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Related Experiment Video

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Using the E1A Minigene Tool to Study mRNA Splicing Changes

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Published on: April 22, 2021

Genetic variation in mRNA coding sequences of highly conserved genes.

A L Ten Asbroek¹, J Olsen, D Housman

¹Neurozintuigen Laboratory, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.

Physiological Genomics

|April 4, 2001

Summary

Highly conserved human genes show less genetic polymorphism than disease genes, particularly in coding regions. This suggests strong selective pressure maintains sequence integrity in essential cellular functions.

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Area of Science:

Genomics
Molecular Biology
Evolutionary Biology

Background:

Understanding genetic polymorphism in the human genome is crucial.
Highly conserved genes, essential for DNA replication, transcription, and translation, are expected to have minimal sequence variation due to strong selective pressure.

Purpose of the Study:

To investigate the frequency and distribution of genetic polymorphism in highly conserved human genes.
To compare polymorphism levels in conserved genes with those in less conserved human disease genes.

Main Methods:

Analysis of the complete coding sequence and 3'-untranslated region (3'-UTR) of 22 highly conserved human genes.
Comparison of sequence variation data with studies on human disease genes.

Main Results:

Evolutionarily conserved genes exhibit lower average polymorphism than disease-related genes.
Reduced variation in conserved genes is primarily due to protein-coding sequences; noncoding regions show similar polymorphism levels.
The nature of polymorphism, including mutation spectrum and frequency, is comparable across gene types.

Conclusions:

Strong selective pressure on conserved genes minimizes nucleotide sequence polymorphism, especially in coding regions.
Noncoding regions of conserved genes show polymorphism levels similar to those in disease genes.
Conserved genes provide a baseline estimate for minimum sequence variation in the human genome.