Investigation On The Evolution Characteristics Of Human Tissue-Specific Genes

Based on the public databases, we investigate systematically the evolution features of the human tissue-specific genes which are involved in different places on the regulatory pathway, utilizing theories and methods of bioinformatics and evolutionary genomics. The work indicates that there exist the distinct evolution characteristics between the tissue-specific genes and the control. Further, we explore the underlying factors which may be the potential dynamics of the divergence in evolution rates. The presented work provides insight to the evolution selection of human tissue-specific genes, as well as new scenario for elucidating the potential evolutionary mechanism of corresponding genes.The main results are demonstrated as following:1) We examined different types of selection pressures [e.g. against amino acid mutations (Ka/Ks), against mutations at synonymous sites (Ks), against mutations at nonsynonymous sites (Ka)] by systemic analyses of human tissue-specific genes and their homologous genes in mouse. The results indicate that different classes of human tissue-specific genes involved in the regulatory pathway have divergent evolutionary rates. Similar to other tissue-specific genes, including signal transducers, nuclear receptors and neuroreceptors, tissue-specific transcription factors(Hox genes, non-Hox homeobox genes, HLH genes, Zinger finger genes) have on average lower value of Ka/Ks. However, the genes, including extracellular signals, signal receptors (Membrane-bound), neurotransmitters and other effectors, have the higher value of Ka/Ks.2) By calculating and comparing the values of Ks among all the classes of human tissue-specific genes, we find that the average synonymous rate does not exhibit the same magnitude of the average nonsynonymous substitution rate, illuminating that the mutation rate differences are not the main cause for the difference of selective constraints. The potential causes may underlie in the divergent function and expression.3) Compared to the cell-signaling and cell-division related genes, not all types of human tissue-specific genes evolve quickly. Apart from the Neurotransmitters and Signal receptors (Membrane-bound) genes, all the other tissue-specific genes have statistically lower value of Ka/Ks.4) We further identified and analyzed the transposable elements in the intronic regions of different genes. The results presented that the genes with lower evolution rates in coding regions have fewer density of transposable elements in intronic regions. It seems to imply that there exist potential correlation between the evolution of coding regions and corresponding intronic regions.In conclusion, in the paper, the divergent features and potential dynamics in evolution of human tissue-specific gene are detected and analyzed. The study provides a base clue and novel orientation for more profound investigations on evolution and divergence of tissue-specific genes.