Evolutionary relationship ofHLA-DRB genes inferred from intron sequences

The major histocompatibility complex (Mhc) consists of class I and class II genes. In the humanMhc (HLA) class II genes, nineDRB loci have been identified. To elucidate the origin of these duplicated loci and allelic divergences at the most polymorphicDRBI locus, introns 4 and 5 as well as the 3′ untranslated region (altogether approximately 1,000 base pairs) of sevenHLA-DRB loci, threeHLA-DRBI alleles, and nine nonhuman primateDRB genes were examined. It is shown that there were two major diversification events inHLA-DRB genes, each involving gene duplications and allelic divergences. Approximately 50 million years (my) ago,DRBI ^*04 and an ancestor of theDRB1 ^*03 cluster (DRBI ^*03, DRBI^*15, andDRB3) diverged from each other andDRB5, DRB7, DRB8, and an ancestor of theDRB2 cluster (DRB2, DRB4, andDRB6) arose by gene duplication. Later, about 25 my ago,DRBI ^*15 diverged fromDRBI*03, andDRB3 was duplicated fromDRBI ^*03. Then, some 20 my ago, the lineage leading to theDRB2 cluster produced two new loci,DRB4 andDRB6. TheDRBI ^*03 andDRBI ^*04 allelic lineages are extraordinarily old and have persisted longer than some duplicated genes. The orthologous relationships ofDRB genes between human and Old World monkeys are apparent, but those between Catarrhini and New World monkeys are equivocal because of a rather rapid expansion and contraction of primateDRB genes by duplication and deletion. Correspondence to: Y. Satta     

Structure and organization of pigMHC class IIDRB genes: evidence for genetic exchange between loci

The pig major histocompatibility complexDRB genes were studied by polymerase chain reaction (PCR) amplification of exon 2 from eight domestic pigs and two European wild boars. Sequence comparisons together with a phylogenetic analysis showed the existence of at least threeDRB genes of which only one appears to be expressed. The two putativeDRB pseudogenes contained delections in exon 2, making it possible to confirm the presence of three non-allelicDRB genes by analyzing the length polymorphism of the amplified PCR products. The expressed gene shows allelic polymorphism at the same positions as in the humanDRB1 gene. In addition this pig gene shows extensive allelic polymorphism at positions 84–88, whereas, e.g., humanDRB genes do not. Surprisingly, the the two putativeDRB pseudogenes also display a considerable amount of allelic polymorphism, albeit of a different character as compared with the expressedDRB gene. Short stretches of sequences are shared between individual alleles at different loci. These sequence similarities cannot be due to natural selection, since two of the threeDRB genes involved are polymorphic pseudogenes constituting allelic series that have diverged after the inactivation event. Instead, the results indicate that the sequences have been exchanged between theDRB genes by intergenic recombination. The nucleotide sequence data reported in this paper have been submitted to the EMBL/GenBank nucleotide sequence databases and have been assigned the accession numbers L36567 (DRB1 ^* 1) L36568 (DRB1 ^* 2), L36569 (DRB1 ^* 3), L36570 (DRB1 ^* 4), L36571 (DRB1 ^* 5), L36572 (DRB1 ^* 6), L36573 (DRB1 ^* 7), L36574 (DRB1 ^* 8), L36575 (DRB2 ^* 1), L36576 (DRB2 ^* 2A), L36577 (DRB2 ^* 2B), L36578 (DRB2 ^* 2C), L36579 (DRB1 ^* 2D), L36580 (DRB2 ^* 3), L36581 (DRB2 ^* 4), L36582 (DRB3 ^* 1A), L36583 (DRB3 ^* 1B), L36584 (DRB3 ^* 1C), L36585 (DRB3 ^* 1D)     

Transcription and diversity of immunoglobulin lambda chain variable genes in the rat

