Abstract
Summary
The growing availability of genomewide polymorphism data has fueled interest in detecting diverse selective processes affecting population diversity. However, no model-based ...approaches exist to jointly detect and distinguish the two complementary processes of balancing and positive selection. We extend the BalLeRMix B-statistic framework described in Cheng and DeGiorgio (2020) for detecting balancing selection and present BalLeRMix+, which implements five B statistic extensions based on mixture models to robustly identify both types of selection. BalLeRMix+ is implemented in Python and computes the composite likelihood ratios and associated model parameters for each genomic test position.
Availability and implementation
BalLeRMix+ is freely available at https://github.com/bioXiaoheng/BallerMixPlus.
Supplementary information
Supplementary data are available at Bioinformatics online.
The major histocompatibility complex (MHC) loci are amongst the most polymorphic regions in the genomes of vertebrates. In the human population, thousands of MHC gene variants (alleles) exist that ...translate into distinct allotypes equipped with overlapping but unique peptide binding profiles. Understanding the differential structural and dynamic properties of MHC alleles and their interaction with critical regulators of peptide exchange bears the potential for more personalized strategies of immune modulation in the context of HLA-associated diseases.
Summary
Allogeneic individuals co‐exist during pregnancy in eutherian mammals. Maternal and fetal cells intermingle at the site of placental attachment in the uterus, where the arteries are remodeled ...to supply the fetus with oxygen and nutrients. This access by placental cells to the maternal supply line determines the growth and birth weight of the baby and is subject to stabilizing selection. Invading placental trophoblast cells express human leukocyte antigen class I ligands (HLA‐E, HLA‐G, and HLA‐C) for receptors on maternal uterine natural killer (NK) and myelomonocytic cells, CD94/NKG2, leukocyte immunoglobulin‐like receptor (LILR), and killer immunoglobulin receptor (KIR). Of these, only the KIR/HLA‐C system is highly polymorphic. Different combinations of maternal KIR and fetal HLA‐C variants are correlated with low birth weight and pre‐eclampsia or high birth weight and obstructed labor, the two extremes of the obstetric dilemma. This situation has arisen because of the evolution of bipedalism and subsequently, in the last million years, larger brains. At this point, the human system began to reach a balance between KIR A and KIR B haplotypes and C1 and C2 epitopes of HLA‐C alleles that reflects a functional compromise between the competing demands of immunity and reproduction.
Fundamental biological processes hinge on coordinated interactions between genes spanning two obligate genomes—mitochondrial and nuclear. These interactions are key to complex life, and allelic ...variation that accumulates and persists at the loci embroiled in such intergenomic interactions should therefore be subjected to intense selection to maintain integrity of the mitochondrial electron transport system. Here, we compile evidence that suggests that mitochondrial–nuclear (mitonuclear) allelic interactions are evolutionarily significant modulators of the expression of key health-related and life-history phenotypes, across several biological scales—within species (intra- and interpopulational) and between species. We then introduce a new frontier for the study of mitonuclear interactions—those that occur within individuals, and are fuelled by the mtDNA heteroplasmy and the existence of nuclear-encoded mitochondrial gene duplicates and isoforms. Empirical evidence supports the idea of high-resolution tissue- and environment-specific modulation of intraindividual mitonuclear interactions. Predicting the penetrance, severity and expression patterns of mtDNA-induced mitochondrial diseases remains a conundrum. We contend that a deeper understanding of the dynamics and ramifications of mitonuclear interactions, across all biological levels, will provide key insights that tangibly advance our understanding, not only of core evolutionary processes, but also of the complex genetics underlying human mitochondrial disease.
Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome ...variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.
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•The genomes of 1,135 naturally inbred lines of Arabidopsis thaliana are presented•Relict populations that continue to inhabit ancestral habitats were discovered•The last glacial maximum was important in structuring the distribution of relicts•This collection will connect genotypes and phenotypes on a species-wide level
Genomic sequencing analysis of over 1,000 natural inbred lines of Arabidopsis thaliana reveals its global population structure, migration patterns, and evolutionary history and provides a rich genetic resource for studying phenotypic variation and adaptation.
