Differential Evolution of Antiretroviral Restriction Factors in Pteropid Bats as Revealed by APOBEC3 Gene Complexity

Hayward, Joshua A; Tachedjian, Mary; Cui, Jie; Cheng, Adam Z; Johnson, Adam; Baker, Michelle L; Harris, Reuben S; Wang, Lin-Fa; Tachedjian, Gilda

Many studies have indicated that A3 enzymes restrict endogenous transposable elements such as LINE-1 (long interspersed nuclear element 1) and Alu (Muckenfuss et al. 2006; Stenglein and Harris 2006; Kinomoto et al. 2007; Wissing et al. 2011 ). Interestingly, LINE-1 elements became extinct in the pteropid bat lineage approximately 24 Ma (Cantrell et al. 2008) . Preliminary dating of the A3 gene expansions (supplementary fig. S5 , Supplementary Material online) indicate that FIG. 5 . Hypermutation analysis of endogenized retroviruses reveals that ancient bat retroviruses were subjected to restriction by A3 proteins. (A) Comparison of guanine to adenine (G to A) versus cytosine to thymidine (C to T) mutations on the coding (þ) strand of endogenous retroviruses reveals strand-biased cytosine deamination. (B) Subsequent analysis of the dinucleotide context of the G to A mutations in the coding strand reveals that the GG to AG and GA to AA mutations typical of human A3G are the most common mutations in the endogenous retroviruses of bats. Statistical significance was calculated using Fisher's Exact Test. *P < 0.05; **P < 0.01; ***P < 0.001. Hayward et al. . doi:10.1093/molbev/msy048 MBE timing of the initial expansion of the bat A3Z1 subtype may coincide with this event and further investigation of a possible connection between pteropid A3 genes and the LINE-1 extinction may be warranted.