Evolution of the glycophorin gene family in the hominoid primates

Analysis of nucleotide sequences of the human glycophorin A (GPA) and glycophorin B (GPB) genes has indicated that the GPA gene most closely resembles the ancestral gene, whereas the GPB gene likely arose from the GPA gene by homologous recombination. To study the evolution of the glycophorin gene family in the hominoid primates, restricted DNA on Southern blots from man, pygmy chimpanzee, common chimpanzee, gorilla, orangutan, and gibbon was probed with cDNA fragments encoding the human GPA and GPB coding and 3-untranslated regions. This showed the presence in all of the hominoid primates of at least one GPA-like gene. In addition, at least one GPB-like gene was detected in man, both chimpanzee species, and gorilla, strongly suggesting that the event that produced the GPB gene occurred in the common ancestor of man-chimpanzee-gorilla. An unexpected finding in this study was the conservation ofEcoRI restriction sites relative to those of the other four enzymes used; the significance of this observation is unclear, but raises the question of nonrandomness ofEcoRI restriction sites in noncoding regions. Further analysis of the evolution of this multigene family, including nucleotide sequence analysis, will be useful in clarification of the evolutionary relationships of the hominoid primates, in correlation with the structure and function of the glycophorin molecules, and in assessment of the role of evolution in the autogenicity of glycophorin determinants.This work was supported in part by National Institutes of Health Grants AM33463 and CA33000.     

Examination of hominid evolution by DNA sequence homology

Hominoid phylogeny was investigated in terms of unique DNA sequence homologies. In comparisons from the human standpoint the ΔTe₅₀ DNA values were Man 0, chimpanzee 0·7, gorilla 1·4, gibbon 2·7, orangutan 2·9, and African green monkey 5·7. In comparisons from the orangutan standpoint the ΔTe₅₀ DNA values were orangutan 0, chimpanzee 1·8, Man 1·9, gorilla 2·3, gibbon 2·4 and African green monkey 4·3. These results indicate that chimpanzee and gorilla are cladistically closer to Man than to orangutan and other primates, and that gorilla DNA may have diverged slightly more from the ancestral state than chimpanzee or human DNA. Comparisons from chimpanzee and gorilla DNA standpoints are needed to achieve a more definitive picture of hominoid phylogeny.     

Gorilla and orangutan c-myc nucleotide sequences: Inference on hominoid phylogeny

The nucleotide sequences of the gorilla and orangutan myc loci have been determined by the dideoxy nucleotide method. As previously observed in the human and chimpanzee sequences, an open reading frame (ORF) of 188 codons overlapping exon 1 could be deduced from the gorilla sequence. However, no such ORF appeared in the orangutan sequence.The two sequences were aligned with those of human and chimpanzee as hominoids and of gibbon and marmoset as outgroups of hominoids. The branching order in the evolution of primates was inferred from these data by different methods: maximum parsimony and neighborjoining.Our results support the view that the gorilla lineage branched off before the human and chimpanzee diverged and strengthen the hypothesis that chimpanzee and gorilla are more related to human than is orangutan. Correspondence to: F. Galibert     

Molecular evolution of IgG subclass among nonhuman primates: implication of differences in antigenic determinants among Apes

The cross-reactivity of five different rabbit polyclonal antibodies to human IgG and IgG subclass (IgG1, IgG2, IgG3, and IgG4) was determined by competitive ELISA with nine nonhuman primate species including five apes, three Old World monkeys, and one New World monkey. As similar to those previously reported, the reactivity of anti-human IgG antibody with plasma from different primate species was closely related with phylogenic distance from human. Every anti-human IgG subclass antibody showed low cross-reactivity with plasma from Old World and New World monkeys. The plasma from all apes except for gibbons (Hylobates spp.) showed 60 to 100% of cross-reactivity with anti-human IgG2 and IgG3 antibodies. On the other hand, chimpanzee (Pan troglodytes andPan paniscus) and orangutan (Pongo pygmaeus) plasma showed 100% cross-reactivity with anti-human IgG1 antibody, but gorilla (Gorilla gorilla) and gibbon plasma showed no cross-reactivity. The chimpanzee and gorilla plasma cross-reacted with anti-human IgG4 antibody at different reactivity, 100% in chimpanzee and 50% in gorilla, but no cross-reactivity was observed in orangutan and gibbon plasma. These results suggest the possibilities that the divergence of “human-type” IgG subclasses might occur at the time of divergence ofHomo sapience fromHylobatidae, and that the molecular evolution of IgG1 as well as IgG4 is different from that of IgG2 and IgG3 in great apes, this is probably caused by different in development of immune function in apes during the course of evolution.     