Rapid and precise screening of small genetic variations, such as single-nucleotide polymorphisms (SNPs), among an individual’s genome is still an unmet challenge at point-of-care settings. One ...crucial step toward this goal is the development of discrimination probes that require no enzymatic reaction and are easy to use. Here we report a new type of fluorescent molecular probe, termed a chameleon NanoCluster Beacon (cNCB), that lights up into different colors upon binding SNP targets. NanoCluster Beacons (NCBs) are collections of a small number of Ag atoms templated on single-stranded DNA that fluoresce strongly when placed in proximity to particular DNA sequences, termed enhancers. Here we show the fluorescence emission color of a NCB can change substantially (a shift of 60–70 nm in the emission maximum) depending upon the alignment between the silver nanocluster and the DNA enhancer sequence. Chameleon NCBs exploit this color shift to directly detect SNPs, based on the fact that different SNPs produce a different alignment between the Ag nanocluster and the enhancer. This SNP detection method has been validated on all single-nucleotide substitution scenarios in three synthetic DNA targets, in six disease-related SNP targets, and in two clinical samples taken from patients with ovarian serous borderline tumors. Samples with single-nucleotide variations can be easily identified by the naked eye under UV excitation, making this method a reliable and low-cost assay with a simple readout format.
Of the five immunoglobulin isotypes, immunoglobulin G (IgG) is most abundant in human serum. The four subclasses, IgG1, IgG2, IgG3, and IgG4, which are highly conserved, differ in their constant ...region, particularly in their hinges and upper CH2 domains. These regions are involved in binding to both IgG-Fc receptors (FcγR) and C1q. As a result, the different subclasses have different effector functions, both in terms of triggering FcγR-expressing cells, resulting in phagocytosis or antibody-dependent cell-mediated cytotoxicity, and activating complement. The Fc-regions also contain a binding epitope for the neonatal Fc receptor (FcRn), responsible for the extended half-life, placental transport, and bidirectional transport of IgG to mucosal surfaces. However, FcRn is also expressed in myeloid cells, where it participates in both phagocytosis and antigen presentation together with classical FcγR and complement. How these properties, IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function will be the focus of the current review.
Eco-Evolutionary Genomics of Chromosomal Inversions Wellenreuther, Maren; Bernatchez, Louis
Trends in ecology & evolution (Amsterdam),
June 2018, 2018-06-00, 20180601, Letnik:
33, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Chromosomal inversions have long fascinated evolutionary biologists due to their suppression of recombination, which can protect co-adapted alleles. Emerging research documents that inversions are ...commonly linked to spectacular phenotypes and have a pervasive role in eco-evolutionary processes, from mating systems, social organisation, environmental adaptation, and reproductive isolation to speciation. Studies also reveal that inversions are taxonomically widespread, with many being old and large, and that balancing selection is commonly facilitating their maintenance. This challenges the traditional view that the role of balancing selection in maintaining variation is relatively minor. The ubiquitous importance of inversions in ecological and evolutionary processes suggests that structural variation should be better acknowledged and integrated in studies pertaining to the molecular basis of adaptation and speciation.
Inversions are potent forces in local adaptation and diversification because they protect inverted sequences from recombination, allowing favourable allelic combination to be maintained in the face of gene flow.
High-throughput genomics methods have revived the popularity of research on inversions, and recent studies reveal that they are taxonomically more widespread than previously thought.
Inversions can be maintained over hundreds of thousands and even millions of years via various forms of balancing selection and often involve large genomic regions, each comprising hundreds of genes, together representing a significant portion of the genome.
The ubiquitous importance of inversions in ecological and evolutionary processes indicates that such structural variation must be better acknowledged and integrated in studies pertaining to the molecular basis of adaptation and speciation.
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