The sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem Repeats
Abstract Microsatellites, or Short Tandem Repeats (STRs), are subject to frequent length mutations that involve the loss or gain of an integer number of repeats. This work aimed to investigate the correlation between STRs’ specific repetitive motif composition and mutational dynamics, specifically t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32137-y |
| _version_ | 1797795706698727424 |
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| author | Sofia Antão-Sousa Nádia Pinto Pablo Rende António Amorim Leonor Gusmão |
| author_facet | Sofia Antão-Sousa Nádia Pinto Pablo Rende António Amorim Leonor Gusmão |
| author_sort | Sofia Antão-Sousa |
| collection | DOAJ |
| description | Abstract Microsatellites, or Short Tandem Repeats (STRs), are subject to frequent length mutations that involve the loss or gain of an integer number of repeats. This work aimed to investigate the correlation between STRs’ specific repetitive motif composition and mutational dynamics, specifically the occurrence of single- or multistep mutations. Allelic transmission data, comprising 323,818 allele transfers and 1,297 mutations, were gathered for 35 Y-chromosomal STRs with simple structure. Six structure groups were established: ATT, CTT, TCTA/GATA, GAAA/CTTT, CTTTT, and AGAGAT, according to the repetitive motif present in the DNA leading strand of the markers. Results show that the occurrence of multistep mutations varies significantly among groups of markers defined by the repetitive motif. The group of markers with the highest frequency of multistep mutations was the one with repetitive motif CTTTT (25% of the detected mutations) and the lowest frequency corresponding to the group with repetitive motifs TCTA/GATA (0.93%). Statistically significant differences (α = 0.05) were found between groups with repetitive motifs with different lengths, as is the case of TCTA/GATA and ATT (p = 0.0168), CTT (p < 0.0001) and CTTTT (p < 0.0001), as well as between GAAA/CTTT and CTTTT (p = 0.0102). The same occurred between the two tetrameric groups GAAA/CTTT and TCTA/GATA (p < 0.0001) – the first showing 5.7 times more multistep mutations than the second. When considering the number of repeats of the mutated paternal alleles, statistically significant differences were found for alleles with 10 or 12 repeats, between GATA and ATT structure groups. These results, which demonstrate the heterogeneity of mutational dynamics across repeat motifs, have implications in the fields of population genetics, epidemiology, or phylogeography, and whenever STR mutation models are used in evolutionary studies in general. |
| first_indexed | 2024-03-13T03:22:04Z |
| format | Article |
| id | doaj.art-4edee176bb614ff394f568271714d189 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T03:22:04Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4edee176bb614ff394f568271714d1892023-06-25T11:14:30ZengNature PortfolioScientific Reports2045-23222023-06-011311910.1038/s41598-023-32137-yThe sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem RepeatsSofia Antão-Sousa0Nádia Pinto1Pablo Rende2António Amorim3Leonor Gusmão4Instituto de Investigação e Inovação em Saúde (i3S), University of PortoInstituto de Investigação e Inovação em Saúde (i3S), University of PortoInstituto de Investigação e Inovação em Saúde (i3S), University of PortoInstituto de Investigação e Inovação em Saúde (i3S), University of PortoDNA Diagnostic Laboratory (LDD), State University of Rio de Janeiro (UERJ)Abstract Microsatellites, or Short Tandem Repeats (STRs), are subject to frequent length mutations that involve the loss or gain of an integer number of repeats. This work aimed to investigate the correlation between STRs’ specific repetitive motif composition and mutational dynamics, specifically the occurrence of single- or multistep mutations. Allelic transmission data, comprising 323,818 allele transfers and 1,297 mutations, were gathered for 35 Y-chromosomal STRs with simple structure. Six structure groups were established: ATT, CTT, TCTA/GATA, GAAA/CTTT, CTTTT, and AGAGAT, according to the repetitive motif present in the DNA leading strand of the markers. Results show that the occurrence of multistep mutations varies significantly among groups of markers defined by the repetitive motif. The group of markers with the highest frequency of multistep mutations was the one with repetitive motif CTTTT (25% of the detected mutations) and the lowest frequency corresponding to the group with repetitive motifs TCTA/GATA (0.93%). Statistically significant differences (α = 0.05) were found between groups with repetitive motifs with different lengths, as is the case of TCTA/GATA and ATT (p = 0.0168), CTT (p < 0.0001) and CTTTT (p < 0.0001), as well as between GAAA/CTTT and CTTTT (p = 0.0102). The same occurred between the two tetrameric groups GAAA/CTTT and TCTA/GATA (p < 0.0001) – the first showing 5.7 times more multistep mutations than the second. When considering the number of repeats of the mutated paternal alleles, statistically significant differences were found for alleles with 10 or 12 repeats, between GATA and ATT structure groups. These results, which demonstrate the heterogeneity of mutational dynamics across repeat motifs, have implications in the fields of population genetics, epidemiology, or phylogeography, and whenever STR mutation models are used in evolutionary studies in general.https://doi.org/10.1038/s41598-023-32137-y |
| spellingShingle | Sofia Antão-Sousa Nádia Pinto Pablo Rende António Amorim Leonor Gusmão The sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem Repeats Scientific Reports |
| title | The sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem Repeats |
| title_full | The sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem Repeats |
| title_fullStr | The sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem Repeats |
| title_full_unstemmed | The sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem Repeats |
| title_short | The sequence of the repetitive motif influences the frequency of multistep mutations in Short Tandem Repeats |
| title_sort | sequence of the repetitive motif influences the frequency of multistep mutations in short tandem repeats |
| url | https://doi.org/10.1038/s41598-023-32137-y |
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