Figure 1.
Structure and nucleotide position numbers follow Fullerton et al. [27] and Ensembl (ENSG00000130203). The location of primers used in this study are given above (forward primers) and below (reverse primers) the labeled exons. See Table S1 for primer and PCR-cycling information. An intronic SNP differentiating the two chimpanzee populations is highlighted in orange (position 2098*). SNP locations in red (3071 and 3073) represent putative APOE non-synonymous changes based on the chimpanzee genome assembly (Pan_troglodytes-2.1.4). Positions in blue (3205, 3937 and 4075) correspond to the amino acids (61, 112 and 158, respectively) that define the three human APOE alleles (E2, E3, E4). Position 4219† (in green) represents the single, synonymous difference between the P. t. verus sequences generated in this study and that of Fullerton et al. (2000) [27]. *corresponds to Ensembl coordinates 19∶45411002 for the human genome and 19∶50097633 for the chimpanzee genome. †corresponds to Ensembl coordinates 19∶45412223 for the human genome.
Table 1.
Variation at key APOE functional sites in Homo and Pan.
Figure 2.
Lineage-specific mutations mapped onto a schematic of the APOE protein (A) and primate phylogeny (B).
Protein structure is modeled after Bu 2009 [65], and tree topology represents known evolutionary relationships based on genome-wide data [46]. Human mutations [66] at key residues 61, 112 and 158 are in red. Including residue 61, the human APOE protein has four fixed, Homo-specific, non-synonymous mutations, all of which seem to be shared with the Denisovan hominin (inferred from reads mapped to the human genome at http://www.genome.ucsc.edu). The chimpanzee APOE protein is monomorphic within and between subspecies, and is identical to the bonobo APOE protein. Mutation R15H (dotted arrow) is shared by gorillas, chimpanzees and bonobos likely as a result of incomplete lineage sorting rather than independent evolution [46].