DNA damage repair system in C57BL/6 J mice is evolutionarily stable

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• The DNA damage repair (DDR) system is crucial for maintaining genome stability.
• Positive selection has been observed in human BRCA1/BRCA2 genes, but not extensively studied in other mammals.
• Previous studies on non-human mammals were limited by small sample sizes and focused mainly on BRCA genes.

Purpose of the Study:

• To investigate evolutionary selection pressures on DNA damage repair (DDR) genes in a non-primate mammal.
• To dynamically monitor genetic variation across 30 generations in the C57BL/6J mouse strain.
• To assess if DDR genes, beyond BRCA, are under positive selection in mammals.

Main Methods:

• Exome sequencing of 169 DDR genes from 44 C57BL/6J genomes (1998-2018).
• Comparison of coding sequences against historical C57BL/6J reference genomes (1998 and 2003).
• Analysis of genetic variation across 30 generations to detect evolutionary selection.

Main Results:

• No significant coding variations were found in Brca1, Brca2, or 167 other DDR genes over 30 generations.
• 812 coding variants were identified in 116 non-DDR genes, validating the analytical pipeline.
• The study found no evidence of positive selection acting on DDR genes in this mouse strain.

Conclusions:

• DNA damage repair (DDR) genes in the C57BL/6J mouse strain are not under positive selection.
• The findings suggest that the DDR system in rodents might be evolutionarily stable.
• This contrasts with observations in primates and warrants further investigation into mammalian DDR evolution.