The DRB region of the human major histocompatibility complex displays length polymorphism: Five major haplotypes differing in the number and type of genes they contain have been identified, each at appreciable frequency. In an attempt to determine whether this haplotype polymorphism, like the allelic polymorphism, predates the divergence of humansfrom great apes, we have worked out the organization of the DRB region of the chimpanzee Hugo using a combination of chromosome walking, pulsed-field gel electrophoresis, and sequencing. Hugo is a DRB homozygote whose single DRB haplotype is some 440 kilobases (kb) long and contains five genes. At least one and possibly two of these are pseudogenes, while three are presumably active genes. The genes are designated DRB ^* A0201, DRB2 ^* 0101, DRB3 ^* 0201, DRB6 ^* 0105, and DRB5 ^* 0301, and are arranged in this order on the chromosome. The DRB2 and DRB3 genes are separated by approximately 250 kb of sequence that does not seem to contain any additional DRB genes. The DRB ^* A0201 gene is related to the DRB1 gene of the human DR2 haplotype; the DRB2 ^* 0101 and DRB3 ^* 0201 genes are related to the DRB2 and DRB3 genes of the human DR3 haplotype, respectively; the DRB6 ^* 0105 and DRB5 ^* 0301 genes are related to the DRBVI and DRB5 genes of the human DR2 haplotype, respectively. Thus the Hugo haplotype appears to correspond to the entire human DR2 haplotype, into which a region representing a portion of the human DR3 haplotype has been inserted. Since other chimpanzees have their DRB regions organized in different ways, we conclude that, first, the chimpanzee DRB region, like the human DRB region, displays length polymorphism; second, some chimpanzee DRB haplotypes are longer than the longest known human DRB haplotypes; third, in some chimpanzee haplotypes at least, the DRB genes occur in combinations different from those of the human haplotypes; fourth, and most importantly, certain DRB gene combinations have been conserved in the evolution of chimpanzees and humans from their common ancestors. These data thus provide evidence that not only allelic but also haplotype polymorphism can be passed on from one species to another in a given evolutionary lineage.     

Mhc-DRB Genes and the Origin of New World Monkeys

The major histocompatibility complex (Mhc) is a family of loci characterized by its relatively rapid evolutionary turnover, large genetic distances between genes, and long persistence of allelic lineages effected by balancing selection. These features render the Mhc highly suitable for answering questions concerning speciation and adaptive radiation. The aim of the present study was to use Mhc-DRB genes to make inferences about the founding population of the Platyrrhini. Three segments, each approximately 300 base pairs in length, of the platyrrhine DRB genes were amplified by the polymerase chain reaction and sequenced. The segments were derived from intron 2, exon 3, and exon 6 of DRB genes from different species of New World monkeys. The results of the study have revealed that on a phylogenetic tree, all of the tested platyrrhine genes appear to form a single cluster, while all catarrhine DRB genes form a distinct cluster, although the bootstrap values fail to provide statistically significant support for the separation of these two clades. This observation suggests that the multiple platyrrhine genes originated from a single ancestral gene after the divergence of the Platyrrhini and Catarrhini and thus contradicts the results of an earlier study in which some exon 2 DRB sequences appeared to predate the split of the two primate groups. The inconsistency in the DRB gene phylogeny can be explained by postulating convergent evolution for the peptide-binding region of the DRB exon 2 sequences. The phylogeny of the platyrrhine DRB genes (except for exon 2) is relatively "shallow"; the distances between genes are relatively short (in comparison to the catarrhine DRB genes), and there is a tendency for sequences of individual species to cluster together. The phylogeny of the platyrrhine DRB genes is consistent with the postulate that a small population founded the group and that there is an ongoing adaptive radiation from small, relatively isolated founding populations.     

Primate DRB genes from the DR3 and DR8 haplotypes contain ERV9 LTR elements at identical positions

