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Biomedical subjects

W E Mayer

Publications and source records attributed to W E Mayer.

51 records · Page 3Linked to original sources

Trans-species origin of Mhc-DRB polymorphism in the chimpanzee.

Trans-specific evolution of allelic polymorphism at the major histocompatibility complex loci has been demonstrated in a number of species. Estimating the substitution rates and the age of trans-specifically evolving alleles requires detailed information about the alleles in related species. We provide such information for the chimpanzee DRB genes. DNA fragments encompassing exon 2 were amplified in vitro from genomic DNA of ten chimpanzees. The nucleotide sequences were determined and their relationship to the human DRB alleles was evaluated. The alleles were classified according to their position in dendrograms and the presence of lineage-specific motifs. Twenty alleles were found at the expressed loci Patr-DRB1, -DRB3, -DRB4, -DRB5, and at the pseudogenes Patr-DRB6, -DRB7; of these, 13 are new alleles. Two other chimpanzee sequences were classified as members of a new lineage tentatively designated DRBX. Chimpanzee counterparts of HLA-DRB1*01 and *04 were not detected. The number of alleles found at individual loci indicates asymmetrical distribution of polymorphism between humans and chimpanzees. Estimations of intra-lineage divergence times suggest that the lineages are more than 30 million years old. Predictions of major chimpanzee DRB haplotypes are made.

Amino Acid Sequence↗

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↗

Major-histocompatibility-complex DRB genes of a New-World monkey, the cottontop tamarin (Saguinus oedipus).

The DRB region of the human and great-ape major histocompatibility complex displays not only gene but also haplotype polymorphism. The number of genes in the human DRB region can vary from one to four, and even greater variability exists among the DRB haplotypes of chimpanzees, gorillas, and orangutans. Accumulating evidence indicates that, like gene polymorphism, part of the haplotype polymorphism predates speciation. In an effort to determine when the gene haplotype polymorphisms emerged in the primate lineage, we sequenced three cDNA clones of the New-World monkey, the cottontop tamarin (Saguinus oedipus). We could identify two DRB loci in this species, one (Saoe-DRB1) occupied by apparently functional alleles (*0101 and *0102) which differ by only two nucleotide substitutions and the other (Saoe-DRB2) occupied by an apparent pseudogene. The Saoe-DRB2 gene contains an extra sequence derived from the 3' portion of exon 2 and placed 5' to this exon. This sequence contains a stop codon which makes the translation of the bulk of the Saoe-DRB2 gene unlikely. Preliminary Southern blot hybridization analysis with probes derived from these two genes suggests that both the DRB gene polymorphism and the haplotype polymorphism in the cottontop tamarin may be low. In most individuals the DRB region of this species probably consists of three genes. Comparisons of the Saoe-DRB sequences with those of other primates suggest that probably all of the DRB genes found until now in the Catarrhini were derived from a common ancestor after the separation of the Catarrhini and Platyrrhini lineages. The extant DRB gene and haplotype polymorphism may therefore have been founded in the mid-Oligocene some 33 Mya.

Amino Acid Sequence↗

Effects of tetraethylammoniumchloride (TEA), vanadate, and alkali ions on the lateral leaflet movement rhythm of Desmodium motorium (Houtt.) Merr.

The period (approximately 3-5 min) of the ultradian rhythm of the lateral leaflet movement of Desmodium motorium is strongly lengthened (less than or equal to 30-40%) by the K+ channel blocker tetraethylammoniumchloride (20, 30, and 40 mM) and vanadate (0.5 and 1 mM), which is an effective inhibitor of the plasma membrane-bound H+ pump. The alkali ions K+, Na+, Rb+, and Cs+ (10-40 mM) shorten the period only slightly (less than or equal to 10-15%). Li+ (5-30 mM), however, increases the period of the leaflet rhythm drastically (less than or equal to 80%). We concluded that the plasmalemma-H(+)-ATPase-driven K+ transport through K+ channels is an essential component of the ultradian oscillator of Desmodium, as has been proposed for the circadian oscillator.

Activity Cycles↗

Shared class II MHC polymorphisms between humans and chimpanzees.

To gain an insight into the evolution of the major histocompatibility complex alleles, three DRB and one DRA genes were isolated from chimpanzee cDNA libraries. The nucleotide sequences of the chimpanzee DRB (ChLA-DRB) genes were then compared with those of the available HLA-DRB alleles by constructing unrooted phylogenetic trees. All three ChLA-DRB genes were found to be more closely related to certain HLA-DRB alleles than unrelated HLA-DRB alleles are to each other. Since available evidence does not support the convergent evolution of MHC alleles, this result is consistent with the idea that closely related ChLA-DRB and HLA-DRB alleles are derived from common ancestral alleles, the existence of which predates the divergence of human and chimpanzee lineages. The predicted amino acid sequences of mature ChLA-DRA and HLA-DRA molecules differ by only one amino acid.

Amino Acid Sequence↗

Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans-species mode of evolution.

