ABSTRACT
We report the nucleotide sequences of turkey (Meleagris gallopavo) major histocompatibility complex (MHC) class II loci (beta 1 domain or exon 2 encoding the peptide-binding region). In the present investigation, three distinct sequences from the beta 1 domain of turkey MHC class II were isolated. A BLAST search and phylogenetic analysis revealed that turkey MHC sequences are most similar to chicken and peacock MHC. There was no strong evidence of recombination among the turkey MHC sequences or with other avian MHC, but diversity was high. The diversity in this peptide-binding region may be the result of point mutation and balancing selection or frequent gene conversion within turkey. However, more work and data are needed to understand the evolution of turkey and other avian MHC. Moreover, polymerase chain reaction-restriction fragment-length polymorphism analysis of exon 2 using the Hinf I restriction enzyme demonstrated three restriction patterns and a preliminary evidence of multiple beta loci in turkey. PCR-RFLP analysis of turkey MHC class II loci could be a promising method of MHC genotyping, when more sequences are available. Turkey MHC haplotypes identified earlier by RFLP analysis should be sequenced to standardize turkey MHC nomenclature and to develop DNA based method of haplotyping.
Subject(s)
Chickens/immunology , Histocompatibility Antigens Class II/classification , Histocompatibility Antigens Class II/genetics , Turkeys/immunology , Amino Acid Sequence , Animals , Base Sequence , Chickens/genetics , Cloning, Molecular , Exons/genetics , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Protein Structure, Tertiary/genetics , Sequence Alignment , Turkeys/geneticsABSTRACT
The molecular evolution of DAX1, SRY, and SOX9, genes involved in mammalian sex determination, was examined in six primate species. DAX1 and SRY have been added to the X and Y chromosomes, respectively, during mammalian evolution, whereas SOX9 remains autosomal. We determined the genomic sequences of DAX1, SRY, and SOX9 in all six species, and calculated K(a), the number of nonsynonymous substitutions per nonsynonymous site, and compared this with the K(s), the number of synonymous substitutions per synonymous site. Phylogenetic trees were constructed by means of the DAX1, SRY, and SOX9 coding sequences, and phylogenetic analysis was performed using maximum likelihood. Overall measures of gene and protein similarity were closer for DAX1 and SOX9, but DAX1 exhibited nonsynonymous amino acid substitutions at an accelerated frequency relative to synonymous changes, similar to SRY and significantly higher than SOX9. We conclude that, at the protein level, DAX1 and SRY are under less selective pressure to remain conserved than SOX9, and, therefore, diverge more across species than does SOX9. These results are consistent with evolutionary stratification of the mammalian sex determination pathway, analogous to that for sex chromosomes.
Subject(s)
DNA-Binding Proteins/genetics , Evolution, Molecular , High Mobility Group Proteins/genetics , Nuclear Proteins , Phylogeny , Primates/genetics , Receptors, Retinoic Acid/genetics , Repressor Proteins , Sex Determination Processes , Transcription Factors/genetics , Amino Acid Sequence , Amino Acid Substitution/genetics , Animals , Conserved Sequence/genetics , DAX-1 Orphan Nuclear Receptor , DNA-Binding Proteins/chemistry , Genetic Variation/genetics , High Mobility Group Proteins/chemistry , Humans , Likelihood Functions , Molecular Sequence Data , Mutagenesis/genetics , Primates/classification , Receptors, Retinoic Acid/chemistry , SOX9 Transcription Factor , Selection, Genetic , Sequence Alignment , Sex-Determining Region Y Protein , Transcription Factors/chemistryABSTRACT
We use a mathematical model to study the dynamics of HIV-1 replication during structured treatment interruptions (STIs) in infected patients. The model predicts rapid viral rebound, restoration of a latently infected cell pool, and critically, partially resistant mutant rebound that may be missed because of high levels of wild type virus. Because partially resistant viruses are capable of mutating to full resistance, a substantial increase in their numbers represents a threat to therapeutic response durability. Compared with continued treatment, STIs may increase the chance of mutation to full resistance by several thousandfold.
Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/drug therapy , HIV-1/drug effects , HIV-1/genetics , Mutation , Anti-HIV Agents/therapeutic use , Drug Administration Schedule , Drug Resistance, Microbial/genetics , Drug Therapy, Combination , HIV Infections/virology , Humans , Models, Biological , Risk Factors , Viral Load , Virus LatencyABSTRACT
BACKGROUND: Most of the studies of HIV-1 infection in South America have been limited to Brazil and little is known about the viral variants that are causing disease elsewhere in the continent. AIM: To determine the characteristics of the viral variants present in Chile as well as patterns of viral transmission. MATERIAL AND METHODS: Viral sequences were obtained from 21 HIV-1 infected people from Santiago, Chile who were infected either via sexual contact or intravenous drug use. Cloned sequences obtained from both the third variable and conserved regions of the envelope as well as the viral protease were evaluated. RESULTS: We found only clade B subtype viruses in Santiago. An evaluation of the envelope gene revealed no evidence that the sequences were monophyletic by risk group. A number of the protease sequences were predicted to encode amino acid substitutions commonly found during selection for protease inhibitor resistance. CONCLUSIONS: The HIV-1 strains studied in Chile, belong to the subtype B. There is no molecular evidence of separate introductions of the virus into the different risk groups. A number of substitutions in the protease gene that may confer resistance to protease inhibitors were found in patients with no previous exposure to this class of drugs.