The HLA-DRB genes of the human major histocompatibility complex constitute a multigene family with a varying number of DRB genes in different haplotypes. To gain further knowledge concerning the evolutionary relationship, the complete nucleotide sequence was determined for a region spanning introns 4 and 5 of the three DRB genes (DRB1*0301, DRB2 and DRB3*0101) from a DR52 haplotype and the single DRB gene (DRB1*08021) in the DR8 haplotype. These analyses identified an endogenous retroviral long terminal repeat element (ERV9 LTR3), inserted at identical positions in intron 5 of the functional DRB genes in these two haplotypes. Comparison of the nucleotide sequence from introns 4 and 5 including the ERV9 LTR elements revealed a strong similarity between the three expressed DRB genes. The DRB3*0101 and DRB1*08021 genes were most similar in this comparison. These findings provide further evidence for a separate duplication in a primordial DR52 haplotype followed by a gene contraction event in the DR8 haplotype. A homologous element was found in a chimpanzee DRB gene from a DR52 haplotype. This represents the first characterized ERV9 LTR element in a nonhuman species. The corresponding introns of the DRB genes in the DR4 haplotype contain no ERV9 LTRs. In contrast, these genes have insertions of distinct Alu repeats, implying distinct evolutionary histories of DR52 and DR53 haplotypes, respectively. Phylogenetic analyses of DRB introns from DR52, DR53, and DR8 haplotypes showed a close relationship between the DRB2 and DRB4 genes. Thus, the ancestral DR haplotype that evolved to generate the DR52 and DR53 haplotypes most likely shared a primordial common DRB gene.The nucleotide sequence data reported in this paper have been submitted to the EMBL nucleotide sequence database and have been assigned the accession numbers X82660–X82663     

Identification of MhcMafa-DRB Alleles in a Cohort of Cynomolgus Macaques of Vietnamese Origin

Cynomolgus macaques have been used widely to build a research model of infectious and chronic diseases, as well as in transplantation studies, where disease susceptibility and/or resistance are associated with the major histocompatibility complex (MHC). To better elucidate polymorphisms and genetic differences in the Mafa‐DRB locus, and facilitate the experimental use of cynomolgus macaques, we used pool screening combined with cloning and direct sequencing of polymerase chain reaction products to characterize MhcMafa‐DRB gene alleles in 153 Vietnamese cynomolgus macaques. We identified 30 Mafa‐DRB alleles belonging to 17 allelic lineages, including four novel sequences that had not been documented in earlier reports. The highest frequency allele was Mafa‐DRB*W27:04, which was present in 7 of 35 (20%) monkeys. The next most frequent alleles were Mafa‐DRB*3:07 and Mafa‐DRB*W7:01, which were detected in 5 of 35 (14.3%) and 4 of 35 (11.4%) of the monkeys, respectively. The high‐frequency alleles in this Vietnamese population may be high priority targets for additional characterization of immune functions. Only the DRB1*03 and DRB1*10 lineages were also present in humans, whereas the remaining alleles were monkey‐specific lineages. We found 25 variable sites by aligning the deduced amino acid sequences of 29 identified alleles. Evolutionary and population analyses based on these sequences showed that human, rhesus, and cynomolgus macaques share several Mhc‐DRB lineages and the shared polymorphisms in the DRB region may be attributable to the existence of interbreeding between rhesus and cynomolgus macaques. This information will promote the understanding of MHC diversity and polymorphism in cynomolgus macaques and increase the value of this species as a model for biomedical research. Am. J. Primatol. 74:958‐966, 2012. © 2012 Wiley Periodicals, Inc.     

Convergent evolution of major histocompatibility complex molecules in humans and New World monkeys

  In both Old World and New World monkeys Mhc-DRB sequences have been found which resemble human DRB1*03 and DRB3 genes in their second exon. The resemblance is shared sequence motifs and clustering of the genes or the encoded proteins in phylogenetic trees. This similarity could be due to common ancestry, convergence at the molecular level, or chance. To test which of these three explanations applies, we sequenced segments of New World monkey and macaque genes which encompass the entire second exon and large parts of both flanking introns. The test strongly supports the monophyly of New World monkey DRB intron sequences. The phylogenies of introns 1 and 2 from DRB1*03-like and DRB3-like genes are congruent, but both are incongruent with the exon 2-based phylogeny. The matching of intron 1- and intron 2-based phylogenies with each other suggests that reciprocal recombination has not played a major role in exon 2 evolution. Statistical comparisons of exon 2 from different DRB1*03 and DRB3 lineages indicate that it was neither gene conversion (descent), nor chance, but molecular convergence that has shaped their characteristic motifs. The demonstration of convergence in anthropoid Mhc-DRB genes has implications for the classification, age, and mechanism of generation of DRB allelic lineages. Received: 30 August 1999 / Revised: 19 October 1999     

Evolution of the Sweetness Receptor in Primates. II. Gustatory Responses of Non-human Primates to Nine Compounds Known to be Sweet in Man

