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Related Experiment Video

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Selection-dependent and Independent Generation of CRISPR/Cas9-mediated Gene Knockouts in Mammalian Cells

Selection-dependent and Independent Generation of CRISPR/Cas9-mediated Gene Knockouts in Mammalian Cells

Published on: June 16, 2017

Genomic selective constraints in murid noncoding DNA.

Daniel J Gaffney¹, Peter D Keightley

¹Institute of Evolutionary Biology, Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom. Daniel.Gaffney@mcgill.ca

|December 15, 2006

Summary

Mammalian genomes have significantly more functional noncoding DNA than coding DNA. Most constrained noncoding sites are intergenic, with developmental and neuronal genes having the most functional sites.

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Area of Science:

Genomics
Evolutionary Biology
Bioinformatics

Background:

Mammalian genomes contain numerous functional noncoding DNA sites.
Understanding selective constraint variation across noncoding DNA is crucial.

Purpose of the Study:

To estimate selective constraint in noncoding DNA compared to coding DNA in murid genomes.
To investigate the distribution and characteristics of constrained noncoding sites.

Main Methods:

Analysis of mouse-rat gene orthologs and surrounding noncoding DNA.
Estimation of selective constraint magnitudes.
Correlation analysis of intron properties and gene function.

Main Results:

Over three times more constrained noncoding sites than coding sites found in murids.
Majority of constrained noncoding sites located in intergenic regions (>5kb from genes).
Intron length and constraint negatively correlate with intron number; functional sites accumulate 5' to genes.
Developmental and neuronal genes show higher numbers of constrained noncoding sites than metabolic or electron transport genes.
Deleterious mutations in intergenic regions are twice those in genic regions.
Estimated total genomic deleterious point mutation rate is 0.91 per diploid genome per generation.

Conclusions:

Noncoding DNA plays a substantial role in mammalian genome function and evolution.
Functional noncoding elements are prevalent, particularly in intergenic regions and near specific gene types.
The distribution of functional intronic sites favors the 5' end of genes.
The estimated mutation rate in murids is higher than previously reported.