At this post-genome age, we have already known that human has quite similar genome compared to its closest extant cousin, chimpanzee. It had been proposed that the changes at the regulation level rather than at the protein coding sequence level play more important roles during human evolution. In this study, we focused on the genes that are conserved among human, chimpanzee and rhesus macaques, and examined the ones that possibly went through positive selection on gene expression regulation in human. Interestingly, our study revealed one previously un-characterized gene cluster TMEM159-ZP2-CRYM that is specifically regulated in the human genome. The genes in this cluster show dramatic age-related changes in human cerebellum, specifically, they are co-up regulated at early human cerebellum post-natal developmental stage and keep their high expression levels to the whole later life span.  To carry out this inter-species gene expression comparison, we had developed a new method named BITS, which is based on high-throughput transcriptome sequencing data and can estimate the gene expression level for different species in more conserved and balanced way. Based on BITS method, we observed significant divergence to diversity ratio difference between protein-coding genes and pseudogenes as well as more species-specific up-regulated genes in human brain areas than in non-brain tissues. This study could be valuable for further functional study of human specific features as well as inter-species gene expression comparison. Finally, we show that the down-regulation of TMEM159-ZP2-CRYM is correlated with several human diseases, which might indicate their important functions in human cerebellum.

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