Reduced natural selection associated with low recombination in Drosophila melanogaster

Synonymous codons are not used equally in many organisms, and the extent of codon bias varies among loci. Earlier studies have suggested that more highly expressed loci in Drosophila melanogaster are more biased, consistent with findings from several prokaryotes and unicellular eukaryotes that codon bias is partly due to natural selection for translational efficiency. We link this model of varying selection intensity to the population-genetics prediction that the effectiveness of natural selection is decreased under reduced recombination. In analyses of 385 D. melanogaster loci, we find that codon bias is reduced in regions of low recombination (i.e., near centromeres and telomeres and on the fourth chromosome). The effect does not appear to be a linear function of recombination rate; rather, it seems limited to regions with the very lowest levels of recombination. The large majority of the genome apparently experiences recombination at a sufficiently high rate for effective natural selection against suboptimal codons. These findings support models of the Hill-Robertson effect and genetic hitchhiking and are largely consistent with multiple reports of low levels of DNA sequence variation in regions of low recombination.      

The Agnogene of the Human Polyomavirus BK Is Expressed

Primate polyomavirus genomes all contain an open reading frame at the 5′ end of the late coding region called the agnogene. A simian virus 40 agnoprotein with unknown functions has previously been demonstrated. We now show that a BK virus agnoprotein appears in the perinuclear area and cytoplasm late in the infectious cycle. It is phosphorylated in vivo and coimmunoprecipitates with a subset of host cell proteins.     

DNA Sequence Variation at the Period Locus Reveals the History of Species and Speciation Events in the Drosophila Virilis Group

The virilis phylad of the Drosophila virilis group consists of five closely related taxa: D. virilis, D. lummei, D. novamexicana, D. americana americana and D. americana texana. DNA sequences from a 2.1-kb pair portion of the period locus were generated in four to eight individuals from each of the five taxa. We found evidence of recombination and high levels of variation within species. We found no evidence of recent natural selection. Surprisingly there was no evidence of divergence between D. a. americana and D. a. texana, and they collectively appear to have had a large historical effective population size. The ranges of these two taxa overlap in a large hybrid zone that has been delineated in the eastern U.S. on the basis of the geographic pattern of a chromosomal fusion. Also surprisingly, D. novamexicana appears to consist of two distinct groups each with low population size and no gene flow between them.     

Homozygous and Hemizygous Viability Variation on the X Chromosome of DROSOPHILA MELANOGASTER

We report here a study of viability inbreeding depression associated with the X chromosome of Drosophila melanogaster. Fifty wild chromosomes from Mt. Sinai, New York, and 90 wild chromosomes from Death Valley, California, were extracted using the marked FM6 balancer chromosome and viabilities measured for homozygous and heterozygous females, and for hemizygous males, relative to FM6 males as a standard genotype. No statistically significant female genetic load was observed for either chromosome set, although a 95% confidence limit estimated the total load <0.046 for the samples pooled. About 10% of the Death Valley chromosomes appear to be "supervital" as homozygotes. There is little evidence for a pervasive sex-limited detrimental load on the X chromosome; the evidence indicates nearly identical viability effects in males and homozygous females excluding the supervital chromosomes. The average degree of dominance for viability polygenes is estimated between 0.23 to 0.36, which is consistent with autosomal variation and implies near additivity. We conclude that there is little genetic load associated with viability variation on the X chromosome and that the substantial reduction in total fitness observed for chromosome homozygosity in an earlier study may be due largely to sex-limited fertility in females.     

Divergence population genetics of chimpanzees

The divergence of two subspecies of common chimpanzees (Pan troglodytes troglodytes and P. t. verus) and the bonobo (P. paniscus) was studied using a recently developed method for analyzing population divergence. Under the isolation with migration model, the posterior probability distributions of divergence time, migration rates, and effective population sizes were estimated for large multilocus DNA sequence data sets drawn from the literature. The bonobo and the common chimpanzee are estimated to have diverged approximately 0.86 to 0.89 MYA, and the divergence of the two common chimpanzee subspecies is estimated to have occurred 0.42 MYA. P. t. troglodytes appears to have had a larger effective population size (22,400 to 27,900) compared with P. paniscus, P. t. verus, and the ancestral populations of these species. No evidence of gene flow was found in the comparisons involving P. paniscus; however a clear signal of unidirectional gene flow was found from P. t. verus to P. t. troglodytes (2Nm = 0.51).     