Gorilla society: What we know and don't know

Science is fairly certain that the gorilla lineage separated from the remainder of the hominoid clade about eight million years ago, 2 , 4 and that the chimpanzee lineage and hominin clade did so about a million years after that. 1 , 2 However, just this year, 2007, it was discovered that although the human head louse separated from the congeneric chimpanzee body louse (Pediculus) around the same time as the chimpanzee and hominin lineages split, 3 the human pubic louse apparently split from its sister species, the congeneric gorilla louse, Pthirus, 4.5 million years after their host lineages split. 3 No tested explanations exist for the discrepancy. Much is known about hominin evolution, but much remains to be discovered. The same is true of primate socioecology in general and gorilla socioecology in particular.     

Evolution of glycophorin A in the hominoid primates studied with monoclonal antibodies, and description of a sialoglycoprotein analogous to human glycophorin B in chimpanzee

Comparison of human and primate erythrocyte membrane sialoglycoproteins showed that common chimpanzee, dwarf chimpanzee, gorilla, orangutan, and gibbon have major periodic acid Schiff-positive proteins resembling human glycophorin A (GPA) monomer and dimer in electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels. Immunoperoxidase staining of Western blots with monoclonal antibodies to human GPA showed that these primate bands express some GPA antigenic determinants. A new sialoglycoprotein analogous to human glycophorin B (GPB) was detected in common chimpanzee. Although human MN blood group phenotype results from an amino acid polymorphism of GPA, Western blots showed that in chimpanzee sialoglycoprotein (GPAch) always expresses the M blood group, whereas chimpanzee sialoglycoprotein (GPBch) expresses either the N blood group or a null phenotype. This result explains the detection of M and MN, but not of N, blood group phenotypes in chimpanzee. GPBch has higher apparent m.w. than human GPB, is present in the erythrocyte membrane in greater quantity than human GPB, and contains trypsin cleavage site(s) and the 10F7 determinant (both found on human GPA but not GPB). Expression of human GPA antigenic determinants was consistent with the phylogeny of the hominoid primates; common and dwarf chimpanzee expressed most of the determinants tested, gorilla and orangutan an intermediate number, and gibbon and siamang the least. Of the GPA antigenic determinants examined, the MN blood group determinants were most consistently expressed during evolution of the hominoid primates. The results suggested that variability in expression of GPA antigenic determinants between species was due to both differences in amino acid sequence and glycosylation.     

UbC gene allele frequency in Korean population and novel UbC mosaic repeat unit formation

The genomic structural organization of human UbC CDS repeat units could be representative of concerted evolution. The structure of the UbC gene and its repeat unit number frequency at scales of different human ethnic populations remain to be sufficiently determined. In this study, we performed comparative analysis of UbC CDS regions in genomes from 140 Korean individuals. We found that the UbC gene allele types 9, 8 and 7 are present in the Korean population in proportions of 97.1%, 0.4% and 2.5%, respectively. Interestingly, we discovered that the allele types 7 and 8 harbor the novel UbC gene mosaic repeat units 3??5 (combined between sequence parts derived from standard repeat units 3 and 5) and 8??9 (combined between sequence parts derived from standard repeat units 8 and 9) within their sequence structures, respectively. Our analysis showed that the novel mosaic repeat unit 3^5 lacks the highly human-specific amino acid S38, implying a functional consequence. These results suggest that the genomic organization of UbC repeat units is still undergoing dynamic structural changes due to concerted evolution through unequal crossing-over. Our results could represent valuable data for future investigations related to treating genetic diseases caused by UbC gene mutations and variations.     

Characterization of a Novel Class of Interspersed LTR Elements in Primate Genomes: Structure, Genomic Distribution, and Evolution

