Bounds on identification of genome evolution pacemakers

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Several works have pointed out that the tight correlation between genes’ evolutionary rate is better explained by a model denoted as the Universal Pacemaker (UPM) rather than by a simple rate constancy as manifested by the classical hypothesis of Molecular Clock (MC). Under UPM, the relative evolutionary rates of all genes remain nearly constant whereas the absolute rates can change arbitrarily according to the pacemaker ticks. This evolutionary framework was recently adapted to model epigenetic aging where methylated sites are the analogs of evolving genes. A consequent question to the above finding is the determination of the number of such pacemakers and which gene adheres to which pacemaker. This however turns to be a non trivial task and is affected by the number of variables, their random noise, and the amount of available information. To this end, a clustering heuristic was devised exploiting the correlation between corresponding edge lengths across thousands of gene trees. Nevertheless, no theoretical study linking the relationship between the affecting parameters was done. We here study this question by providing theoretical bounds, expressed by the system parameters, on probabilities for positive and negative results. We corroborate these results by a simulation study that reveals the critical role of the variances.

Original languageEnglish
Title of host publicationBioinformatics Research and Applications - 14th International Symposium, ISBRA 2018, Proceedings
EditorsFa Zhang, Shihua Zhang, Zhipeng Cai, Pavel Skums
PublisherSpringer Verlag
Number of pages12
ISBN (Print)9783319949673
StatePublished - 2018
Event14th International Symposium on Bioinformatics Research and Applications, ISBRA 2018 - Beijing, China
Duration: 8 Jun 201811 Jun 2018

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume10847 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349


Conference14th International Symposium on Bioinformatics Research and Applications, ISBRA 2018

Bibliographical note

Publisher Copyright:
© Springer International Publishing AG, part of Springer Nature 2018.


  • Gene partitioning
  • Phylogenetics
  • Probabilistic geometrical clustering
  • Universal Pacemaker

ASJC Scopus subject areas

  • Theoretical Computer Science
  • General Computer Science


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