Pleiotropic effects on mandibular morphology II: differential epistasis and genetic variation in morphological integration

The evolution of morphological modularity through the sequestration of pleiotropy to sets of functionally and developmentally related traits requires genetic variation in the relationships between traits. Genetic variation in relationships between traits can result from differential epistasis, where epistatic relationships for pairs of loci are different for different traits. This study maps relationship quantitative trait loci (QTLs), specifically QTLs that affect the relationship between individual mandibular traits and mandible length, across the genome in an F2 intercross of the LG/J and SM/J inbred mouse strains (N = 1045). We discovered 23 relationship QTLs scattered throughout the genome. All mandibular traits were involved in one or more relationship QTL. When multiple traits were affected at a relationship QTL, the traits tended to come from a developmentally restricted region of the mandible, either the muscular processes or the alveolus. About one-third of the relationship QTLs correspond to previously located trait QTLs affecting the same traits. These results comprise examples of genetic variation necessary for an evolutionary response to selection on the range of pleiotropic effects.     

Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence

The neutral theory of molecular evolution predicts that the ratio of polymorphisms to fixed differences should be fairly uniform across a region of DNA sequence. Significant heterogeneity in this ratio can indicate the effects of balancing selection, selective sweeps, mildly deleterious mutations, or background selection. Comparing an observed heterogeneity statistic with simulations of the heterogeneity resulting from random phylogenetic and sampling variation provides a test of the statistical significance of the observed pattern. When simulated data sets containing heterogeneity in the polymorphism-to-divergence ratio are examined, different statistics are most powerful for detecting different patterns of heterogeneity. The number of runs is most powerful for detecting patterns containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic is most powerful for detecting patterns in which one end of the gene has high polymorphism and the other end has low polymorphism; and a newly developed statistic, the mean sliding G statistic, is most powerful for detecting patterns containing one or two peaks of polymorphism with reduced polymorphism on either side. Nine out of 27 genes from the Drosophila melanogaster subgroup exhibit heterogeneity that is significant under at least one of these three tests, with five of the nine remaining significant after a correction for multiple comparisons, suggesting that detectable evidence for the effects of some kind of selection is fairly common.      

Phylogeography and conservation genetics of a giant lobelia (Lobelia giberroa) in Ethiopian and Tropical East African mountains

Lobelia giberroa is a giant rosette plant growing in the afro-montane belt of the afro-alpine environment, a unique and little-studied ecosystem occupying the high mountains of eastern Africa. We analysed amplified fragment length polymorphisms (AFLPs) from 11 mountain systems in Ethiopia and Tropical East Africa to infer the phylogeographical history of the species. A total of 191 individuals were investigated from 25 populations. Principal coordinate analysis and population structure analyses revealed three major phylogeographical groups: the Ethiopian mountains and one group on each side of the Rift Valley in Tropical East Africa, respectively: Elgon-Cherangani and Kenya-Aberdare-Kilimanjaro-Meru. Analysis of Molecular Variance showed 55.7% variance among the three groups, suggesting an old divergence. Together with a clear geographical substructure within the main groups, this pattern indicates gradual expansion and supports the montane forest bridge hypothesis, stating that the area occupied by forest was larger and more continuous in previous interglacials and earlier in the present interglacial. Genetic diversity was lower in Ethiopia than in the other two main groups, possibly due to an ancient founder effect when Ethiopia was colonized from the south.     

Statistical analysis of amplified fragment length polymorphism data: a toolbox for molecular ecologists and evolutionists

Recently, the amplified fragment length polymorphism (AFLP) technique has gained a lot of popularity, and is now frequently applied to a wide variety of organisms. Technical specificities of the AFLP procedure have been well documented over the years, but there is on the contrary little or scattered information about the statistical analysis of AFLPs. In this review, we describe the various methods available to handle AFLP data, focusing on four research topics at the population or individual level of analysis: (i) assessment of genetic diversity; (ii) identification of population structure; (iii) identification of hybrid individuals; and (iv) detection of markers associated with phenotypes. Two kinds of analysis methods can be distinguished, depending on whether they are based on the direct study of band presences or absences in AFLP profiles ('band-based' methods), or on allelic frequencies estimated at each locus from these profiles ('allele frequency-based' methods). We investigate the characteristics and limitations of these statistical tools; finally, we appeal for a wider adoption of methodologies borrowed from other research fields, like for example those especially designed to deal with binary data.     

