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Updated: Jun 21, 2026

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Why there is more to protein evolution than protein function: splicing, nucleosomes and dual-coding sequence.

Tobias Warnecke¹, Claudia C Weber, Laurence D Hurst

¹Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.

Biochemical Society Transactions

|July 21, 2009

Summary

Protein evolution rates vary due to more than just protein function. Selection during DNA and RNA production, particularly for splicing and DNA packaging, significantly impacts amino acid choice and evolutionary speed.

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Using the E1A Minigene Tool to Study mRNA Splicing Changes

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

Area of Science:

Evolutionary biology
Molecular biology
Genetics

Background:

Protein evolution rates exhibit significant variation.
Traditional views link evolutionary rates to functionally important sites and optimal amino acid function.
Existing models may be too simplistic, neglecting other evolutionary pressures.

Purpose of the Study:

To investigate factors beyond protein function that influence protein evolutionary rates.
To explore the impact of selection during protein production (DNA/RNA levels) on amino acid choice and evolution.
To assess the roles of splice site selection and nucleosome positioning in protein evolution.

Main Methods:

Review of existing evidence on selection pressures at DNA and RNA levels.
Analysis of how multiple coding demands constrain sequence evolution.
Comparative analysis of splicing-related constraints versus expression parameters in mammalian protein evolution.

Main Results:

Selection pressures during mRNA splicing (exonic splice enhancers) and DNA packaging (nucleosome positioning) affect amino acid choice.
Sequences with multiple coding requirements show heightened evolutionary constraint.
Splicing constraints are as important as expression parameters in predicting mammalian protein evolution rates.

Conclusions:

Protein evolutionary rates are influenced by selection acting during DNA and RNA processing, not solely by protein function.
The need to specify splice enhancers and ensure proper nucleosome positioning imposes significant constraints on protein evolution.
A more comprehensive understanding of protein evolution requires considering these production-related selection pressures alongside functional constraints.