Retrovirus-like sequences and their solitary (solo) long terminal repeats (LTRs) are common repetitive elements in eukaryotic genomes. We reported previously that the tandemly arrayed genes encoding U2 snRNA (the RNU2 locus) in humans and apes contain a solo LTR (U2-LTR) which was presumably generated by homologous recombination between the two LTRs of an ancestral provirus that is retained in the orthologous baboon RNU2 locus. We have now sequenced the orthologous U2-LTRs in human, chimpanzee, gorilla, orangutan, and baboon and examined numerous homologs of the U2-LTR that are dispersed throughout the human genome. Although these U2-LTR homologs have been collectively referred to as LTR13 in the literature, they do not display sequence similarity to any known retroviral LTRs; however, the structure of LTR13 closely resembles that of other retroviral LTRs with a putative promoter, polyadenylation signal, and a tandemly repeated 53-bp enhancer-like element. Genomic blotting indicates that LTR13 is primate-specific; based on sequence analysis, we estimate there are about 2,500 LTR13 elements in the human genome. Comparison of the primate U2-LTR sequences suggests that the homologous recombination event that gave rise to the solo U2-LTR occurred soon after insertion of the ancestral provirus into the ancestral U2 tandem array. Phylogenetic analysis of the LTR13 family confirms that it is diverse, but the orthologous U2-LTRs form a coherent group in which chimpanzee is closest to the humans; orangutan is a clear outgroup of human, chimpanzee, and gorilla; and baboon is a distant relative of human, chimpanzee, gorilla, and orangutan. We compare the LTR13 family with other known LTRs and consider whether these LTRs might play a role in concerted evolution of the primate RNU2 locus. Received: 29 September 1997 / Accepted: 16 January 1998     

Evolutionary origin of mutations in the primate cytochrome P450c21 gene.

The CYP21 gene codes for the enzyme cytochrome P450c21 (21-hydroxylase), which is critically involved in the synthesis of glucocorticoids and mineralocorticoids. Standard human haplotypes contain two copies of CYP21--a functional gene and a pseudogene. Inactivation of the functional gene leads to congenital adrenal hyperplasia (CAH). The pseudogene has three main defects: an 8-bp deletion in exon 3, a T insertion in exon 7, and a stop codon in exon 8. To determine the origin of these defects and to shed light on the evolution of the CYP21 gene, we sequenced relevant segments of 10 primate CYP21 genes--three from a chimpanzee, another three from a gorilla, and four from an orangutan. We could show that the 8-bp deletion is present in the chimpanzee and humans, while the other two defects are restricted to humans only. In the gorilla and the orangutan, however, extra CYP21 copies are inactivated by other defects so that the number of functional copies is reduced in each species. Comparison of the sequences has revealed evidence for intraspecific homogenization (concerted evolution) of the CYP21 genes, presumably through an expansion-contraction process effected by relatively frequent unequal but homologous crossing-over.     

Comparative mapping of human alphoid satellite DNA repeat sequences in the great apes

Heterochromatic regions of chromosomes contain highly repetitive, tandemly arranged DNA sequences that undergo very rapid variation compared to unique DNA sequences that are predominantly conserved. In this study the chromosomal basis of speciation has been looked at in terms of repeat sequences. We have hybridized twenty-one chromosome-specific human alphoid satellite DNA probes to metaphase spreads of the chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), and orangutan (Pongo pygmaeus) to investigate the evolutionary relationship of heterochromatic regions among such hominoid species. The majority of the probes did not hybridize to their corresponding equivalent chromosome but presented hybridization signals on non-corresponding chromosomes. Such observations suggest that rapid changes may have occurred in the ancestral alphoid satellite DNA sequence, resulting in divergence among the great ape species. This revised version was published online in July 2006 with corrections to the Cover Date.     

Molecular phylogeny and evolution of the human endogenous retrovirus HERV-W LTR family in hominoid primates

Long terminal repeats (LTRs) of human endogenous retrovirus (HERV) have contributed to the structural change or genetic variation of primate genome that are connected to speciation and evolution. Using genomic DNAs that were derived from hominoid primates (chimpanzee, gorilla, orangutan, and gibbon), we performed PCR amplification and identified thirty HERV-W LTR elements. These LTR elements showed a 82-98% sequence similarity with HERV-W LTR (AF072500). Specifically, additional sequences (GCCACCACCACTGTTT in the gorilla and TGCTGCTGACTCCCATCC in the gibbon) were noticed. Clone OR3 from the orangutan and clone GI2 from the gibbon showed a 100% sequence similarity, although they are different species. This indicates that both LTR elements were proliferated during the last 2 to 5 million years from the integration of the original LTR element. A phylogenetic tree that was obtained by the neighbor-joining method revealed a wide overlap of the LTR elements across species, suggesting that the HERV-W LTR family evolved independently during the hominoid evolution.     

