Waiting for regulatory sequences to appear

DOI10.1214/105051606000000619MaRDI QIDQ2467108zbMATH OpenOpenAlexFDO

Authors Richard Durret, Deena R. Schmidt

Publication date 18 January 2008

Published in The Annals of Applied Probability (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/math/0702883

zbMATH Keywords

population geneticsPoisson approximationMoran modelChen-Stein calculationsclumping heuristic

Mathematics Subject Classification ID

Applications of Markov chains and discrete-time Markov processes on general state spaces (social mobility, learning theory, industrial processes, etc.) (60J20) Genetics and epigenetics (92D10) Problems related to evolution (92D15) Protein sequences, DNA sequences (92D20) Central limit and other weak theorems (60F05) Computational methods for problems pertaining to biology (92-08)

Abstract: One possible explanation for the substantial organismal differences between humans and chimpanzees is that there have been changes in gene regulation. Given what is known about transcription factor binding sites, this motivates the following probability question: given a 1000 nucleotide region in our genome, how long does it take for a specified six to nine letter word to appear in that region in some individual? Stone and Wray [Mol. Biol. Evol. 18 (2001) 1764--1770] computed 5,950 years as the answer for six letter words. Here, we will show that for words of length 6, the average waiting time is 100,000 years, while for words of length 8, the waiting time has mean 375,000 years when there is a 7 out of 8 letter match in the population consensus sequence (an event of probability roughly 5/16) and has mean 650 million years when there is not. Fortunately, in biological reality, the match to the target word does not have to be perfect for binding to occur. If we model this by saying that a 7 out of 8 letter match is good enough, the mean reduces to about 60,000 years.

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Cites work

• scientific article; zbMATH DE number 5819433 (Why is no real title available?)
• scientific article; zbMATH DE number 3540347 (Why is no real title available?)
• scientific article; zbMATH DE number 2070281 (Why is no real title available?)
• scientific article; zbMATH DE number 1761225 (Why is no real title available?)
• Lower bounds for covering times for reversible Markov chains and random walks on graphs
• Mathematical population genetics. I: Theoretical introduction.
• Probability approximations via the Poisson clumping heuristic
• Two moments suffice for Poisson approximations: The Chen-Stein method

Cited in

(5)

• Using statistical methods to model the fine-tuning of molecular machines and systems
• On the waiting time until coordinated mutations get fixed in regulatory sequences
• OPTIMAL CONTROL OF GENETIC DIVERSITY IN THE MORAN MODEL WITH POPULATION GROWTH
• A stochastic model for the evolution of transcription factor binding site abundance
• A waiting time problem arising from the study of multi-stage carcinogenesis

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