Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR
Simple sequence repeats (SSRs) are very common short repeats in eukaryotic genomes. “Long” SSRs are considered “hypermutable” sequences because they exhibit a high rate of expansion and contraction. Because they are potentially deleterious, long SSRs tend to be uncommon in coding sequences. However, several genes contain long SSRs in their exonic sequences. Here, we identify 1,291 human genes that host a mononucleotide SSR long enough to be prone to expansion or contraction, being called hypermutable hereafter. On the basis of Gene Ontology annotations, we show that only a restricted number of functions are overrepresented among those hypermutable genes including cell cycle and maintenance of DNA integrity. Using a probabilistic model, we show that genes involved in these functions are expected to host long SSRs because they tend to be long and/or are biased in nucleotide composition. Finally, we show that for almost all functions we observe fewer hypermutable sequences than expected under a neutral model. There are however interesting exceptions, for example, genes involved in protein and RNA transport, as well as meiosis and mismatch repair functions that have as many hypermutable genes as expected under neutrality. Conversely, there are functions (e.g., collagen-related genes) where hypermutable genes are more often avoided than in other functions. Our results show that, even though several functions harbor unusually long SSR in their exons, long SSRs are deleterious sequences in almost all functions and are removed by purifying selection. The strength of this purifying selection however greatly varies from function to function. We discuss possible explanations for this intriguing result.
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Subjects: | 000 - Autres thèmes, L10 - Génétique et amélioration des animaux, U10 - Informatique, mathématiques et statistiques, genre humain, mutation, génétique animale, séquence nucléotidique, méthode statistique, http://aims.fao.org/aos/agrovoc/c_4586, http://aims.fao.org/aos/agrovoc/c_5014, http://aims.fao.org/aos/agrovoc/c_49986, http://aims.fao.org/aos/agrovoc/c_27583, http://aims.fao.org/aos/agrovoc/c_7377, |
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dig-cirad-fr-5773282024-01-28T22:51:52Z http://agritrop.cirad.fr/577328/ http://agritrop.cirad.fr/577328/ Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR. Loire Etienne, Praz Françoise, Higuet Dominique, Netter Pierre, Achaz Guillaume. 2009. Molecular Biology and Evolution, 26 (1) : 111-121.https://doi.org/10.1093/molbev/msn230 <https://doi.org/10.1093/molbev/msn230> Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR Loire, Etienne Praz, Françoise Higuet, Dominique Netter, Pierre Achaz, Guillaume eng 2009 Molecular Biology and Evolution 000 - Autres thèmes L10 - Génétique et amélioration des animaux U10 - Informatique, mathématiques et statistiques genre humain mutation génétique animale séquence nucléotidique méthode statistique http://aims.fao.org/aos/agrovoc/c_4586 http://aims.fao.org/aos/agrovoc/c_5014 http://aims.fao.org/aos/agrovoc/c_49986 http://aims.fao.org/aos/agrovoc/c_27583 http://aims.fao.org/aos/agrovoc/c_7377 Simple sequence repeats (SSRs) are very common short repeats in eukaryotic genomes. “Long” SSRs are considered “hypermutable” sequences because they exhibit a high rate of expansion and contraction. Because they are potentially deleterious, long SSRs tend to be uncommon in coding sequences. However, several genes contain long SSRs in their exonic sequences. Here, we identify 1,291 human genes that host a mononucleotide SSR long enough to be prone to expansion or contraction, being called hypermutable hereafter. On the basis of Gene Ontology annotations, we show that only a restricted number of functions are overrepresented among those hypermutable genes including cell cycle and maintenance of DNA integrity. Using a probabilistic model, we show that genes involved in these functions are expected to host long SSRs because they tend to be long and/or are biased in nucleotide composition. Finally, we show that for almost all functions we observe fewer hypermutable sequences than expected under a neutral model. There are however interesting exceptions, for example, genes involved in protein and RNA transport, as well as meiosis and mismatch repair functions that have as many hypermutable genes as expected under neutrality. Conversely, there are functions (e.g., collagen-related genes) where hypermutable genes are more often avoided than in other functions. Our results show that, even though several functions harbor unusually long SSR in their exons, long SSRs are deleterious sequences in almost all functions and are removed by purifying selection. The strength of this purifying selection however greatly varies from function to function. We discuss possible explanations for this intriguing result. article info:eu-repo/semantics/article Journal Article info:eu-repo/semantics/publishedVersion http://agritrop.cirad.fr/577328/1/MBE.pdf text cc_by info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/4.0/ https://doi.org/10.1093/molbev/msn230 10.1093/molbev/msn230 info:eu-repo/semantics/altIdentifier/doi/10.1093/molbev/msn230 info:eu-repo/semantics/altIdentifier/purl/https://doi.org/10.1093/molbev/msn230 |
