Table 2.
Amino acid changes that are fixed in present-day humans but ancestral in Neandertals. The table is sorted by Grantham scores (GS). Based on the classification proposed by Li et al. in (87), 5 amino acid substitutions are radical (>150), 7 moderately radical (101 to 150), 33 moderately conservative (51 to 100) and 32 conservative (1 to 50). One substitution creates a stop codon. Genes showing multiple substitutions have bold SwissProt identifiers. (Table S15 shows the human and chimpanzee genome coordinates, additional database identifiers, and the respective bases.) Genes with two fixed amino acids are indicated in bold.
| ID | Pos | AA | GS | Description/function |
|---|---|---|---|---|
| RPTN | 785 | */R | – | Multifunctional epidermal matrix protein |
| GREB1 | 1164 | R/C | 180 | Response gene in estrogen receptor–regulated pathway |
| OR1K1 | 267 | R/C | 180 | Olfactory receptor, family 1, subfamily K, member 1 |
| SPAG17 | 431 | Y/D | 160 | Involved in structural integrity of sperm central apparatus axoneme |
| NLRX1 | 330 | Y/D | 160 | Modulator of innate immune response |
| NSUN3 | 78 | S/F | 155 | Protein with potential SAM-dependent methyl-transferase activity |
| RGS16 | 197 | D/A | 126 | Retinally abundant regulator of G-protein signaling |
| BOD1L | 2684 | G/R | 125 | Biorientation of chromosomes in cell division 1-like |
| CF170 | 505 | S/C | 112 | Uncharacterized protein: C6orf170 |
| STEA1 | 336 | C/S | 112 | Metalloreductase, six transmembrane epithelial antigen of prostate 1 |
| F16A2 | 630 | R/S | 110 | Uncharacterized protein: family with sequence similarity 160, member A2 |
| LTK | 569 | R/S | 110 | Leukocyte receptor tyrosine kinase |
| BEND2 | 261 | V/G | 109 | Uncharacterized protein: BEN domain-containing protein 2 |
| O52W1 | 51 | P/L | 98 | Olfactory receptor, family 52, subfamily W, member 1 |
| CAN15 | 427 | L/P | 98 | Small optic lobes homolog, linked to visual system development |
| SCAP | 140 | I/T | 89 | Escort protein required for cholesterol as well as lipid homeostasis |
| TTF1 | 474 | I/T | 89 | RNA polymerase I termination factor |
| OR5K4 | 175 | H/D | 81 | Olfactory receptor, family 5, subfamily K, member 4 |
| SCML1 | 202 | T/M | 81 | Putative polycomb group (PcG) protein |
| TTL10 | 394 | K/T | 78 | Probable tubulin polyglutamylase, forming polyglutamate side chains on tubulin |
| AFF3 | 516 | S/P | 74 | Putative transcription activator, function in lymphoid development/oncogenesis |
| EYA2 | 131 | S/P | 74 | Tyrosine phosphatase, dephosphorylating “Tyr-142” of histone H2AX |
| NOP14 | 493 | T/R | 71 | Involved in nucleolar processing of pre-18S ribosomal RNA |
| PRDM10 | 1129 | N/T | 65 | PR domain containing 10, may be involved in transcriptional regulation |
| BTLA | 197 | N/T | 65 | B and T lymphocyte attenuator |
| O2AT4 | 224 | V/A | 64 | Olfactory receptor, family 2, subfamily AT, member 4 |
| CAN15 | 356 | V/A | 64 | Small optic lobes homolog, linked to visual system development |
| ACCN4 | 160 | V/A | 64 | Amiloride-sensitive cation channel 4, expressed in pituitary gland |
| PUR8 | 429 | V/A | 64 | Adenylsuccinate lyase (purine synthesis) |
| MCHR2 | 324 | A/V | 64 | Receptor for melanin-concentrating hormone, coupled to G proteins |
| AHR | 381 | V/A | 64 | Aromatic hydrocarbon receptor, a ligand-activated transcriptional activator |
| FAAH1 | 476 | A/G | 60 | Fatty acid amide hydrolase |
| SPAG17 | 1415 | T/A | 58 | Involved in structural integrity of sperm central apparatus axoneme |
| ZF106 | 697 | A/T | 58 | Zinc finger protein 106 homolog / SH3-domain binding protein 3 |
| CAD16 | 342 | T/A | 58 | Calcium-dependent, membrane-associated glycoprotein (cellular recognition) |
| K1C16 | 306 | T/A | 58 | Keratin, type I cytoskeletal 16 (expressed in esophagus, tongue, hair follicles) |
