Insights into the dN/dS ratio heterogeneity between brain specific genes and widely expressed genes in species of different complexity

• Brain-specific genes (BSGs) show lower dN/dS ratio than widely expressed genes (WEGs) in different species.
• Difference between dN/dS ratio of BSGs and WEGs increases as the complexity of the compared pair decreases.
• This difference in dN/dS ratio of BSGs and WEGs among diverse species supports the MGD theory over the universal molecular clock hypothesis.
• Being similar expression breadth of BSGs and WEGs, BSGs experience higher selection pressure due to higher expression level of BSG duplicates.
• Higher selection pressure on BSGs is also supported by their higher gene duplication frequency, multi-functionality, longer UTRs.

In mammals, it has long been suggested that brain-specific genes (BSGs) and widely expressed genes (WEGs) have seemingly lower dN/dS ratio than any other gene sets. However, to what extent these genes differ in their dN/dS ratio has still remained controversial. Here, we have revealed lower dN/dS ratio of BSGs than WEGs in human-mouse, human-orangutan, human-chimpanzee and mouse-rat orthologous pair. The significance level of dN/dS ratio difference indicates a trend of decreasing difference as complexity of compared pairs increases. Further studies with the human-mouse pair revealed that, removal of the duplicated genes from both the dataset has nullified this difference which dictates a vital role of duplicated genes in governing the selection pressure. Conclusively, higher paralog number, expression level, and longer regulatory region length of BSGs allow fewer nucleotide substitutions within them. Our results show for the first time to our knowledge lower dN/dS ratio of BSGs than WEGs.