人与大猩猩,黑猩猩和猩猩亲缘关系的探讨

有关人锆超科的系统发育仍然存在刍议。争论焦点在与大猩猩和黑猩猩哪 个关系更近一点。酪氨酸酶是黑色素合成中的关键酶,酪氨酶基因的突变将导致白化病。测定了人猿科中大猩猩,黑猩猩、猩猩和长臂锆产基因全部５个外显子的ＤＮＡ序列。     

Phylogenetic Analysis of a Retroposon Family in African Great Apes

The SINE-R retroposon family has been identified by its relationship with the long terminal repeats (LTRs) of human endogenous retrovirus class K (HERV-K) as a mobile element that has evolved recently in the human genome. Here we examined the recent evolutionary history of this class of elements by a PCR approach to genomic DNA from the African great apes and by phylogenetic analysis including comparison with the HERV K10 parent sequence. With primers derived from a cDNA sequence from human brain, we identified 27 sequences from the chimpanzee and 16 from the gorilla. Phylogenetic comparisons with previously recognized sequences from the human and from the orangutan and gibbon revealed wide overlap of elements across species, suggesting multiple origins in the course of hominoid evolution. Two human elements SINE-R.C2 and HS307 were the furthest removed from the HERV-K10 sequence but these two elements were closely related to three elements from the chimpanzee and four elements from the gorilla. This group of elements (our clusters 14 and 15) appears to have transposed late in hominoid evolution. One element (Ch-M16) showed 99.1% sequence identity with the SINE-R.C2 element, which is human-specific. Thus the SINE-R family appears to have continued to be active in transposition throughout the course of primate evolution. Received: 12 March 1999 / Accepted: 25 May 1999     

A comparison of TSPY genes from Y-chromosomal DNA of the great apes and humans: Sequence,evolution, and phylogeny

The genes for testis-specific protein Y (TSPY) were sequenced from chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), and baboon (Papio hamadryas). The sequences were compared with each other and with the published human sequence. Substitutions were detected at 144 of the 755 nucleotide positions compared. In overviewing five sequences, one deletion in human, four successive nucleotide insertions in orangutan, and seven deletions/insertions in baboon sequence were noted. The present sequences differed from that of human by 1.9% (chimpanzee), 4.0% (gorilla), 8.2% (orangutan), and 16.8% (baboon), respectively. The phylogenetic tree constructed by the neighbor-joining method suggests that human and chimpanzee are more closely related to each other than either of them is to gorilla, and this result is also supported by maximum likelihood and strict consensus maximum parsimony trees. The number of nucleotide substitutions per site between human and chimpanzee, gorilla, and orangutan for TSPY intron were 0.024, 0.048, and 0.094, respectively. The rates of nucleotide substitutions per site per year were higher in the TSPY intron than in the TSPY exon, and higher in the TSPY intron than in the ZFY (Zinc Finger Y) intron in human and apes. © 1996 Wiley-Liss, Inc.     

Morphometric analysis of hominoid lower molars from Yuanmou of Yunnan Province, China

Shape analyses of cross-sectional mandibular molar morphology, using Euclidean Distance Matrix Analysis, were performed on 79 late Miocene hominoid lower molars from Yuanmou of Yunnan Province, China. These molars were compared to samples of chimpanzee, gorilla, orangutan,Lufengpithecus lufengensis, Sivapithecus, Australopithecus afarensis, and human mandibular molars. Our results indicate that the cross-sectional shape of Yuanmou hominoid lower molars is more similar to the great apes that to humans. There are few differences between the Yuanmou,L. lufengensis, andSivapithecus molars in cross-sectional morphology, demonstrating strong affinities between these three late Miocene hominoids. All three of the fossil samples show strong similarities to orangutans. From this, we conclude that these late Miocene hominoids are more closely related to orangutants than to either the African great apes or humans.     

Regional localization of human M-BCR gene to chromosome 23 band q11 in the great apes

We hybridized a human M-BCR DNA probe to the chromosomes of chimpanzee (Pan troglodytes), gorilla (Gorilla gorilld) and orangutan (Pongo pygmaeus) by FISH-technique. The human M-BCR gene was localized to chromosome 23 band q11 (23q11), which is equivalent to the human chromosome 22 band q11 in all three species. The conservation of M-BCR gene in higher primates at the corresponding human chromosome locus provides phylogenetic clues concerning the evolution of genes.     