Predation Hot Spots: Large Scale Impact of Local Aggregations

Abstract   Broad scale survey distributions of fish are dominated by some extremely high catches. With a novel survey design we resolved the small-scale fish distribution in the spatio-temporal vicinity of these extreme hauls and showed that in the North Sea they generally do not occur in isolation. An additional case study where stomach contents of fish predators were analyzed revealed that they actually indicate aggregations of piscivorous fish predators on prey aggregations. We show that the predation impact can reach immense dimensions, an aggregation of more than 50 million juvenile cod (Gadus morhua) was entirely wiped out in 5 days by predatory whiting (Merlangius merlangus), aggregating on these juveniles in an area of approximately 18 km². The consumption of only 32 hot spots of similar magnitude as observed in our study adds up to the average size of an incoming North Sea cod year class. These findings support the hypothesis of predation as the major source of mortality in young-of-the-year demersal fish species and questions the generality of fish aggregation as an effective anti-predator strategy. This study highlights the system-wide structuring force of small-scale predation hot spots and further points to the importance of a more realistic implementation of local high-intensity predation events in food web models. Electronic supplementary material:   The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Whole genome bisulfite sequencing of cell-free DNA and its cellular contributors uncovers placenta hypomethylated domains

BackgroundCirculating cell-free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the maternal and fetal DNA. Testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA; however, this depends on knowledge of the methylomes of circulating cell-free DNA and its cellular contributors.ResultsWe perform whole genome bisulfite sequencing on a set of unmatched samples including circulating cell-free DNA from non-pregnant and pregnant female donors and genomic DNA from maternal buffy coat and placenta samples. We find CpG cytosines within longer fragments are more likely to be methylated. Comparison of the methylomes of placenta and non-pregnant circulating cell-free DNA reveal many of the 51,259 identified differentially methylated regions are located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases. We find these placenta hypomethylated domains are consistently located within regions exhibiting low CpG and gene density. Differentially methylated regions identified when comparing placenta to non-pregnant circulating cell-free DNA are recapitulated in pregnant circulating cell-free DNA, confirming the ability to detect differential methylation in circulating cell-free DNA mixtures.ConclusionsWe generate methylome maps for four sample types at single-base resolution, identify a link between DNA methylation and fragment length in circulating cell-free DNA, identify differentially methylated regions between sample groups, and uncover the presence of megabase-size placenta hypomethylated domains.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0645-x) contains supplementary material, which is available to authorized users.     

Diet‐Dependent Genetic and Genomic Imprinting Effects on Obesity in Mice

Although the current obesity epidemic is of environmental origin, there is substantial genetic variation in individual response to an obesogenic environment. In this study, we perform a genome‐wide scan for quantitative trait loci (QTLs) affecting obesity per se, or an obese response to a high‐fat diet in mice from the LG/J by SM/J Advanced Intercross (AI) Line (Wustl:LG, SM‐G16). A total of 1,002 animals from 78 F₁₆ full sibships were weaned at 3 weeks of age and half of each litter placed on high‐ and low‐fat diets. Animals remained on the diet until 20 weeks of age when they were necropsied and the weights of the reproductive, kidney, mesenteric, and inguinal fat depots were recorded. Effects on these phenotypes, along with total fat depot weight and carcass weight at necropsy, were mapped across the genome using 1,402 autosomal single‐nucleotide polymorphism (SNP) markers. Haplotypes were reconstructed and additive, dominance, and imprinting genotype scores were derived every 1 cM along the F₁₆ map. Analysis was performed using a mixed model with additive, dominance, and imprinting genotype scores, their interactions with sex, diet, and with sex‐by‐diet as fixed effects and with family and its interaction with sex, diet, and sex‐by‐diet as random effects. We discovered 95 trait‐specific QTLs mapping to 40 locations. Most QTLs had additive effects with dominance and imprinting effects occurring at two‐thirds of the loci. Nearly every locus interacted with sex and/or diet in important ways demonstrating that gene effects are primarily context dependent, changing depending on sex and/or diet.