**7. Summary**

The ORFs reported herein identified and characterized the vulture orthologues to TLR1 (CD281) and to IκBα, the first NF-κB pathway element from the griffon vulture *G. fulvus*. In addition, we have also identified sequences that may be involved in the protection of vul‐ tures against toxins. These results have implications for the understanding of the evolution of pathogen-host interactions. Particularly, these studies help to highlight a potentially im‐ portant regulatory pathway for the study of the related functions in vulture immune system (Perez de la Lastra & de la Fuente, 2007; 2008). Despite the overall structure of vulture TLR1 and expression pattern was similar to that of chicken, pig, cattle, human and mouse TLR, vulture TLR1 had differences in the length of the ectodomain, number and position of LRRs and N-glycosylation sites that makes vulture TLR1 structurally unique with possible func‐ tional implications.

Strong selective pressure for recognition of and response to pathogen-associated molecular patterns (PAMPs) has probably maintained a largely unchanged TLR signalling pathways in all vertebrates. The IκBα gene reported here expands our understanding of the immune reg‐ ulatory pathways present in carrion birds that are in permanent contact with pathogens. Current investigations should focus on the cloning and characterization of other members of NF-κB signalling cascade and genes controlled by this signalling pathway. At this point it is difficult to understand the implications of the structural differences between vulture TLR1, chicken TLR1 and TLR1 in different mammalian species. A greater understanding of the functional capacity of non-mammalian TLRs and, particularly in carrion birds that are in permanent contact with pathogens, has implications for the understanding of the evolution‐ ary pressures that defined the TLR repertoires in present day animals. The discovery of mol‐ ecules that neutralize toxins found in the genetic and phenotypic background of an organism (like vulture) is extremely adequate for bio compatible drugs and antidote devel‐ opment.

Consistent with the hypothesis that all these factors evolved from a common ancestral RHDankyrin structure within a unique superfamily, explaining the specificities of interaction be‐ tween the different Rel/NF-kappa B dimers and the various I kappa B inhibitors (Huguet, et

An Integrated View of the Molecular Recognition and Toxinology - From Analytical Procedures to Biomedical

Recently, the presence of two IkappaB-like genes in Nematostella encoded by loci distinct from nf-kb suggested that a gene fusion event created the nfkb genes in insects and verte‐ brates (Sullivan et al., 2007). This is consistent with the hypothesis that interactions between transcription factors of the Rel members and members of the IκB gene family evolved to reg‐ ulate genes mainly involved in immune inflammatory responses (Bonizzi & Karin, 2004).

NF-kappaB represents an ancient, generalized signaling system that has been co-opted for immune system roles independently in vertebrate and insect lineages (Friedman & Hughes, 2002). Therefore, while these proteins share a basic three-dimensional structure as predicted by their shared ankyrin repeat pattern and sequence, a possible evolutionary scenario based on this phylogenetic tree could be that subtle differences in the amino acid substitutions in the ankyrin repeats and flanking sequences occurred throughout evolution, which contrib‐

The ORFs reported herein identified and characterized the vulture orthologues to TLR1 (CD281) and to IκBα, the first NF-κB pathway element from the griffon vulture *G. fulvus*. In addition, we have also identified sequences that may be involved in the protection of vul‐ tures against toxins. These results have implications for the understanding of the evolution of pathogen-host interactions. Particularly, these studies help to highlight a potentially im‐ portant regulatory pathway for the study of the related functions in vulture immune system (Perez de la Lastra & de la Fuente, 2007; 2008). Despite the overall structure of vulture TLR1 and expression pattern was similar to that of chicken, pig, cattle, human and mouse TLR, vulture TLR1 had differences in the length of the ectodomain, number and position of LRRs and N-glycosylation sites that makes vulture TLR1 structurally unique with possible func‐

Strong selective pressure for recognition of and response to pathogen-associated molecular patterns (PAMPs) has probably maintained a largely unchanged TLR signalling pathways in all vertebrates. The IκBα gene reported here expands our understanding of the immune reg‐ ulatory pathways present in carrion birds that are in permanent contact with pathogens. Current investigations should focus on the cloning and characterization of other members of NF-κB signalling cascade and genes controlled by this signalling pathway. At this point it is difficult to understand the implications of the structural differences between vulture TLR1, chicken TLR1 and TLR1 in different mammalian species. A greater understanding of the functional capacity of non-mammalian TLRs and, particularly in carrion birds that are in permanent contact with pathogens, has implications for the understanding of the evolution‐ ary pressures that defined the TLR repertoires in present day animals. The discovery of mol‐

uted to their specificity of interaction with various members of the Rel family.

al., 1997).

Applications

260

**7. Summary**

tional implications.