The gustatory responses of nine compounds, namely glycine, D-phenylalanine,D-tryptophan, cyanosuosan, magapame, sucrononate, campame, cyclamateand superaspartame, all known as sweet in man, were studiedin 41 species or subspecies of non-human primates, selectedamong Prosimii (Lemuridae and Lorisidae), Platyrrhini (Callitrichidaeand Cebidae) and Catarrhini (Cercopithecidae, Hylobatidae andPongidae). The first six compounds are generally sweet to allprimates, which implies that they interact with the primatesweetness receptors essentially through constant recognitionsites. Campame is sweet only to Cebidae and Catarrhini, cyclamateonly to Catarrhini, superaspartame principally to Callitrichidaeand Catarrhini, which implies that all these compounds interactwith the receptors partly through variable recognition sites.From the present work, from other previous results (where notablyit was observed that alitame is sweet to all primates, ampameonly to Prosimii and Catarrhini, and aspartame only to Catarrhini),and from the multipoint attachment (MPA) theory of sweetnessreception (as elaborated by Nofre and Tinti from a detailedstudy of structure-activity relationships of various sweetenersin man), it is inferred that the primate sweetness receptorsare very likely made up of eight recognition sites, of whichthe first, second, third, fourth, seventh and eighth are constant,and the fifth and sixth variable. From these results and fromthe MPA theory, it is also inferred that the recognition sitesof the primate sweetness receptors could be: Asp-1 or Glu-1,Lys-2, Asp-3 or Glu-3, Thr-4, X-5, X-6, Thr-7, Ser-8, wherethe variable recognition sites X-5 and X-6 would be: Ala-5 andAla-6 for Callitrichidae, Ser-5 and Ala-6 for Cebidae, Ala-5and Thr-6 for Prosimii, and Thr-5 and Thr-6 for Catarrhini.By using Tupaiidae (tree shrews) as a reference outgroup andby means of other structural and functional molecular considerations,it appears that Callitrichidae have retained the most primitivereceptor among the four types of primate receptors. The possibletaxonomic and phylogenetic implications of these findings arediscussed. Chem. Senses 21: 747–762, 1996.     

Hypervariability of intronic simple (gt)n(ga)m repeats in HLA-DRB genes

We have investigated the extent of DNA variability in intronic simple (gt)_n(ga)_m repeat sequences and correlated this to sequence polymorphisms in the flanking exon 2 of HLA-DRB genes. The polymerase chain reaction (PCR) was used to amplify a DNA fragment containing exon 2 and the repeat region of intron 2. The PCR products were separated on sequencing gels in order to demonstrate length hypervariability of the (gt)_n(ga)_m repeats. In a parallel experiment, the PCR products were cloned and sequenced (each exon 2 plus adjacent simple repeats) to characterize the simple repeats in relation to the HLA-DRB sequences. In a panel of 25 DRB1, DRB4, and DRB5 alleles new sequences were not detected. Restriction fragment length polymorphism (RFLP) subtyping of serologically defined haplotypes corresponds to translated DNA sequences in 85% of the cases, the exceptions involving unusual DR/DQ combinations. Many identical DRB1 alleles can be distinguished on the basis of their adjacent simple repeats. We found group-specific organization of the repeats: the DRw52 supergroup repeats differ from those of DRB1*0101, DRB4*0101, and DRB5*0101 alleles and from those of pseudogenes. Finally, we amplified baboon DNA and found a DRB allele with extensive similarity to DRB1 sequences of the DRw52 supergroup. The simple repeat of the baboon gene, however, resembles that of human pseudogenes. In addition to further subtyping, the parallel study of polymorphic protein and hypervariable DNA alleles may allow conclusions to be drawn on the relationships between the DRB genes and perhaps also on the theory of trans-species evolution.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M 34258.     