Evolution of subterminal satellite (StSat) repeats in hominids

Subterminal satellite (StSat) repeats, consisting of 32-bp-long AT-rich units (GATATTTCCATGTT(T/C)ATACAGATAGCGGTGTA), were first found in chimpanzee and gorilla (African great apes) as one of the major components of heterochromatic regions located proximal to telomeres of chromosomes. StSat repeats have not been found in orangutan (Asian great ape) or human. This patchy distribution among species suggested that the StSat repeats were present in the common ancestor of African great apes and subsequently lost in the lineage leading to human. An alternative explanation is that the StSat repeats in chimpanzee and gorilla have different origins and the repeats did not occur in human. The purpose of the present study was quantitative evaluation of the above alternative possibilities by analyzing the nucleotide variation contained in the repeats. We collected large numbers of sequences of repeat units from genome sequence databases of chimpanzee and gorilla, and also bonobo (an African great ape phylogenetically closer to chimpanzee). We then compared the base composition of the repeat units among the 3 species, and found statistically significant similarities in the base composition. These results support the view that the StSat repeats had already formed multiple arrays in the common ancestor of African great apes. It is thus suggested that humans lost StSat repeats which had once grown to multiple arrays.     

Evolution of DNA on Y-chromosome in hominoid primates as examined by PCR

Every species of non-human primates, especially those of hominoids, has a variety of reproductive structures and accompanying male traits, such as sexual dimorphism and relative size of testis to body weight, which may be at least partly triggered by DNA on the Y-chromosome. Recently, a panel of PCR (Polymerase Chain Reaction) primer sets were designed to amplify various DNA segments spread over the human Y-chromosome. We applied these primer sets for amplification of DNA segments on the Y-chromosome of hominoid species: chimpanzee, bonobo (Pygmy chimpanzee), gorilla, orangutan, whitehanded gibbon, agile gibbon, and Japanese monkey as an out group. The DNA segments including SRY, testis determining factor, and ZFX/ZFY could be amplified clearly in males of all species examined. These highly conserved genes may serve important biological functions. However, as the phylogenic distance from humans increased, some of the DNA segments could not be amplified. For example, DYZ1 (SY160) could be amplified only using human DNA as a template, and DYF60S1 (SY61), DYZ217 (SY126) and DYS233 (SY148) could be amplified only using human and African great ape DNA. It is interesting to note that locus DYS250 (SY17) could not be amplified in chimpanzee and bonobo but amplified in gorilla and orangutan. Locus DYS251 (SY18) was amplified in all species except the white-handed gibbon. These results indicate that a variety of evolutionary events including mutation, deletion, insertion, and rearrangement occurred in Y-chromosome DNA during primate evolution.     

Multiple recombinational events in primate immunoglobulin epsilon and alpha genes suggest closer relationship of humans to chimpanzees than to gorillas

Summary Immunoglobulin epsilon and alpha genes of chimpanzee and gorilla were isolated and their structures were compared with their human counterparts. Multiple deletions and duplications seem to have happened in both genes during hominoid evolution; the chimpanzee had deleted the entire C₂ gene after its divergence. In addition, the length of the C₁ hinge region of gorilla is distinct from those of chimpanzee and humans. Structural homology of the epsilon and alpha genes suggests that humans are evolutionarily closer to chimpanzees than to gorillas.     

Physical Mapping of Human 7q and 14q Subtelomeric DNA Sequences in the Great Apes

Phylogenetic divergence of the members of the Pongidae familyhas been based on genetic evidence. The terminal repeat array(T₂AG₃) has lately been considered as an additional basis toanalyze genomes of highly related species. The recent isolationof subtelomeric DNA probes specific for human (HSA) chromosomes7q and 14q has prompted us to cross-hybridize them to the chromosomesof the chimpanzee (PTR), gorilla (GGO) and orangutan (PPY) tosearch for its equivalent locations in the great ape species.Both probes hybridized to the equivalent telomeric sites ofthe long (q) arms of all three great ape species. Hybridizationsignals to the 7q subtelomeric DNA sequence probe were observedat the telomeres of HSA 7q, PTR 6q, GGO 6q and PPY 10q, whilehybridization signals to the 14q subtelomeric DNA sequence probewere observed at the telomeres of HSA 14q, PTR 15q, GGO 18qand PPY 15q. No hybridization signals to the chromosome 7-specificalpha satellite DNA probe on the centromeric regions of theape chromosomes were observed. Our observations demonstratesequence homology of the subtelomeric repeat families D7S427and D14S308 in the ape chromosomes. An analogous number of subtelomericrepeat units exists in these chromosomes and has been preservedthrough the course of differentiation of the hominoid species.Our investigation also suggests a difference in the number ofalpha satellite DNA repeat units in the equivalent ape chromosomes,possibly derived from interchromosomal transfers and subsequentamplification of ancestral alpha satellite sequences.