To obtain an insight into the evolutionary origin of the major histocompatibility complex (MHC) class I polymorphism, a cDNA library was prepared from a heterozygous chimpanzee cell line expressing MHC class I molecules crossreacting with allele-specific HLA-A11 antibodies. The library was screened with human class I locus-specific DNA probes, and clones encoding both alleles at the A and B loci have been identified and sequenced. In addition, the sequences of two HLA-A11 subtypes differing by a single nucleotide substitution have been obtained. The comparison of chimpanzee and human sequences revealed a close similarity (up to 98.5%). The chimpanzee A locus alleles showed greatest similarity to the human HLA-A11/A3 family of alleles, one of them being very close to HLA-A11. Similarly, segments of the ChLA-B alleles displayed greatest similarity to certain HLA-B alleles. The calculated evolutionary branch point for the A11-like alleles is 7 x 10(6) to 9 x 10(6) years, whereas the other A locus alleles diverged between 12 x 10(6) and 17 x 10(6) years ago. Since the human and chimpanzee lineages separated 5 x 10(6) to 7 x 10(6) years ago, our data support the notion that during evolution, MHC alleles are transmitted from one species to the next.

Alleles↗

Osmotica, dimethyl sulfoxide, parahydroxymercuribenzoate, and cyanide change the period of the circadian clock in the pulvini of Phaseolus coccineus L.

Several substances change the period length of the circadian oscillator in the laminar pulvinus of Phaseolus coccineus L. if offered continuously via the transpiration stream to the isolated leaves in continuous light and constant temperature. The osmotica mannitol and PEG 6000 (polyethylene glycol) lengthen the circadian period from 27.9 hr (control) to about 29.5 hr. The dose-response of both substances reveal saturation curves. DMSO (dimethyl sulfoxide) lengthens the circadian period much more strongly than the osmotica. The dose-response curve reflects a curvilinear dependence of the period length from the DMSO concentration. PHMB (p-hydroxymercuribenzoate) and NaCN shorten the circadian period. The dose-response curve for PHMB is a saturation curve; saturation is reached at 80 microM PHMB with a period length of about 25.7 hr. We conclude from these results that the period of the circadian oscillator in the Phaseolus pulvinus is not directly homeostatically regulated but influenced by the intracellular milieu which can be changed by affecting membrane permeability, active transport systems or other regulatory systems within the cells.

Biological Clocks↗

Structure of the murine Ia-associated invariant (Ii) chain as deduced from a cDNA clone.

The invariant (Ii) chain is a membrane-spanning glycoprotein found intracellularly associated with class II major histocompatibility complex (MHC) molecules. Using hybrid-selected translation and the Ii-specific monoclonal antibody In-1, we have isolated a cDNA clone (pIi-5) coding for most of the Ii chain. Sequence analysis of this clone reveals an open reading frame encoding 169 amino acid residues. The protein is rich in methionine and contains two potential N-glycosylation sites. No stretch of uncharged amino acid residues, characteristic for a membrane-spanning segment, is found close to the COOH-terminal end. There is one, however, close to the NH2-terminal end. As it is know that approximately 20 amino acid residues of Ii chain are exposed on the cytoplasmic side, we conclude that the Ii chain spans the membrane exposing the NH2 terminus on the cytoplasmic side and the COOH terminus on the luminal side.

Amino Acid Sequence↗

Electrical Membrane Properties and Circadian Rhythm in Extensor Cells of the Laminar Pulvini of Phaseolus coccineus L.

Circadian changes of three parameters of electrical properties in extensor cells of the laminar pulvini of Phaseolus coccineus L. have been recorded by standard microelectrode techniques. In the low turgor state of the cells, the resting potential and the CN(-) (1 millimolar NaCN) induced depolarizations are large, while the K(+)-induced voltage changes are small, and vice versa in the high turgor state. These results demonstrate that during a circadian cycle the low turgor state of the extensor cells is correlated with the active state of an electrogenic pump. This correlation can be explained by electroosmosis.

Journal Article↗

Molecular phylogeny of Philippine freshwater sardines based on mitochondrial DNA analysis.

The commercially important Sardinella species (family Clupeidae or herrings) usually thrive in marine environments. An exception is Sardinella tawilis of Taal Lake, Batangas, Philippines, the only known freshwater sardine. This species is believed to have immigrated from Balayan Bay to the lake when it was formed in the course of volcanic eruptions some 240 years ago. To determine the relationship of S. tawilis to the marine species S. albella, S. fimbriata, and S. longiceps from the Balayan Bay we sequenced 358 bp of the cytochrome b gene and the mitochondrial control region. The cytochrome b gene was highly conserved and contained little phylogenetic information. The control region sequences, however, demonstrated two highly diversified main haplotypes grouping S. tawilis with S. albella, as shown by maximum parsimony and neighbor-joining analysis. The haplotypes are characterized by the presence of an 81 bp indel and up to eight 35 bp tandem repeat elements. The repeat copy number varied within individuals of S. tawilis and S. albella, thus showing heteroplasmy in these two species only. The analysis of two subpopulations of S. tawilis revealed restricted substitutions that may indicate the beginning of genetic differentiation of the two subpopulations.

Animals↗

Fish trypanosomes: their position in kinetoplastid phylogeny and variability as determined from 12S rRNA kinetoplast sequences.

Fish trypanosomes have traditionally been classified according to the host species from which they were isolated, each isolate being regarded as a distinct species. To test the soundness of this practice, the genetic variabilities of the kinetoplast 12S rRNA-encoding genes of different fish trypanosomes isolates were compared. The DNAs were extracted from trypanosomes cloned from blood samples of 15 donors representing ten different fish species in four orders from waters of three major river systems of Central and Northern Europe. Comparison with other trypanosomatid sequences revealed that the fish trypanosomes form a monophyletic group with Trypanosoma brucei as a sister group. Pairwise comparisons of genetic distances yielded a wide range of continuous variation with no indication of any discontinuities attributable to barriers to gene flow. The genetic distances did not correlate with either the identity of the host species or geography. The host specificity of fish trypanosomes appears to be limited.

Animals↗