Diversity associated with the second expressed H L A - D R B locus in the human population

Although diversity within the HLA-DRB region is predominantly focused in the DRB1 gene, the second expressed DRB loci, DRB3, DRB4, and DRB5, also exhibit variation. Within DRB1 ^* 15 or DRB1 ^* 16 haplotypes, four new variants were identified: 1) two new DRB5 alleles, DRB5 ^* 0104 and DRB5 ^* 0204, 2) a haplotype carrying a DRB1 ^* 15 or ^* 16 allele without the usual accompanying DRB5 allele, and 3) a haplotype carrying a DRB5^* 0101 allele without a DRB1 ^* 15 or ^* 16 allele. The evolutionary origins of these haplotypes were postulated based on their associations with the DRB6 pseudogene. Within HLA haplotypes which carry DRB3, a new DRB3 ^* 0205 allele and one unusual DRB3 association were identified. Finally, two new null DRB4 alleles are described: DRB4 ^* 0201N, which exhibits a deletion in the second exon, and a second allele, DRB4 ^* null, which lacks the second exon completely. Gene conversion-like events and variation in the number of functional genes through reciprocal recombination and inactivation contribute to the diversity observed in the second expressed HLA-DRB loci. Received: 2 November 1996 / Revised: 23 December 1996     

Evolutionary relationship between human major histocompatibility complexHLA-DR haplotypes

 HLA-DR haplotypes of the human major histocompatibility complex are organized in five different groups. They can be identified based on the serological specificity expressed by the polymorphic DRB1 locus and by the presence of a characteristic set of DRB genes. The nucleotide sequences of introns 4 and 5 of the two DRB genes (DRB1 ^* 01 and DRB6 ^* 01) from a DR1 haplotype and the three DRB genes (DRB1 ^* 15, DRB6 ^* 15, and DRB5 ^* 15), from a DR51 haplotype were determined. This study identified endogenous retroviral long terminal repeat elements (ERV9 LTR) located at identical positions in intron 5 of the DRB1 genes in both the DR1 and DR51 haplotypes. Phylogenetic analyses revealed a close evolutionary relationship between these two haplotypes. The DRB5 gene, unique for the DR51 haplotype, may have been lost by a recent gene deletion event creating the DR1 haplotype. A model for the evolution of the human DR haplotypes involving separate duplication and contraction events is presented. Received: 10 October 1995 / Revised: 22 November 1995     

Carbonic anhydrase II in new world monkeys

Carbonic anhydrase II electrophoretic patterns were investigated in 3113 animals belonging to 12 genera and 24 species of New World primates. Polymorphism was detected in 13 species. A total of 24 different alleles was postulated to explain the variability found; the genusAotus showed the highest (eight) number of such alleles. Three genera of the family Callitrichidae (Callithrix, Saguinus, andCebuella) presented five alleles that were not found among the Cebidae. Important markers at the generic level were observed inCallicebus (CA2 ^*6 andCA2 ^*12),Cebus (CA2 ^*10, CA2^*16, andCA2 ^*21), andAotus (CA2^*3, CA2^*4, CA2^*5, CA2^*9, CA2^*15, CA2^*17, CA2^*22, CA2^*23). CA2^*13 seems to be the most common allele among the Cebidae; six genera of this family showed frequencies higher than 70% of it.     

Analysis of the heterochromatin of <Emphasis Type="Italic">Cebus</Emphasis> (Primates,Platyrrhini) by micro-FISH and banding pattern comparisons

The karyotype of the neotropical primate genus Cebus (Platyrrhini: Cebidae), considered the most ancestral one, shows the greatest amount of heterochromatin described among Platyrrhini genera. Banding techniques and restriction enzyme digestion have previously revealed great variability of quantity and composition of heterochromatin in this genus. In this context, we use fluorescence in situ hybridization (FISH) to analyse this genomic region and discuss its possible role in the diversification of Cebus. We used a heterochromatin probe for chromosome 11 of Cebus libidinosus (11qHe+ CLI probe), obtained by chromosome microdissection. Twenty-six specimens belonging to the families Atelidae, Cebidae, Callitrichidae and Pithecidae (Platyrrhini) were studied. Fourteen out of 26 specimens were Cebus (Cebidae) individuals of C. libidinosus, C. xanthosternos, C. apella, C. nigritus, C. albifrons, C. kaapori and C. olivaceus. In Cebus specimens, we found 6 to 22 positive signals located in interstitial and telomeric positions along the different species. No hybridization signal was observed among the remaining Ceboidea species, thus reinforcing the idea of a Cebus-specific heterochromatin composed of a complex system of repetitive sequences.     

