How do mutations in gene regulatory DNA shape the fitness landscape?

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SUMMARY

Mutations in gene regulatory DNA significantly influence the fitness landscape, as detailed in Aviv Regev et al.'s 2022 paper in Nature. These mutations can be inherited or arise due to environmental factors, impacting gene expression and potentially leading to genetically associated diseases. The authors present a method for identifying regulatory DNA through sequence data analysis and evolutionary history, enabling predictions about the effects of mutations. This research has profound implications for medicine, agriculture, and the engineering of new life forms.

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TL;DR
Fitness landscapes are defined as the control (e.g., switch on/off) of protein coding DNA by regulatory (non-protein coding) DNA. Mathematical map modeling has improved our understanding of the landscape and its consequences.
Popular science version https://phys.org/news/2022-03-oracle-evolution-gene.html
Nature paper:
Aviv Regev, et al, "The evolution, evolvability and engineering of gene regulatory DNA", Nature (2022).

Abstract only because of paywall:
DOI: 10.1038/s41586-022-04506-6.
www.nature.com/articles/s41586-022-04506-6

The concept here is being able to interpret the maps in terms of predicting likelihoods of good/ bad results from changes DNA protein synthesis. There are several genetically associated diseases -- "bad results" -- mentioned in the pop sci article.

Mutations that occur in regulatory (non-coding) DNA play an important role in determining the fitness landscape. They may arise in the parent and are passed on to offspring, or arise in the individual -- both often occur as a result of environmental factors.

This is an example of 'Heredity Environment Interaction' that you learn about in freshman Biology. An often used example is phenotypic plasticity.
 
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In this paper, the authors describe a way to identify regulatory DNA by analyzing the sequence data and its evolutionary history. They then use this information to predict how changes in the regulatory DNA may affect gene expression, which can be used to understand the impact of mutations on the fitness landscape.

The implications of this work are quite exciting - the ability to predict outcomes from changes in genetic material could have important implications for medicine and agriculture. It could also allow us to better understand the underlying biology and evolution of organisms, and even help us engineer new life forms.
 

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