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Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment
Malaria parasites have small extremely AT-rich genomes: microsatellite repeats (1–9 bp) comprise 11% of the genome and genetic variation in natural populations is dominated by repeat changes in microsatellites rather than point mutations. This experiment was designed to quantify microsatellite mutat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644851/ https://www.ncbi.nlm.nih.gov/pubmed/31273388 http://dx.doi.org/10.1093/gbe/evz140 |
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author | McDew-White, Marina Li, Xue Nkhoma, Standwell C Nair, Shalini Cheeseman, Ian Anderson, Tim J C |
author_facet | McDew-White, Marina Li, Xue Nkhoma, Standwell C Nair, Shalini Cheeseman, Ian Anderson, Tim J C |
author_sort | McDew-White, Marina |
collection | PubMed |
description | Malaria parasites have small extremely AT-rich genomes: microsatellite repeats (1–9 bp) comprise 11% of the genome and genetic variation in natural populations is dominated by repeat changes in microsatellites rather than point mutations. This experiment was designed to quantify microsatellite mutation patterns in Plasmodium falciparum. We established 31 parasite cultures derived from a single parasite cell and maintained these for 114–267 days with frequent reductions to a single cell, so parasites accumulated mutations during ∼13,207 cell divisions. We Illumina sequenced the genomes of both progenitor and end-point mutation accumulation (MA) parasite lines in duplicate to validate stringent calling parameters. Microsatellite calls were 99.89% (GATK), 99.99% (freeBayes), and 99.96% (HipSTR) concordant in duplicate sequence runs from independent sequence libraries, whereas introduction of microsatellite mutations into the reference genome revealed a low false negative calling rate (0.68%). We observed 98 microsatellite mutations. We highlight several conclusions: microsatellite mutation rates (3.12 × 10(−7) to 2.16 × 10(−8)/cell division) are associated with both repeat number and repeat motif like other organisms studied. However, 41% of changes resulted from loss or gain of more than one repeat: this was particularly true for long repeat arrays. Unlike other eukaryotes, we found no insertions or deletions that were not associated with repeats or homology regions. Overall, microsatellite mutation rates are among the lowest recorded and comparable to those in another AT-rich protozoan (Dictyostelium). However, a single infection (>10(11) parasites) will still contain over 2.16 × 10(3) to 3.12 × 10(4) independent mutations at any single microsatellite locus. |
format | Online Article Text |
id | pubmed-6644851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-66448512019-07-25 Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment McDew-White, Marina Li, Xue Nkhoma, Standwell C Nair, Shalini Cheeseman, Ian Anderson, Tim J C Genome Biol Evol Research Article Malaria parasites have small extremely AT-rich genomes: microsatellite repeats (1–9 bp) comprise 11% of the genome and genetic variation in natural populations is dominated by repeat changes in microsatellites rather than point mutations. This experiment was designed to quantify microsatellite mutation patterns in Plasmodium falciparum. We established 31 parasite cultures derived from a single parasite cell and maintained these for 114–267 days with frequent reductions to a single cell, so parasites accumulated mutations during ∼13,207 cell divisions. We Illumina sequenced the genomes of both progenitor and end-point mutation accumulation (MA) parasite lines in duplicate to validate stringent calling parameters. Microsatellite calls were 99.89% (GATK), 99.99% (freeBayes), and 99.96% (HipSTR) concordant in duplicate sequence runs from independent sequence libraries, whereas introduction of microsatellite mutations into the reference genome revealed a low false negative calling rate (0.68%). We observed 98 microsatellite mutations. We highlight several conclusions: microsatellite mutation rates (3.12 × 10(−7) to 2.16 × 10(−8)/cell division) are associated with both repeat number and repeat motif like other organisms studied. However, 41% of changes resulted from loss or gain of more than one repeat: this was particularly true for long repeat arrays. Unlike other eukaryotes, we found no insertions or deletions that were not associated with repeats or homology regions. Overall, microsatellite mutation rates are among the lowest recorded and comparable to those in another AT-rich protozoan (Dictyostelium). However, a single infection (>10(11) parasites) will still contain over 2.16 × 10(3) to 3.12 × 10(4) independent mutations at any single microsatellite locus. Oxford University Press 2019-07-03 /pmc/articles/PMC6644851/ /pubmed/31273388 http://dx.doi.org/10.1093/gbe/evz140 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Research Article McDew-White, Marina Li, Xue Nkhoma, Standwell C Nair, Shalini Cheeseman, Ian Anderson, Tim J C Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment |
title | Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment |
title_full | Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment |
title_fullStr | Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment |
title_full_unstemmed | Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment |
title_short | Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment |
title_sort | mode and tempo of microsatellite length change in a malaria parasite mutation accumulation experiment |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644851/ https://www.ncbi.nlm.nih.gov/pubmed/31273388 http://dx.doi.org/10.1093/gbe/evz140 |
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