Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection

Fisher, Colleen A.; Bhattarai, Eric K.; Osterstock, Jason B.; Dowd, Scot E.; Seabury, Paul M.; Vikram, Meenu; Whitlock, Robert H.; Schukken, Ynte H.; Schnabel, Robert D.; Taylor, Jeremy F.; Womack, James E.; Seabury, Christopher M.

To collectively estimate the extent of functional and/or selective constraint(s) related to bovine TLR protein function, we used a goodness of fit test to examine disparities between the observed distributions of AA phenotypes (PolyPhen + SIFT results; benign/ tolerated vs damaging/affect). Assuming equal probabilities for the occurrence of both classes of AA phenotypes across all bovine TLRs, we found there to be significantly fewer substitutions predicted to impact protein function than those classified as benign or tolerated (P = 0.00022). This is consistent with some degree of functional and/or selective constraints that generally operate to maintain the functional products of most protein coding genes [40] [41] [42] . However, this result describes a general trend across the bovine TLR gene family, and does not provide locus-specific insights regarding the evolutionary origin and magnitude of these constraints.