Intra-specific variation in avian malaria : Linking infection dynamics to haplotypes
(2023)- Abstract
- Avian Malaria infects thousands of species of birds across the Aves class. The most widespread (geographically and phylogenetically)
morphological species is Plasmodium relictum, and of that, the mitochondrial lineage of SGS1 is the most common and invasive. It infects
146 bird species, with large differences in infection outcome, from low intensity chronic disease to shorter, highly virulent infections. In
Paper 1, I studied the gene expression of SGS1 in experimentally infected birds pre and post maximum parasitemia. The parasitemia
varied widely between birds and especially over the course of the infection. These differences were significantly linked to genes related
to cell replication and cellular movement in high... (More) - Avian Malaria infects thousands of species of birds across the Aves class. The most widespread (geographically and phylogenetically)
morphological species is Plasmodium relictum, and of that, the mitochondrial lineage of SGS1 is the most common and invasive. It infects
146 bird species, with large differences in infection outcome, from low intensity chronic disease to shorter, highly virulent infections. In
Paper 1, I studied the gene expression of SGS1 in experimentally infected birds pre and post maximum parasitemia. The parasitemia
varied widely between birds and especially over the course of the infection. These differences were significantly linked to genes related
to cell replication and cellular movement in high parasitemia infections and cellular metabolism in low parasitemia infections. We found
that over time, variation in gene expression increased between samples, possibly illustrating individual responses of the parasites to their
hosts, and a desynchronisation in their lifecycles. Paper 2 explored the phylogeography of SGS1, and its related lineage GRW11, in the
palearctic region. Because the lineage system is defined by a highly conserved single mitochondrial gene, the nuclear polymorphic cell
invasion gene, merozoite surface protein 1 (msp1), was selected to study the genetic variation present in infected resident and migrant host
populations. We found extremely little variation, suggesting SGS1and GRW11 in Europe have an epidemic population structure, or there
is strong purifying selection pressure on the msp1 gene despite the wide host range. Paper 3 developed a genomic sequence capture method
using 1035 probes designed for SGS1, and tested it on a range of SGS1, GRW11, and GRW4 samples. The probes effectively isolated
DNA from all three lineages, but sequencing success was low for samples with less than 1% parasitemia. We selected 25 genes to describe
the higher-than-expected variation within SGS1 and with GRW11 and GRW4 samples. In Paper 4, two different host sources of SGS1
infected blood were used to infect two groups of canaries. The groups differed in parasitemia and mortality, and from each group the three
birds with largest differences in infection outcome were selected for RNA sequencing to survey the underlying genomic variation. The
source of the infection reliably separated the samples phylogenetically, with relatively less variation observed within the groups. This
suggests that an infection is made up of a population of genetically diverse parasites. Paper 5 expanded on this idea by using the genomic
sequence capture method from Paper 3 and refined bioinformatic methods from Paper 4 on some of the same samples from Paper 1.
Samples collected at the same time points (8 and 20 days post infection) were sequenced. This allowed analyses of how the predominant
haplotypes change during an infection, and then link those haplotypes to the disease severity. We found that the least suppressed/most
virulent haplotypes had genetic variants in genes related to cell invasion and immune evasion. The combined results of my thesis have
far-reaching implications that extend beyond the particular organism under investigation. The notion of genetic diversity within a single
infections and the resulting parasite population dynamics offers exciting prospects for future research. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4ee1d063-aad3-47b1-956e-cf963b5e2af1
- author
- Kalbskopf, Victor LU
- supervisor
-
- Olof Hellgren LU
- Dag Ahrén LU
- opponent
-
- Professor Sehgal, Ravinder, Dept of Biology, San Francisco State University, USA
- organization
- publishing date
- 2023-08-04
- type
- Thesis
- publication status
- published
- subject
- keywords
- avian malaria, phyogenetics, population genetics, evolution
- pages
- 191 pages
- publisher
- Lund
- defense location
- Blå hallen, Ekologihuset, Lund
- defense date
- 2023-09-22 09:00:00
- ISBN
- 978-91-8039-771-1
- 978-91-8039-772-8
- language
- English
- LU publication?
