Mapping of chimpanzee full-length cDNAs onto the human genome unveils large potential divergence of the transcriptome

The genetic basis of the phenotypic difference between human and chimpanzee is one of the most actively pursued issues in current genomics. Although the genomic divergence between the two species has been described, the transcriptomic divergence has not been well documented. Thus, we newly sequenced and analyzed chimpanzee full-length cDNAs (FLcDNAs) representing 87 protein-coding genes. The number of nucleotide substitutions and sites of insertions/deletions (indels) was counted as a measure of sequence divergence between the chimpanzee FLcDNAs and the human genome onto which the FLcDNAs were mapped. Difference in transcription start/termination sites (TSSs/TTSs) and alternative splicing (AS) exons was also counted as a measure of structural divergence between the chimpanzee FLcDNAs and their orthologous human transcripts (NCBI RefSeq). As a result, we found that transposons (Alu) and repetitive segments caused large indels, which strikingly increased the average amount of sequence divergence up to more than 2% in the 3′-UTRs. Moreover, 20 out of the 87 transcripts contained more than 10% structural divergence in length. In particular, two-thirds of the structural divergence was found in the 3′-UTRs, and variable transcription start sites were conspicuous in the 5′-UTRs. As both transcriptional and translational efficiency were supposed to be related to 5′- and 3′-UTR sequences, these results lead to the idea that the difference in gene regulation can be a major cause of the difference in phenotype between human and chimpanzee.