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Genome-wide evidence of the importance of unusual DNA structures

5 July 2021
Appeared in BioNews 1102

Quadruple-stranded DNA structures appear to be evolutionarily conserved in some regions of the genome, indicating they serve an important purpose.

Most of a cell's DNA takes on the classical double-helix structure, but researchers at Pennsylvania State University have shown that one to 1.5 percent of the genome can also fold into quadruple-stranded DNA known as G-quadruplexes or G4s. 

'There have been only a handful of studies that provided experimental evidence for individual G4 elements playing functional roles,' said first author Dr Wilfried Guiblet. 'Our study is the first to look at G4s across the genome to see if they show the characteristics of functional elements as a general rule.'

The study, published in Genome Research, looked at the distribution of these structures and their stability at different points across the genome. The team found that G4s occur more frequently at sites regulating the function of genes and other elements, and that they are more stable when they form in these regions.

The research also revealed that the sequences of these structures are more evolutionarily conserved at these sites, suggesting they have been maintained through natural selection because they play an important role.

Study leader Dr YiFei Huang said: 'We can look at the patterns of change in a DNA sequence among human individuals and between humans and our close primate relatives as a test of natural selection and then use selection as an indicator of function.'

The findings represent a change in the way that scientists view the genome as a functional entity with the focus beginning to widen, encompassing not only protein-coding genes but also the way in which the structure of DNA affects its behaviour.

G4s were shown in the work to be important in parts of the genome controlling gene expression, DNA replication and within telomeres – the ends of chromosomes which are known to shorten with age. It has also been observed that they are more abundant in cancer cells.

The findings could enrich understanding of the genome and how some genes are differentially expressed in diseases such as cancer and neurological disorders, broadening the scope for treatments.

'The identification of G4s as novel functional elements within the human genome is key to advancing the use of genetics in precision medicine,' said co-author Professor Kristin Eckert.

SOURCES & REFERENCES
A new class of functional elements in the human genome?
Penn State News |  2 July 2021
Selection and thermostability suggest G-quadruplexes are novel functional elements of the human genome
Genome Research |  29 June 2021
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