How Quaternary climatic oscillations affected range distributions and intraspecific divergence of alpine plants on the Qinghai-Tibetan Plateau (QTP) remains largely unknown. Here, we report a survey of chloroplast DNA (cpDNA) and nuclear ribosomal internal transcribed spacer (ITS) DNA variation aimed at exploring the phylogeographical history of the QTP alpine endemic Aconitum gymnandrum. We sequenced three cpDNA fragments (rpl20-rps12 intergenic spacer, the trnV intron and psbA-trnH spacer) and also the nuclear (ITS) region in 245 individuals from 23 populations sampled throughout the species' range. Two distinct lineages, with eastern and western geographical distributions respectively, were identified from a phylogenetic analysis of ITS sequence variation. Based on a fast substitution rate, these were estimated to have diverged from each other in the early Pleistocene approximately 1.45 Ma. The analysis of cpDNA variation identified nine chlorotypes that clustered into two major clades that were broadly congruent in geographical distribution with the two ITS lineages. The east-west split of cpDNA divergence was supported by an amova which partitioned approximately half of the total variance between these two groups of populations. Analysis of the spatial distribution of chlorotypes showed that each clade was subdivided into two groups of populations such that a total of four population groups existed in the species. It is suggested that these different groups derive from four independent glacial refugia that existed during the Last Glacial Maximum (LGM), and that three of these refugia were located at high altitude on the QTP platform itself at that time. Coalescent simulation of chlorotype genealogies supported both an early Pleistocene origin of the two main cpDNA clades and also the 'four-refugia' hypothesis during the LGM. Two previous phylogeographical studies of QTP alpine plants indicated that such plants retreated to refugia at the eastern/south-eastern plateau edge during the LGM and/or previous glacial maxima. However, the results for A. gymnandrum suggest that at least some of these cold-tolerant species may have also survived centrally on the QTP platform throughout the Quaternary.

Species within the human pathogenic Cryptococcus species complex are major threats to public health, causing approximately 1 million annual infections globally. Cryptococcus amylolentus is the most closely known related species of the pathogenic Cryptococcus species complex, and it is non-pathogenic. Additionally, while pathogenic Cryptococcus species have bipolar mating systems with a single large mating type (MAT) locus that represents a derived state in Basidiomycetes, C. amylolentus has a tetrapolar mating system with 2 MAT loci (P/R and HD) located on different chromosomes. Thus, studying C. amylolentus will shed light on the transition from tetrapolar to bipolar mating systems in the pathogenic Cryptococcus species, as well as its possible link with the origin and evolution of pathogenesis. In this study, we sequenced, assembled, and annotated the genomes of 2 C. amylolentus isolates, CBS6039 and CBS6273, which are sexual and interfertile. Genome comparison between the 2 C. amylolentus isolates identified the boundaries and the complete gene contents of the P/R and HD MAT loci. Bioinformatic and chromatin immunoprecipitation sequencing (ChIP-seq) analyses revealed that, similar to those of the pathogenic Cryptococcus species, C. amylolentus has regional centromeres (CENs) that are enriched with species-specific transposable and repetitive DNA elements. Additionally, we found that while neither the P/R nor the HD locus is physically closely linked to its centromere in C. amylolentus, and the regions between the MAT loci and their respective centromeres show overall synteny between the 2 genomes, both MAT loci exhibit genetic linkage to their respective centromere during meiosis, suggesting the presence of recombinational suppressors and/or epistatic gene interactions in the MAT-CEN intervening regions. Furthermore, genomic comparisons between C. amylolentus and related pathogenic Cryptococcus species provide evidence that multiple chromosomal rearrangements mediated by intercentromeric recombination have occurred during descent of the 2 lineages from their common ancestor. Taken together, our findings support a model in which the evolution of the bipolar mating system was initiated by an ectopic recombination event mediated by similar repetitive centromeric DNA elements shared between chromosomes. This translocation brought the P/R and HD loci onto the same chromosome, and further chromosomal rearrangements then resulted in the 2 MAT loci becoming physically linked and eventually fusing to form the single contiguous MAT locus that is now extant in the pathogenic Cryptococcus species.

Studies of a hybrid zone between two house mouse subspecies (Mus musculus musculus and M. m. domesticus) along with studies using laboratory crosses reveal a large role for the X chromosome and multiple autosomal regions in reproductive isolation as a consequence of disrupted epistasis in hybrids. One limitation of previous work has been that most of the identified genomic regions have been large. The goal here is to detect and characterize precise genomic regions underlying reproductive isolation. We surveyed 1401 markers evenly spaced across the genome in 679 mice collected from two different transects. Comparisons between transects provide a means for identifying common patterns that likely reflect intrinsic incompatibilities. We used a genomic cline approach to identify patterns that correspond to epistasis. From both transects, we identified contiguous regions on the X chromosome in which markers were inferred to be involved in epistatic interactions. We then searched for autosomal regions showing the same patterns and found they constitute about 5% of autosomal markers. We discovered substantial overlap between these candidate regions underlying reproductive isolation and QTL for hybrid sterility identified in laboratory crosses. Analysis of gene content in these regions suggests a key role for several mechanisms, including the regulation of transcription, sexual conflict and sexual selection operating at both the postmating prezygotic and postzygotic stages of reproductive isolation. Taken together, these results indicate that speciation in two recently diverged (c. 0.5 Ma) house mouse subspecies is complex, involving many genes dispersed throughout the genome and associated with distinct functions.

