Abstract

The study of genomic divergence between humans and primates may provide insight into the origins of human beings and the genetic basis of unique human traits and diseases. Chromosome 21 is the smallest chromosome in the human genome, and some of its regions have been implicated in mental retardation and other diseases. In this study, we sequenced the coding and regulatory regions of 127 known genes on human chromosome 21 in DNA samples from human and chimpanzees and a part of the corresponding genes from orangutan, gorilla, and macaque. Overall, 3,003 nucleotide differences between human and chimpanzee were identified over approximately 400 kb. The differences in coding, promoter, and exon-intron junction regions were 0.51 +/- 0.02%, 0.88 +/- 0.03%, and 0.85 +/- 0.02%, respectively, much lower than the previously reported 1.23% in genomic regions, which suggests the presence of purifying selection. Significant variation in substitution rate among genes was observed by comparing the divergence between human and chimpanzee. Furthermore, by implementing a bioinformatics-based approach, we showed that the identification of genetic variants specific to the human lineage might lead to an understanding of the mechanisms that are attributable to the phenotypes that unique to humans, by changing the structure and/or dosage of the proteins expressed. A phylogenetic analysis unambiguously confirms the conclusion that chimpanzees were our closest relatives to the exclusion of other primates and the relative divergence of the Homo-Pan and that of (Homo-Pan)-Gorilla are 4.93 million years and 7.26 million years, respectively.