Cells rank genes by importance to protect them, according to new research

January 05, 2018

Researchers at the University of Oxford have discovered that a cellular mechanism preferentially protects plant genes from the damaging effects of mutation.

Whilst DNA sequence mutation is the fundamental fuel of species evolution, mutations in genes are often harmful. As a form of defence, organisms have evolved repair mechanisms to correct the DNA sequence following mutation. One of these mechanisms, is termed DNA mismatch repair (MMR). It corrects mutations that arise during the replication of the genome during cell division.

A new study, published in Genome Research, has shown for the first time that MMR is targeted to particular regions of the genome, and preferentially repairs genes.

The research was carried out in the Department of Plant Sciences, together with colleagues from Zhejiang University (China) and Lahore University of Management Studies (Pakistan).

Led by Oxford's Prof. Nicholas Harberd, the team looked at 9000 mutations accumulated in five generations of a MMR-deficient strain of the model plant species Arabidopsis thaliana, and compared them with mutations arising in an MMR-proficient strain.

The study has important implications for human health, and is particularly useful for understanding the changes that occur in cells during the development of the tumors that underlie cancers. MMR-deficiency predisposes cells to become tumorous, presumably because MMR-deficient cells lack the gene protection that reduces the risk of mutation in the genes that normally suppress tumor formation. The team have no plans to expand on these implications, but would welcome interest from anyone keen to follow up the study from a medical science perspective.

'As expected, the mutation rate in the MMR-deficient strain was massively higher than in the MMR-proficient strain', said Prof. Harberd. 'But we were surprised to see that whilst mutations are more or less randomly spread throughout the genome of the MMR-deficient strain, they are not randomly spread throughout the genome of the MMR-proficient strain.' In particular, genes, rather than non-genic regions of the genome, appeared to be preferentially protected from mutation in the MMR-proficient strain.

The paper finds that MMR preferentially repairs genes, rather than other regions of the genome. This finding significantly enhances our understanding of how organisms use MMR to reduce spontaneous mutation rates.

'Whilst genes are essential for the biology of organisms, the functions, if any, of the non-genic regions of the genome are less clear', said Prof. Harberd. 'It is therefore understandable that natural selection may have favored the relative targeting of MMR to genes rather than non-genic regions. The challenge now is to understand how that targeting works.'
-end-
Notes to editors:

The full paper citation is 'DNA mismatch repair preferentially protects genes from mutation' as featured in Genome Research, Written by Eric J. Belfield1,5, Zhong Jie Ding2,5, Fiona J.C. Jamieson1, Anne M. Visscher1,3, Shao Jian Zheng2, Aziz Mithani4 and Nicholas P. Harberd1

Web link: http://genome.cshlp.org/content/early/2017/12/11/gr.219303.116.abstract

For further information, please contact Lanisha Butterfield, Media Relations Manager on 01865 280531 or lanisha.butterfield@admin.ox.ac.uk

Image credit: Arabidopsis thaliana, the plant species used in this study' credit to Eric Belfield.

University of Oxford

Related Genome Articles from Brightsurf:

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Breakthrough in genome visualization
Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome.

Sturgeon genome sequenced
Sturgeons lived on earth already 300 million years ago and yet their external appearance seems to have undergone very little change.

A sea monster's genome
The giant squid is an elusive giant, but its secrets are about to be revealed.

Deciphering the walnut genome
New research could provide a major boost to the state's growing $1.6 billion walnut industry by making it easier to breed walnut trees better equipped to combat the soil-borne pathogens that now plague many of California's 4,800 growers.

Illuminating the genome
Development of a new molecular visualisation method, RNA-guided endonuclease -- in situ labelling (RGEN-ISL) for the CRISPR/Cas9-mediated labelling of genomic sequences in nuclei and chromosomes.

A genome under influence
References form the basis of our comprehension of the world: they enable us to measure the height of our children or the efficiency of a drug.

How a virus destabilizes the genome
New insights into how Kaposi's sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published Sept.

Better genome editing
Reich Group researchers develop a more efficient and precise method of in-cell genome editing.

Unlocking the genome
A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells.

Read More: Genome News and Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.