"Waiting for regulatory sequences to appear"-review

The article "Waiting for regulatory sequences to appear" by Richard Durrett and Deena Schmidt investigates the time it takes for a new regulatory sequence to appear in a genome. Regulatory sequences are short sequences of DNA that bind to transcription factors, which are proteins that regulate the expression of genes. Mutations in regulatory sequences can change the way genes are expressed, which can lead to new traits or adaptations.

The authors use a mathematical model to study the time it takes for a new regulatory sequence to appear. They assume that the genome is a 1000-nucleotide region and that the new regulatory sequence is six to nine nucleotides long. They also assume that the new regulatory sequence must be at least 70% similar to a pre-existing regulatory sequence in order to be functional.

The authors find that the average waiting time for a new regulatory sequence to appear is 100,000 years. However, the waiting time can be much longer, depending on the mutation rate and the degree of similarity required for the new regulatory sequence to be functional. For example, if the mutation rate is very low, or if the new regulatory sequence must be very similar to a pre-existing regulatory sequence, the waiting time can be millions of years.

The authors conclude that the time it takes for new regulatory sequences to appear is a major factor in the rate of evolution. They argue that the long waiting times for new regulatory sequences can explain why some species evolve much more slowly than others.

The article "Waiting for regulatory sequences to appear" is a significant contribution to our understanding of the evolution of regulatory sequences. It provides a mathematical framework for studying the time it takes for new regulatory sequences to appear, and it suggests that the long waiting times for new regulatory sequences can be a major factor in the rate of evolution.

Here are some additional points from the article:

  • The authors also consider the case where the new regulatory sequence does not need to be perfectly matched to a pre-existing sequence. In this case, the waiting time is much shorter, on the order of 60,000 years.

  • The authors note that the waiting time for new regulatory sequences is likely to be even longer in real populations, because of the effects of natural selection. Natural selection will favor individuals with mutations that lead to new regulatory sequences that are beneficial. This will increase the mutation rate in the population, but it will also increase the waiting time for new regulatory sequences to appear.

  • The authors conclude that the waiting time for new regulatory sequences is a major constraint on the rate of evolution. They argue that this is one reason why some species evolve much more slowly than others.

Article snippets:


Waiting for regulatory sequences to appear

10.1214/105051606000000619

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?

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.

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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