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000 - Autres thèmes L10 - Génétique et amélioration des animaux U10 - Informatique, mathématiques et statistiques genre humain mutation génétique animale séquence nucléotidique méthode statistique http://aims.fao.org/aos/agrovoc/c_4586 http://aims.fao.org/aos/agrovoc/c_5014 http://aims.fao.org/aos/agrovoc/c_49986 http://aims.fao.org/aos/agrovoc/c_27583 http://aims.fao.org/aos/agrovoc/c_7377 000 - Autres thèmes L10 - Génétique et amélioration des animaux U10 - Informatique, mathématiques et statistiques genre humain mutation génétique animale séquence nucléotidique méthode statistique http://aims.fao.org/aos/agrovoc/c_4586 http://aims.fao.org/aos/agrovoc/c_5014 http://aims.fao.org/aos/agrovoc/c_49986 http://aims.fao.org/aos/agrovoc/c_27583 http://aims.fao.org/aos/agrovoc/c_7377 |
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000 - Autres thèmes L10 - Génétique et amélioration des animaux U10 - Informatique, mathématiques et statistiques genre humain mutation génétique animale séquence nucléotidique méthode statistique http://aims.fao.org/aos/agrovoc/c_4586 http://aims.fao.org/aos/agrovoc/c_5014 http://aims.fao.org/aos/agrovoc/c_49986 http://aims.fao.org/aos/agrovoc/c_27583 http://aims.fao.org/aos/agrovoc/c_7377 000 - Autres thèmes L10 - Génétique et amélioration des animaux U10 - Informatique, mathématiques et statistiques genre humain mutation génétique animale séquence nucléotidique méthode statistique http://aims.fao.org/aos/agrovoc/c_4586 http://aims.fao.org/aos/agrovoc/c_5014 http://aims.fao.org/aos/agrovoc/c_49986 http://aims.fao.org/aos/agrovoc/c_27583 http://aims.fao.org/aos/agrovoc/c_7377 Loire, Etienne Praz, Françoise Higuet, Dominique Netter, Pierre Achaz, Guillaume Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR |
description |
Simple sequence repeats (SSRs) are very common short repeats in eukaryotic genomes. “Long” SSRs are considered “hypermutable” sequences because they exhibit a high rate of expansion and contraction. Because they are potentially deleterious, long SSRs tend to be uncommon in coding sequences. However, several genes contain long SSRs in their exonic sequences. Here, we identify 1,291 human genes that host a mononucleotide SSR long enough to be prone to expansion or contraction, being called hypermutable hereafter. On the basis of Gene Ontology annotations, we show that only a restricted number of functions are overrepresented among those hypermutable genes including cell cycle and maintenance of DNA integrity. Using a probabilistic model, we show that genes involved in these functions are expected to host long SSRs because they tend to be long and/or are biased in nucleotide composition. Finally, we show that for almost all functions we observe fewer hypermutable sequences than expected under a neutral model. There are however interesting exceptions, for example, genes involved in protein and RNA transport, as well as meiosis and mismatch repair functions that have as many hypermutable genes as expected under neutrality. Conversely, there are functions (e.g., collagen-related genes) where hypermutable genes are more often avoided than in other functions. Our results show that, even though several functions harbor unusually long SSR in their exons, long SSRs are deleterious sequences in almost all functions and are removed by purifying selection. The strength of this purifying selection however greatly varies from function to function. We discuss possible explanations for this intriguing result. |
format |
article |
topic_facet |
000 - Autres thèmes L10 - Génétique et amélioration des animaux U10 - Informatique, mathématiques et statistiques genre humain mutation génétique animale séquence nucléotidique méthode statistique http://aims.fao.org/aos/agrovoc/c_4586 http://aims.fao.org/aos/agrovoc/c_5014 http://aims.fao.org/aos/agrovoc/c_49986 http://aims.fao.org/aos/agrovoc/c_27583 http://aims.fao.org/aos/agrovoc/c_7377 |
author |
Loire, Etienne Praz, Françoise Higuet, Dominique Netter, Pierre Achaz, Guillaume |
author_facet |
Loire, Etienne Praz, Françoise Higuet, Dominique Netter, Pierre Achaz, Guillaume |
author_sort |
Loire, Etienne |
title |
Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR |
title_short |
Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR |
title_full |
Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR |
title_fullStr |
Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR |
title_full_unstemmed |
Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR |
title_sort |
hypermutability of genes in homo sapiens due to the hosting of long mono-ssr |
url |
http://agritrop.cirad.fr/577328/ http://agritrop.cirad.fr/577328/1/MBE.pdf |
work_keys_str_mv |
AT loireetienne hypermutabilityofgenesinhomosapiensduetothehostingoflongmonossr AT prazfrancoise hypermutabilityofgenesinhomosapiensduetothehostingoflongmonossr AT higuetdominique hypermutabilityofgenesinhomosapiensduetothehostingoflongmonossr AT netterpierre hypermutabilityofgenesinhomosapiensduetothehostingoflongmonossr AT achazguillaume hypermutabilityofgenesinhomosapiensduetothehostingoflongmonossr |
_version_ |
1792498877401661440 |