Complete mtDNA genomes of Anopheles darlingi and an approach to anopheline divergence time

Abstract Background The complete sequences of the mitochondrial genomes (mtDNA) of members of the northern and southern genotypes of Anopheles (Nyssorhynchus) darlingi were used for comparative studies to estimate the time to the most recent common ancestor for modern anophelines, to evaluate differentiation within this taxon, and to seek evidence of incipient speciation. Methods The mtDNAs were sequenced from mosquitoes from Belize and Brazil and comparative analyses of structure and base composition, among others, were performed. A maximum likelihood approach linked with phylogenetic information was employed to detect evidence of selection and a Bayesian approach was used to date the split between the subgenus Nyssorhynchus and other Anopheles subgenera. Results The comparison of mtDNA sequences within the Anopheles darlingi taxon does not provide sufficient resolution to establish different units of speciation within the species. In addition, no evidence of positive selection in any protein-coding gene of the mtDNA was detected, and purifying selection likely is the basis for this lack of diversity. Bayesian analysis supports the conclusion that the most recent ancestor of Nyssorhynchus and Anopheles+Cellia was extant ~94 million years ago. Conclusion Analyses of mtDNA genomes of Anopheles darlingi do not provide support for speciation in the taxon. The dates estimated for divergence among the anopheline groups tested is in agreement with the geological split of western Gondwana (95 mya), and provides additional support for explaining the absence of Cellia in the New World, and Nyssorhynchus in the Afro-Eurasian continents

Scorpion venom stimulates biliary/duodenal motility and pancreatic exocrine secretion

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Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence

Common SNPs in nicotinic acetylcholine receptor genes (CHRN genes) have been associated with drug behaviors and personality traits, but the influence of rare genetic variants is not well characterized. The goal of this project was to identify novel rare variants in CHRN genes in the Center for Antisocial Drug Dependence (CADD) and Genetics of Antisocial Drug Dependence (GADD) samples and to determine if low frequency variants are associated with antisocial drug dependence. Two samples of 114 and 200 individuals were selected using a case/control design including the tails of the phenotypic distribution of antisocial drug dependence. The capture, sequencing, and analysis of all variants in 16 CHRN genes (CHRNA1-7, 9, 10, CHRNB1-4, CHRND, CHRNG, CHRNE) were performed independently for each subject in each sample. Sequencing reads were aligned to the human reference sequence using BWA prior to variant calling with the Genome Analysis ToolKit (GATK). Low frequency variants (minor allele frequency < 0.05) were analyzed using SKAT-O and C-alpha to examine the distribution of rare variants among cases and controls. In our larger sample, the region containing the CHRNA6/CHRNB3 gene cluster was significantly associated with disease status using both SKAT-O and C-alpha (unadjusted p values < 0.05). More low frequency variants in the CHRNA6/CHRNB3 gene region were observed in cases compared to controls. These data support a role for genetic variants in CHRN genes and antisocial drug behaviors

Mitochondrial DNA sequences of primates: Tempo and mode of evolution

We cloned and sequenced a segment of mitochondrial DNA from human, chimpanzee, gorilla, orangutan, and gibbon. This segment is 896 bp in length, contains the genes for three transfer RNAs and parts of two proteins, and is homologous in all 5 primates. The 5 sequences differ from one another by base substitutions at 283 positions and by a deletion of one base pair. The sequence differences range from 9 to 19% among species, in agreement with estimates from cleavage map comparisons, thus confirming that the rate of mtDNA evolution in primates is 5 to 10 times higher than in nuclear DNA. The most striking new finding to emerge from these comparisons is that transitions greatly outnumber transversions. Ninety-two percent of the differences among the most closely related species (human, chimpanzee, and gorilla) are transitions. For pairs of species with longer divergence times, the observed percentage of transitions falls until, in the case of comparisons between primates and non-primates, it reaches a value of 45. The time dependence is probably due to obliteration of the record of transitions by multiple substitutions at the same nucleotide site. This finding illustrates the importance of choosing closely related species for analysis of the evolutionary process. The remarkable bias toward transitions in mtDNA evolution necessitates the revision of equations that correct for multiple substitutions at the same site. With revised equations, we calculated the incidence of silent and replacement substitutions in the two protein-coding genes. The silent substitution rate is 4 to 6 times higher than the replacement rate, indicating strong functional constraints at replacement sites. Moreover, the silent rate for these two genes is about 10% per million years, a value 10 times higher than the silent rate for the nuclear genes studied so far. In addition, the mean substitution rate in the three mitochondrial tRNA genes is at least 100 times higher than in nuclear tRNA genes. Finally, genealogical analysis of the sequence differences supports the view that the human lineage branched off only slightly before the gorilla and chimpanzee lineages diverged and strengthens the hypothesis that humans are more related to gorillas and chimpanzees than is the orangutan.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48036/1/239_2005_Article_BF01734101.pd