Structural and functional evolution of the TLR genes: a cross-species phylogenetic study and comparison with human oncogenes

Structural and functional evolution of the TLR genes: a cross-species phylogenetic study and comparison with human oncogenes

The toll-like receptors (TLRs) are transmembrane proteins of pattern recognition that play important roles in early innate immune recognition and in the orientation of adaptive immune response. The oncogenes found in tumours are mutant forms of normal functional genes (proto-oncogenes) that have a role in normal cell proliferation. In the current study, we aim to see whether in TLR genes of different species and human oncogenes there are relationships between phylogenetic distribution and structural / functional characteristics such as the ratio of GC/AT, the effective number of codon (ENC), codon adaptation index (CAI). The analysis included 62 mammalian TLR genes, 50 non-mammalian TLR genes and 120 human oncogenes. The results indicate: 1. Most TLR genes, either in mammal or non-mammal species, are AT-rich with low expressivity as indicated by their low CAI values, and most of these AT-rich TLR genes are located in gene-rich regions, which are commonly GC-rich sequences. 2. Significant codon usage bias only exists in a small number of the mammalian TLR genes, which are GC-rich and have a higher CAI values implicating a high expressivity. 3. In the 120 oncogenes analysed, 78 (65%) are GC-rich with higher expressivity (CAI: 0.40.06) than AT-rich oncogenes (CAI: 0.350.02, P<0.02). In addition, the GC-Rich oncogenes have a stronger codon usage bias (ENC: 40.35.9) than AT-Rich oncogenes genes (ENC: 48.9  3.51, P<0.01). 4. In the phylogenetic trees, the mammalian TLR genes from different organisms are located according to their function (orthologous genes), while non-mammalian TLR genes are distributed according to their host organism. 5. The phylogenetic relationship analysed on different portions of TLR genes indicated that the function-specific structures exist not only in the protein coding sequences, but also in the non-coding regions. Conclusion: In mammals, the evolution of TLR genes seems to be function-specific: orthologous TLR genes evolve within their functional category; while in non-mammals, the evolution of TLR genes is likely to be species-specific: the TLR genes within the same organism may evolve through duplication of a single phyletic lineage from their ancestor so that their structures share high similarities.

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