| LIMS2 | 360 | T/A | 58 | Focal adhesion protein, modulates cell spreading and migration |
| ZN502 | 184 | T/A | 58 | Zinc finger protein 502, may be involved in transcriptional regulation |
| MEPE | 391 | A/T | 58 | Matrix extracellular phosphoglycoprotein, putative role in mineralization |
| FSTL4 | 791 | T/A | 58 | Follistatin-related protein 4 precursor |
| SNTG1 | 241 | T/S | 58 | Syntrophin, gamma 1; binding/organizing subcellular localization of proteins |
| RPTN | 735 | K/E | 56 | Multifunctional epidermal matrix protein |
| BCL9L | 543 | S/G | 56 | Nuclear cofactor of beta-catenin signaling, role in tumorigenesis |
| SSH2 | 1033 | S/G | 56 | Protein phosphatase regulating actin filament dynamics |
| PEG3 | 1521 | S/G | 56 | Apoptosis induction in cooperation with SIAH1A |
| DJC28 | 290 | K/Q | 53 | DnaJ (Hsp40) homolog, may have role in protein folding or as a chaperone |
| CLTR2 | 50 | F/V | 50 | Receptor for cysteinyl leukotrienes, role in endocrine and cardiovascular systems |
| KIF15 | 827 | N/S | 46 | Putative kinesin-like motor enzyme involved in mitotic spindle assembly |
| SPOC1 | 355 | Q/R | 43 | Uncharacterized protein: SPOC domain containing 1 |
| TTF1 | 229 | R/Q | 43 | RNA polymerase I termination factor |
| F166A | 134 | T/P | 38 | Uncharacterized protein: family with sequence similarity 166, member A |
| CL066 | 426 | V/L | 32 | Uncharacterized protein: chromosome 12 open reading frame 66 |
| PCD16 | 763 | E/Q | 29 | Calcium-dependent cell-adhesion protein, fibroblasts expression |
| TRPM5 | 1088 | I/V | 29 | Voltage-modulated cation channel (VCAM), central role in taste transduction |
| S36A4 | 330 | H/R | 29 | Solute carrier family 36 (proton/amino acid symporter) |
| GP132 | 328 | E/Q | 29 | High-affinity G-protein couple receptor for lysophosphatidylcholine (LPC) |
| ZFY26 | 237 | H/R | 29 | Zinc finger FYVE domain-containing, associated with spastic paraplegia-15 |
| CALD1 | 671 | I/V | 29 | Actin- and myosin-binding protein, regulation of smooth muscle contraction |
| CDCA2 | 606 | I/V | 29 | Regulator of chromosome structure during mitosis |
| GPAA1 | 275 | E/Q | 29 | Glycosylphosphatidylinositol anchor attachment protein |
| ARSF | 200 | I/V | 29 | Arylsulfatase F precursor, relevant for composition of bone and cartilage matrix |
| OR4D9 | 303 | R/K | 26 | Olfactory receptor, family 4, subfamily D, member 9 |
| EMIL2 | 155 | R/K | 26 | Elastin microfibril interface-located protein (smooth muscle anchoring) |
| PHLP | 216 | K/R | 26 | Putative modulator of heterotrimeric G proteins |
| TKTL1 | 317 | R/K | 26 | Transketolase-related protein |
| MIIP | 280 | H/Q | 24 | Inhibits glioma cells invasion, down-regulates adhesion and motility genes |
| SPTA1 | 265 | N/D | 23 | Constituent of cytoskeletal network of the erythrocyte plasma membrane |
| PCD16 | 777 | D/N | 23 | Calcium-dependent cell-adhesion protein, fibroblasts expression |
| CS028 | 326 | L/F | 22 | Uncharacterized protein: chromosome 19 open reading frame 28 |
| PIGZ | 425 | L/F | 22 | Mannosyltransferase for glycosylphosphatidylinositol-anchor biosynthesis |
| DISP1 | 1079 | V/M | 21 | Segment-polarity gene required for normal Hedgehog (Hh) signaling |
| RNAS7 | 44 | M/V | 21 | Protein with RNase activity for broad-spectrum of pathogenic microorganisms |
| KR241 | 205 | V/M | 21 | Keratin-associated protein, formation of a rigid and resistant hair shaft |
| SPLC3 | 108 | I/M | 10 | Short palate, lung, and nasal epithelium carcinoma-associated protein |
| NCOA6 | 823 | I/M | 10 | Hormone-dependent coactivation of several receptors |
| WWC2 | 479 | M/I | 10 | Uncharacterized protein: WW, C2, and coiled-coil domain containing 2 |
| ASCC1 | 301 | E/D | 0 | Enhancer of NF-kappa-B, SRF, and AP1 transactivation |
| PROM2 | 458 | D/E | 0 | Plasma membrane protrusion in epithelial and nonepithelial cells |