Fig. 1: Mammalian BDNF exhibits overwhelmingly strict purifying selection, but also evidence of specific evolutionary pressures at particular sites. | Translational Psychiatry

Fig. 1: Mammalian BDNF exhibits overwhelmingly strict purifying selection, but also evidence of specific evolutionary pressures at particular sites.

From: The evolution of BDNF is defined by strict purifying selection and prodomain spatial coevolution, but what does it mean for human brain disease?

Fig. 1: Mammalian BDNF exhibits overwhelmingly strict purifying selection, but also evidence of specific evolutionary pressures at particular sites.

The FEL analysis of the BDNF gene found 174 of 261 (66.7%) sites to be statistically significant (LRT p value ≤ 0.1) for pervasive negative (purifying) selection. We plot the estimated values of omega (dN/dS) for each site in the alignment. Additionally, we plot 95% confidence intervals (CI) for each site. These results are also available in Table S1. We observe a high degree of strict purifying selection in the Human NGF region. The region for Human NGF corresponds to alignment sites 144–254 (NP_001700.2 and https://github.com/aglucaci/AnalysisOfOrthologousCollections/blob/main/tables/BDNF/BDNF_AlignmentMap.csv). This alignment of BDNF across all selected species (Mammalia, see Table 3) reveals a site-specific positive/adaptive diversifying selection and negative purifying selection. The thick line represents the point estimate (i.e., the evolutionary pressure) and the shadings reflect 95% confidence intervals which relate to the upper and lower bound of the point estimates. As shown, the prodomain sites exhibit more pervasive/episodic and positive/diversifying evolutionary selection, consistent with the fact that more disease-associated SNPs occur in this topological region of the BDNF gene in humans (early prodomain mapping not further shown due to nuanced variation across mammalian species).

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