- yes
- id
- 4ee1d063-aad3-47b1-956e-cf963b5e2af1
- date added to LUP
- 2023-08-28 11:44:13
- date last changed
- 2023-08-28 14:17:06
@phdthesis{4ee1d063-aad3-47b1-956e-cf963b5e2af1,
abstract = {{Avian Malaria infects thousands of species of birds across the Aves class. The most widespread (geographically and phylogenetically)<br/>morphological species is Plasmodium relictum, and of that, the mitochondrial lineage of SGS1 is the most common and invasive. It infects<br/>146 bird species, with large differences in infection outcome, from low intensity chronic disease to shorter, highly virulent infections. In<br/>Paper 1, I studied the gene expression of SGS1 in experimentally infected birds pre and post maximum parasitemia. The parasitemia<br/>varied widely between birds and especially over the course of the infection. These differences were significantly linked to genes related<br/>to cell replication and cellular movement in high parasitemia infections and cellular metabolism in low parasitemia infections. We found<br/>that over time, variation in gene expression increased between samples, possibly illustrating individual responses of the parasites to their<br/>hosts, and a desynchronisation in their lifecycles. Paper 2 explored the phylogeography of SGS1, and its related lineage GRW11, in the<br/>palearctic region. Because the lineage system is defined by a highly conserved single mitochondrial gene, the nuclear polymorphic cell<br/>invasion gene, merozoite surface protein 1 (msp1), was selected to study the genetic variation present in infected resident and migrant host<br/>populations. We found extremely little variation, suggesting SGS1and GRW11 in Europe have an epidemic population structure, or there<br/>is strong purifying selection pressure on the msp1 gene despite the wide host range. Paper 3 developed a genomic sequence capture method<br/>using 1035 probes designed for SGS1, and tested it on a range of SGS1, GRW11, and GRW4 samples. The probes effectively isolated<br/>DNA from all three lineages, but sequencing success was low for samples with less than 1% parasitemia. We selected 25 genes to describe<br/>the higher-than-expected variation within SGS1 and with GRW11 and GRW4 samples. In Paper 4, two different host sources of SGS1<br/>infected blood were used to infect two groups of canaries. The groups differed in parasitemia and mortality, and from each group the three<br/>birds with largest differences in infection outcome were selected for RNA sequencing to survey the underlying genomic variation. The<br/>source of the infection reliably separated the samples phylogenetically, with relatively less variation observed within the groups. This<br/>suggests that an infection is made up of a population of genetically diverse parasites. Paper 5 expanded on this idea by using the genomic<br/>sequence capture method from Paper 3 and refined bioinformatic methods from Paper 4 on some of the same samples from Paper 1.<br/>Samples collected at the same time points (8 and 20 days post infection) were sequenced. This allowed analyses of how the predominant<br/>haplotypes change during an infection, and then link those haplotypes to the disease severity. We found that the least suppressed/most<br/>virulent haplotypes had genetic variants in genes related to cell invasion and immune evasion. The combined results of my thesis have<br/>far-reaching implications that extend beyond the particular organism under investigation. The notion of genetic diversity within a single<br/>infections and the resulting parasite population dynamics offers exciting prospects for future research.}},
author = {{Kalbskopf, Victor}},
isbn = {{978-91-8039-771-1}},
keywords = {{avian malaria; phyogenetics; population genetics; evolution}},
language = {{eng}},
month = {{08}},
publisher = {{Lund}},
school = {{Lund University}},
title = {{Intra-specific variation in avian malaria : Linking infection dynamics to haplotypes}},
url = {{https://lup.lub.lu.se/search/files/156065540/Victor_Kalbskopf_WEBB.pdf}},
year = {{2023}},
}