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H Kupfermann

Publications and source records attributed to H Kupfermann.

6 recordsLinked to original sources
PubMed1999

Evolution of Mhc-DRB introns: implications for the origin of primates.

Introns are generally believed to evolve too rapidly and too erratically to be of much use in phylogenetic reconstructions. Few phylogenetically informative intron sequences are available, however, to ascertain the validity of this supposition. In the present study the supposition was tested on the example of the mammalian class II major histocompatibility complex (Mhc) genes of the DRB family. Since the Mhc genes evolve under balancing selection and are believed to recombine or rearrange frequently, the evolution of their introns could be expected to be particularly rapid and subject to scrambling. Sequences of intron 4 and 5 DRB genes were obtained from polymerase chain reaction-amplified fragments of genomic DNA from representatives of six eutherian orders-Primates, Scandentia, Chiroptera, Dermoptera, Lagomorpha, and Insectivora. Although short stretches of the introns have indeed proved to be unalignable, the bulk of the intron sequences from all six orders, spanning >85 million years (my) of evolution, could be aligned and used in a study of the tempo and mode of intron evolution. The analysis has revealed the Mhc introns to evolve at a rate similar to that of other genes and of synonymous sites of non-Mhc genes. No evidence of homogenization or large-scale scrambling of the intron sequences could be found. The Mhc introns apparently evolve largely by point mutations and insertions/deletions. The phylogenetic signals contained in the intron sequences could be used to identify Scandentia as the sister group of Primates, to support the existence of the Archonta superorder, and to confirm the monophyly of the Chiroptera.

Animals↗
PubMed1999

Molecular clock and recombination in primate Mhc genes.

To set an accurate chronological framework to the evolution of primate class I and II genes in the major histocompatibility complex (Mhc), the rate of silent nucleotide substitutions in exons and introns is examined for various cDNA and genome sequences currently available. The rate is sensitive to the GC content and correlates negatively with increased GC biases at the third codon positions of Mhc genes. The intergenic recombination rate in the HLA region is estimated from the synonymous nucleotide differences at 37 linked loci. Any HLA subregion is recombined more or less at the ordinary rate of 1 cM per 1 Mb, although the rate may be reduced in some subregions. This information is used to discuss HLA haplotypes when they are applied to studies of human demography. The unusual polymorphism in the alpha-helix of HLA-DRB1 is also revisited in relation to intragenic recombination, but the molecular mechanism and the evolutionary cause both remain enigmatic.

Animals↗
PubMed1996

Bovine viral diarrhea virus: characterization of a cytopathogenic defective interfering particle with two internal deletions.

Molecular characterization of bovine viral diarrhea virus pair 13 revealed that isolate CP13 is composed of a cytopathogenic (cp) defective interfering particle (DI13) and a noncytopathogenic (noncp) helper virus. The DI13 genome possesses two internal deletions of 1,611 and 3,102 nucleotides. Except for a small fragment of the gene coding for glycoprotein E1, all structural protein genes are deleted together with most of the Npro gene, the region coding for nonstructural proteins p7 and NS2. While the amino terminus of NS3 seems to be strictly conserved for all other cp bovine viral diarrhea viruses, NS3 of DI13 is amino-terminally truncated and fused to 23 amino acids derived from Npro and E1. Characterization of the DI-helper virus system revealed a striking discrepancy between RNA production and generation of infectious viruses.

Animals↗
PubMed1993

Mhc-DRB genes of platyrrhine primates.

The two infraorders of anthropoid primates, Platyrrhini (New World monkeys) and Catarrhini (Old World monkeys and the hominoids) are estimated to have diverged from a common ancestor 37 million years ago. The major histocompatibility complex class II DRB gene and haplotype polymorphism of the Catarrhini has been characterized in several recent studies. The present study was undertaken to obtain information on the DRB polymorphism of the Platyrrhini. Fifty-five complete exon 2 DRB sequences were obtained from six species of Platyrrhini representing both the Callitrichidae and the Cebidae families. Combined with the results of a parallel contig mapping study, our data indicate that at least three loci (DRB1*03, DRB3, and DRB5) are shared by the Catarrhini and the Platyrrhini. However, the three loci are occupied by functional genes in the former infraorder and mostly by pseudogenes in the latter. Instead of the pseudogenes, the Platyrrhini have evolved a new set of apparently functional genes-DRB11 and DRB*W12 through DRB*W19, which have thus far not been found in the Catarrhini. The DRB*W13, *W14, *W15, *W17, *W18, and *W19 genes seem to be restricted to the Cebidae family, whereas the DRB*W16 locus has so far been documented in the Callitrichidae family only. The DRB alleles of the cotton-top tamarin, and perhaps also those of the common marmoset (both members of the family Callitrichidae), are characterized by low nucleotide diversity, possibly indicating that they diverged from a common ancestral gene relatively recently.

Amino Acid Sequence↗
PubMed1992

Shared polymorphism between gorilla and human major histocompatibility complex DRB loci.

A high degree of polymorphism and high nucleotide diversity mark the functional genes of the major histocompatibility complex (Mbc). Alleles at the different Mbc loci can be classified into distinct lineages that are shared between species and, therefore, are presumed to have been founded before speciation. We have sequenced the most polymorphic part of 25 gorilla Mbc-DRB genes from six individuals. (The DRB genes code for the beta-polypeptide chain of the alpha beta heterodimer that constitutes one family of the class II MHC molecules.) Fifteen of the sequences identify new alleles at four DRB loci; each of the six gorillas was heterozygous at one of the loci at least. Thirteen of the alleles could be assigned to lineages identified previously; the remaining two alleles represent new lineages. All the major human DRB allelic lineages are now known to be shared with apes, and all must have originated before the human-gorilla-chimpanzee divergence more than six million years (my) ago. The presence of some of the gorilla and human lineages in Old World monkeys suggests that these lineages emerged before the divergence of apes and cercopithecids. We argue that the major allelic lineages at the DRB1 locus began to diverge shortly after the rounds of duplication that generated the different DRB loci now found in the hominoids and that this event occurred more than 30 my ago. Comparison of closely related gorilla DRB sequences indicates that polymorphism may be generated by several mechanisms: point mutations, slippage during DNA replication, and recombination. Deduced gene linkages provide evidence for transspecies evolution of haplotype polymorphism.

Alleles↗