and differentiation patterns of
the t-haplotype, a mouse meiotic driver. Genetics. 208(1), 365–375.
mla: Kelemen, Réka K., and Beatriz Vicoso. “Complex History and Differentiation
Patterns of the T-Haplotype, a Mouse Meiotic Driver.” Genetics, vol. 208,
no. 1, Genetics Society of America, 2018, pp. 365–75, doi:10.1534/genetics.117.300513.
short: R.K. Kelemen, B. Vicoso, Genetics 208 (2018) 365–375.
date_created: 2018-12-11T11:47:04Z
date_published: 2018-01-01T00:00:00Z
date_updated: 2024-02-21T13:48:27Z
day: '01'
ddc:
- '576'
department:
- _id: BeVi
doi: 10.1534/genetics.117.300513
ec_funded: 1
external_id:
isi:
- '000419356300024'
file:
- access_level: open_access
checksum: 2123845e7031a0cf043905be160f9e69
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:15:14Z
date_updated: 2020-07-14T12:46:50Z
file_id: '5132'
file_name: IST-2018-1058-v1+1_365.full__1_.pdf
file_size: 1311661
relation: main_file
file_date_updated: 2020-07-14T12:46:50Z
has_accepted_license: '1'
intvolume: ' 208'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 365 - 375
project:
- _id: 250BDE62-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715257'
name: Prevalence and Influence of Sexual Antagonism on Genome Evolution
publication: Genetics
publication_status: published
publisher: Genetics Society of America
publist_id: '7274'
pubrep_id: '1058'
quality_controlled: '1'
related_material:
record:
- id: '5571'
relation: popular_science
status: public
- id: '5572'
relation: popular_science
status: public
scopus_import: '1'
status: public
title: Complex history and differentiation patterns of the t-haplotype, a mouse meiotic
driver
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 208
year: '2018'
...