dorsal/arxiv
View SchemaSemiconservative replication in the quasispecies model II: Generalization to arbitrary lesion repair probabilities
| Authors | Emmanuel Tannenbaum, James L. Sherley, Eugene I. Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0407004 |
| URL | https://arxiv.org/abs/q-bio/0407004 |
Abstract
This paper extends the semiconservative quasispecies equations to account for arbitrary post-replication lesion repair efficiency. Such an extension could be an important tool for understanding processes such as cancer development and stem cell growth. Starting from the quasispecies dynamics over the space of genomes, we derive an equivalent dynamics over the space of ordered sequence pairs. From this set of equations, we are able to derive the infinite sequence length form of the dynamics for a class of ``master-genome''-based fitness landscapes. We use these equations to solve for a ``generalized'' single-fitness-peak landscape, where the master genome can sustain a maximum number of lesions and remain viable. The central pattern that emerges from our studies is that imperfect lesion repair often leads to increased mutational robustness over semiconservative replication with completely efficient lesion repair. The reason for this is that imperfect lesion repair breaks some of the correlation between the parent and daughter strands, thereby preventing replication errors from destroying the information in the original genome. The result is a delayed error catastrophe over that expected from the original semiconservative quasispecies model. In particular, we show that when only of the strands is necessary for conferring viability, then, when lesion repair is turned off, a semiconservatively replicating system becomes an effectively conservatively replicating one.
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"abstract": "This paper extends the semiconservative quasispecies equations to account for\narbitrary post-replication lesion repair efficiency. Such an extension could be\nan important tool for understanding processes such as cancer development and\nstem cell growth. Starting from the quasispecies dynamics over the space of\ngenomes, we derive an equivalent dynamics over the space of ordered sequence\npairs. From this set of equations, we are able to derive the infinite sequence\nlength form of the dynamics for a class of ``master-genome\u0027\u0027-based fitness\nlandscapes. We use these equations to solve for a ``generalized\u0027\u0027\nsingle-fitness-peak landscape, where the master genome can sustain a maximum\nnumber of lesions and remain viable. The central pattern that emerges from our\nstudies is that imperfect lesion repair often leads to increased mutational\nrobustness over semiconservative replication with completely efficient lesion\nrepair. The reason for this is that imperfect lesion repair breaks some of the\ncorrelation between the parent and daughter strands, thereby preventing\nreplication errors from destroying the information in the original genome. The\nresult is a delayed error catastrophe over that expected from the original\nsemiconservative quasispecies model. In particular, we show that when only of\nthe strands is necessary for conferring viability, then, when lesion repair is\nturned off, a semiconservatively replicating system becomes an effectively\nconservatively replicating one.",
"arxiv_id": "q-bio/0407004",
"authors": [
"Emmanuel Tannenbaum",
"James L. Sherley",
"Eugene I. Shakhnovich"
],
"categories": [
"q-bio.PE",
"q-bio.GN"
],
"title": "Semiconservative replication in the quasispecies model II: Generalization to arbitrary lesion repair probabilities",
"url": "https://arxiv.org/abs/q-bio/0407004"
},
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