Molecular cytotaxonomy of New World monkeys (Platyrrhini) - comparative analysis of five species by multi-color chromosome painting gives evidence for a classification of Callimico goeldii within the family of Callitrichidae

Chromosome rearrangements are considered as "rare genomic changes" and can provide useful markers and even landmarks for reconstructing phylogenies complementary to DNA sequence data and bio-morphological comparisons. Here, we applied multi-directional chromosome painting to reconstruct the chromosome phylogeny and evolutionary relationships among the New World monkey (Platyrrhini) species Callithrix argentata, Cebuella pygmaea, Saguinus oedipus, Callithrix jacchus and Callimico goeldii. The results clarified several aspects of New Wold monkey phylogeny. In particular the phylogenetic position of C. goeldii was elucidated, which has been controversially discussed and variously classified in the family Callitrichidae, in the family Cebidae or in its own family Callimiconidae. Comparative genome maps were established by multi-color fluorescence in situ hybridization (FISH) with human, S. oedipus and Lagothrix lagothricha chromosome- specific DNA probes. From these data we reconstructed the putative ancestral karyotype of all Callitrichidae. Various derived chromosomal syntenies are shared by all five species and cytogenetically define Callitrichidae - including Callimico goeldii -- as a distinctive group within the Platyrrhini. C. pygmaea and C. argentata share identical chromosomal syntenies from which S. oedipus and C. jacchus differ by single independent translocations. A common derived chromosomal change links Callimico with the marmosets to the exclusion of the tamarins, however, it has further diverged from an ancestral marmoset karyotype by at least four apomorphic rearrangements. Saimiri sciureus, representing the Cebinae, exclusively shares a derived syntenic association with all Callithrichidae, defining the genus Saimiri as a sister group.     

Owl monkey MHC-DRB exon 2 reveals high similarity with several HLA-DRB lineages

One hundred and ten novel MHC-DRB gene exon 2 nucleotide sequences were sequenced in 96 monkeys from three owl monkey species (67 from Aotus nancymaae, 30 from Aotus nigriceps and 13 from Aotus vociferans). Owl monkeys, like humans, have high MHC-DRB allele polymorphism, revealing a striking similarity with several human allele lineages in the peptide binding region and presenting major convergence with DRB lineages from several Catarrhini (humans, apes and Old World monkeys) rather than with others New World monkeys (Platyrrhini). The parallelism between human and Aotus MHC-DRB reveals additional similarities regarding variability pattern, selection pressure and physicochemical constraints in amino acid replacements. These observations concerning previous findings of similarity between the Aotus immune system molecules and their human counterparts affirm this specie’s usefulness as an excellent animal model in biomedical research.Experiments carried out in this work complied with current Colombian Ministry of Health law and regulations governing animal care and handling.An erratum to this article can be found at     

The myoglobin of primates: the Night Monkey, Aotes trivirgatus (Cebidae,Platyrrhini, Anthropoidea)

The amino acid sequence of the myoglobin of the South American Night Monkey, Aotes trivirgatus, is identical to that of the marmoset (Callithrix jacchus [1]) except for residue 21 which is isoleucine in the marmoset, like in all other anthropoids, but valine in Aotes. Analysis of a possible pathway of the evolution of Aotes myoglobin using 18 known primate myoglobin sequences [2–5] supports the classification of the Night Monkey within Anthropoidea and Platyrrhini but it indicates that this species might be more closely related to the marmoset (family Callitrichidae) than to the family Cebidae as a member of which it is commonly classified.     

A Reexamination of the Phylogenetic Position of Callimico (Primates) Incorporating New Mitochondrial DNA Sequence Data

