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- Morrow, E. H., et al.
(author)
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Assessing the extent of genome-wide intralocus sexual conflict via experimentally enforced gender-limited selection
- 2008
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In: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 21:4, s. 1046-1054
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Journal article (peer-reviewed)abstract
- Intralocus sexual conflict, which occurs when a trait is selected in opposite directions in the two sexes, is a taxonomically widespread phenomenon. The strongest genetic evidence for a gender load due to intralocus sexual conflict comes from the Drosophila melanogaster laboratory model system, in which a negative genetic correlation between male and female lifetime fitness has been observed. Here, using a D. melanogaster model system, we utilize a novel modification of the 'middle class neighbourhood' design to relax selection in one sex, while maintaining selection in the other. After 26 generations of asymmetrical selection, we observed the expected drop in fitness of the non-selected sex compared to that of the selected sex, consistent with previous studies of intralocus sexual conflict in this species. However, the fitness of the selected sex also dropped compared to the base population. The overall decline in fitness of both the selected and the unselected sex indicates that most new mutations are harmful to both sexes, causing recurrent mutation to build a positive genetic correlation for fitness between the sexes. However, the steeper decay in the fitness of the unselected sex indicates that a substantial number of mutations are gender-limited in expression or sexually antagonistic. Our experiment cannot definitively resolve these two possibilities, but we use recent genomic data and results from previous studies to argue that sexually antagonistic alleles are the more likely explanation.
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- Ram, Sanjay, et al.
(author)
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Heptose I glycan substitutions on Neisseria gonorrhoeae lipooligosaccharide influence C4b-binding protein binding and serum resistance.
- 2007
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In: Infection and Immunity. - 1098-5522. ; 75:8, s. 4071-4081
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Journal article (peer-reviewed)abstract
- Lipooligosaccharide (LOS) heptose (Hep) glycan substitutions influence gonococcal serum resistance. Several gonococcal strains bind the classical complement pathway inhibitor, C4b-binding protein (C4BP), via their porin (Por) molecule to escape complement-dependent killing by normal human serum (NHS). We show that the proximal glucose (Glc) on HepI is required for C4BP binding to Por1B-bearing gonococcal strains MS11 and 1291 but not to FA19 (Por1A). The presence of only the proximal Glc on HepI (lgtE mutant) permitted maximal C4BP binding to MS11 but not to 1291. Replacing 1291 lgtE Por with MS11 Por increased C4BP binding to levels that paralleled MS11 lgtE, suggesting that replacement of the Por1B molecule dictated the effects of HepI glycans on C4BP binding. The remainder of the strain background did not affect C4BP binding; replacing the Por of strain F62 with MS11 Por (F62 PorMS11) and truncating HepI mirrored the findings in the MS11 background. C4BP binding correlated with resistance to killing by NHS in most instances. F62 PorMS11 and its lgtE mutant were sensitive to NHS despite binding C4BP, secondary to kinetically overwhelming classical pathway activation and possibly increased alternative pathway activation (measured by factor Bb binding) by the F62 background. FA19 lgtF (HepI unsubstituted) resisted killing by only 10% NHS, not 50% NHS, despite binding levels of C4BP similar to those of FA19 and FA19 lgtE (both resistant to 50% serum), suggesting a role for the proximal Glc in serum resistance independently of C4BP binding. This study provides mechanistic insights into how HepI LOS substitutions affect the serum resistance of N. gonorrhoeae.
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- Rice, A. M., et al.
(author)
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Development and characterization of nine polymorphic microsatellite markers for Mexican spadefoot toads (Spea multiplicata) with cross-amplification in Plains spadefoot toads (S-bombifrons)
- 2008
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 8:6, s. 1386-1389
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Journal article (peer-reviewed)abstract
- We developed nine polymorphic microsatellite markers for the Mexican spadefoot toad, Spea multiplicata. Allele numbers range from five to 12, with observed heterozygosities from 0.48 to 0.87. Because two loci are in linkage disequilibrium, these nine loci provide eight independent markers. Three loci exhibit departure from Hardy-Weinberg equilibrium, possibly resulting from null alleles or population admixture. These markers will be useful for assessing population structure and relatedness in S. multiplicata. Based on our success at cross-amplification in the Plains spadefoot toad (Spea bombifrons), these loci also may be useful in this species with additional optimization.
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- Soranzo, Nicole, et al.
(author)
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A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 38-1182
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Journal article (peer-reviewed)abstract
- The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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