The insulin-like growth factor system and markers of inflammation in adult patients with inflammatory bowel disease

BACKGROUND AND OBJECTIVES: Catabolism and growth impairment are well-known complications of inflammatory bowel disease (IBD). Recent studies have demonstrated significant changes in the IGF system in IBD patients. The aim of the present study was to investigate correlations between the IGF system and markers of inflammation in IBD. METHODS: A cross-sectional study comprising 99 IBD patients (Crohn's disease (CD, n = 50) and ulcerative colitis (UC, n = 49)). Correlations between markers of inflammation and IGF-I, IGF-II and IGFBP-3 were examined in CD and UC patients in remission and relapse. The patients were clinically scored using Crohn's Disease Activity Index (CDAI) for CD patients and Activity Index (AI) for UC patients. RESULTS: In the UC group we found correlations between IGF-I and CRP (r(s) = Spearman's rho) (r(s) = -0.40, p < 0.01) and albumin (r(s) = 0.46, p < 0.001), IGFBP-3 and albumin (r(s) = 0.36, p < 0.01) and AI score (r(s) = -0.31, p < 0.05). IGF-II correlated with CRP (r(s) = -0.42, p < 0.01), IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), AI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). In the CD group we found correlations between IGF-I and CRP (r(s) = -0.40, p < 0.05), and albumin (r(s) = -0.46, p < 0.01), IGFBP-3 and albumin (r = 0.36, p < 0.01). IGF-II correlated with IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), CDAI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). CONCLUSIONS: IGF-I, IGF-II and IGFBP-3 are correlated to albumin and IGF-I and IGF-II are correlated to CRP in IBD patients. Further, IGF-II is correlated to IL-6 in IBD patients. This may suggest a correlation between inflammation and the IGF system with involvement in muscle and bone catabolism in IBD.     

Regional localization of a trophoblast antigen-related sequence and 16 other sequences to human chromosomes 6q using somatic cell hybrids.

Using a panel of 13 hybrid cell lines, we have regionally localized 22 markers to the long arm of chromosome 6. Revised or new locations are provided for 17 of the markers, and preliminary assignments to chromosome 6 of 11 loci are confirmed. The location of NT5, previously determined by antigen expression in hybrids, has been confirmed at 6q14-q15 by using a cDNA probe. Other DNA probes include one new anonymous sequence, designated D6S130, that maps to 6q12 and 4 VNTR probes that map to the proterminal band, 6q27. Probe CRI-L1065 also maps to 6q21, CRI-994 maps to 6q21-qter, and CRI-L322 maps to 6q14-15, information that may assist the merging of physical and genetic maps.     

Assignment of ecto-5′-nucleotidase to human chromosome 6

Summary Ecto-5-nucleotidase activity (5NT) was measured on whole cells of 26 human x Chinese hamster hybrids. Concordance analysis showed 100% correlation between enzyme activity and inheritance of human chromosome 6. This observation was confirmed by a segregation analysis in which cells of a hybrid containing chromosome 6 were stained by indirect immunofluorescence for HLA Class 1 antigen and sorted by a fluorescence-activated cell sorter (FACS). Cells in the HLA^- compartment were cloned and expression of HLA and 5NT was determined. Of nine clones, three were HLA^-, 5NT^- and six were HLA⁺, 5NT⁺, supporting the linkage of 5NT to chromosome 6.     

IMa2p – parallel MCMC and inference of ancient demography under the Isolation with migration (IM) model

IMa2 and related programs are used to study the divergence of closely related species and of populations within species. These methods are based on the sampling of genealogies using MCMC, and they can proceed quite slowly for larger data sets. We describe a parallel implementation, called IMa2p, that provides a nearly linear increase in genealogy sampling rate with the number of processors in use. IMa2p is written in OpenMPI and C++, and scales well for demographic analyses of a large number of loci and populations, which are difficult to study using the serial version of the program.