The New World monkeys are divided into two main groups, Callitrichidae and Cebidae. Callimico goeldii shares traits with both the Cebidae and the Callitrichidae. Recent morphological phyletic studies generally place Callimico as the most basal member of the Callitrichidae. In contrast, genetic studies (immunological, restriction fragment, and sequence data) have consistently placed Callimico somewhere within the Callitrichidae, not basal to this clade. A DNA sequence data set from the terminal 236 codons of the mitochondrial ND4 gene and the tRNA^His, tRNA^Ser, and tRNA^Leu genes was generated to clarify the position of Callimico. The sequences of 887 base pairs were analyzed by maximum-parsimony, neighbor-joining, and maximum-likelihood methods. The results of these various methods are generally congruent and place Callimico within the Callitrichidae between the marmosets (Callithrix and Cebuella) and the tamarins (Saguinus and Leontopithecus). Combined analyses of all suitable nuclear and mitochondrial gene sequences confirm the position of Callimico between the marmosets and the tamarins. As available molecular evidence indicates that Callimico is more closely related to the marmosets than to the tamarins, a reconsideration of the morphological evidence in light of the consensus tree from DNA sequence analyses is warranted. The marmosets and tamarins share four morphological characters (loss of the third molar, loss of the hypocone, reduced body size, reproductive twinning). Dwarfism may have evolved repeatedly among the Callitrichidae. It is well-known that the loss of a character can occur many times independently. The reproduction of marmosets and tamarins is extremely specialized and it is difficult to imagine that this complex and unique twinning system evolved separately in marmosets and tamarins. However, it is possible that a secondary reversal to single offspring took place in Callimico. Received: 20 March 1997 / Accepted: 17 December 1997     

Platyrrhine juvenile mortality in captivity and in the wild

I reviewed literature on juvenile mortality in the Platyrrhini in order to evaluate reproductive success in captive breeding. Juvenile mortality includes abortion, premature mortality, stillbirth and death of the unweaned young. The highest losses occur in the Callitrichidae (31% through 3 months of age; 86% through 6 months of age) and in Lagothrixspp. (around 50% through 1 month of age) among the Cebidae. High abortion rates occur in Saguinusand Aotus.High stillbirth incidences are reported for the Callitrichidae (Callithrixand Saguinus)and for the Cebidae (Saimiriand Aotus).Although most mortality occurs in the first week for most species, a considerable proportion of deaths occurs in the period from week 1 until weaning. Important causes of death are trauma and aberrant parental behavior. Prematurity plays an important role in perinatal death among the Callitrichidae. Dystocia is a major cause of stillbirth in Saimiri. Congenital malformations occur in Callithrix, Saguinus, Leontopithecus,and Saimiri.Infectious diseases play a secondary role in mortality, particularly during the first period of life. A higher mortality risk is present if the infant is male, if the litter size is different from two (Callitrichidae), if the mother is primiparous, captive born, or inexperienced, or if the group is small (Callitrichidae) or unstable (Cebidae).     

The evolutionary origin of the HLA-DR3 haplotype

The human HLA-DR3 haplotype consists of two functional genes (DRB1*03 and DRB3*01) and one pseudogene (DRB2), arranged in the order DRB1... DRB2... DRB3 on the chromosome. To shed light on the origin of the haplotype, we sequenced 1480 nucleotides of the HLA-DRB2 gene and aong stretches of two other genes, Gogo-DRB2 from a gorilla, Sylvia and Patr-DRB2 from a chimpanzee, Hugo. All three sequences (HLA-DRB2, Gogo-DRB2, Patr-DRB2) are pseudogenes. The HLA-DRB2 and Gogo-DRB2 pseudogenes lack exon 2 and contain a twenty-nucleotide deletion in exon 3, which destroys the correct translational reading frame and obliterates the highly conserved cysteine residue at position 173. The Patr-DRB2 pseudogene lacks exons 1 and 2; it does not contain the twenty-nucleotide deletion, but does contain a characteristic duplication of that part of exon 6 which codes for the last four amino acid residues of the cytoplasmic region. When the nucleotide sequences of these three genes are compared to those of all other known DRB genes, the HLA-DRB2 is seen as most closely related to Gogo-DRB2, indicating orthologous relationship between the two sequences. The Patr-DRB2 gene is more distantly related to these two DRB2 genes and whether it is orthologous to them is uncertain. The three genes are in turn most closely related to HLA-DRBVI (the pseudogene of the DR2 haplotype) and Patr-DRB6 (another pseudogene of the Hugo haplotype), followed by HLA-DRB4 (the functional but nonpolymorphic gene of the DR4 haplotype). These relationships suggest that these six genes evolved from a common ancestor which existed before the separation of the human, gorilla, and chimpanzee lineages. The DRB2 and DRB6 have apparently been pseudogenes for at least six million years (myr). In the human and the gorilla haplotype, the DRB2 pseudogene is flanked on each side by what appear to be related genes. Apparently, the DR3 haplotype has existed in its present form for more than six myr.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M86691–94.