Multiple Sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7 receptor alpha chain gene (sIL7R), produced by alternative splicing of IL7R exon 6. Here, we identified the RNA helicase DDX39B as a potent activator of this exon and consequently a repressor of sIL7R, and found strong genetic association of DDX39B with MS risk. Indeed, we showed that a genetic variant in the 5′ UTR of DDX39B reduces translation of DDX39B mRNAs and increases MS risk. Importantly, this DDX39B variant showed strong genetic and functional epistasis with allelic variants in IL7R exon 6. This study establishes the occurrence of biological epistasis in humans and provides mechanistic insight into the regulation of IL7R exon 6 splicing and its impact on MS risk.

Aim  Palaeontologial data suggest that all temperate forest species in northern China migrated southwards during the Last Glacial Maximum (LGM) and recolonized post‐glacially within the Holocene. We tested this assumption using phylogeographical studies of a temperate deciduous shrub species (Ostryopsis davidiana Decne., Betulaceae), which has a wide distribution in northern China. Location  Northern China. Methods  We sequenced two chloroplast DNA (cpDNA) fragments (trnL–trnF and psbA–trnH, together about 1300 bp in length) of 294 plants from 21 populations across the total distribution range of this species. We used maximum parsimony and haplotype network methods to construct phylogenetic relationships among haplotypes. Results  The analysis of cpDNA variation identified eight haplotypes. A single haplotype was fixed in all populations except for one population that was polymorphic, having two haplotypes. The population subdivisions were extremely high (GST = 0.972 and NST = 0.974), suggesting very low gene flow between populations. Haplotypes clustered into two tentative clades, both of which occur in the southern region of the species’ range but only one of which occurs in the northern region. Across the sampled populations, the haplotype distributions were differentiated geographically. Main conclusions  Our analyses suggest that multiple refugia were maintained across the range of O. davidiana in both northern (north of the Qing Mountains) and southern (south of the Qing Mountains) regions during the LGM rather than that the species survived only in the south and subsequently colonized northwards. The extremely low within‐population diversity of this species suggests strong bottleneck or founder effects within each fragmented region during the Quaternary climatic oscillations. These findings provide important clues for understanding range shifts and changes in within‐ and/or between‐population genetic diversity of temperate forests in response to past climatic oscillations in northern China.

Increasing evidence suggests that geological or climatic events in the past promoted allopatric speciation of alpine plants in the Qinghai-Tibetan Plateau and adjacent region. However, few studies have been undertaken to examine whether such allopatric divergences also occurred within a morphologically uniform species. In the present study, we report the evolutionary history of an alpine shrub species, Hippophae tibetana, based on examining chloroplast DNA (cpDNA) and nuclear ribosomal internal transcribed spacer (ITS) DNA variations. We sequenced two cpDNA fragments (trnL-F and trnS-G) and the nuclear ITS region in 183 individuals collected from 21 natural populations. Ten chlorotypes and 17 ITS types were identified. Phylogenetic analyses of both chlorotypes and ITS sequence variations suggested two distinct lineages distributed in the eastern and western region, respectively. On the basis of the fast and low plant substitution rates, these two lineages were estimated to have diverged from each other between 1 and 4 million years ago, during the period of the major glaciations and orogenic processes. In addition, ITS has undergone the accelerated evolution in two populations in the southern Himalaya isolated by the high mountains with a surprising accumulation of the private variations. The east-west split was also supported by an analysis of molecular variance, which partitioned around 91% of the total cpDNA variance between these two groups of populations. A single chlorotype was found for most populations in eastern or western region, suggesting a recent postglacial expansion within each region. Star-phylogeny and mismatch analyses of all chlorotypes within the eastern group of populations suggested an earlier regional expansion before the Last Glacial Maximum (LGM). The local fixture of the different chlorotypes in multiple populations suggested more than one refugia remained for eastern or western region. Coalescent tests rejected the hypothesis that all current populations originated from a single refugium during the LGM. Instead, they supported hypothesis that two lineages diverged before the late Pleistocene. These findings, when taken together, suggested that this species had experienced long allopatric divergence and recent regional range expansions in response to orogenic processes and the climate changes. The evolutionary history of this shrub species highlights importance of geographical isolations to the intraspecific divergence of alpine plants occurring in the world's ruff.

Genomic features such as rate of recombination and differentiation have been suggested to play a role in species divergence. However, the relationship of these phenomena to functional organization of the genome in the context of reproductive isolation remains unexplored. Here, we examine genomic characteristics of the species boundaries between two house mouse subspecies (Mus musculus musculus/M. m. domesticus). These taxa form a narrow semipermeable zone of secondary contact across Central Europe. Due to the incomplete nature of reproductive isolation, gene flow in the zone varies across the genome. We present an analysis of genomic differentiation, rate of recombination, and functional composition of genes relative to varying amounts of introgression. We assessed introgression using 1,316 autosomal single nucleotide polymorphism markers, previously genotyped in hybrid populations from three transects. We found a significant relationship between amounts of introgression and both genomic differentiation and rate of recombination with genomic regions of reduced introgression associated with higher genomic differentiation and lower rates of recombination, and the opposite for genomic regions of extensive introgression. We also found a striking functional polarization of genes based on where they are expressed in the cell. Regions of elevated introgression exhibit a disproportionate number of genes involved in signal transduction functioning at the cell periphery, among which olfactory receptor genes were found to be the most prominent group. Conversely, genes expressed intracellularly and involved in DNA binding were the most prevalent in regions of reduced introgression. We hypothesize that functional organization of the genome is an important driver of species divergence.

To date, little is still known about how alpine species occurring in the Qinghai-Tibetan Plateau (QTP) responded to past climatic oscillations. Here, by using variations of the chloroplast trnT-L, we examined the genetic distribution pattern of 101 individuals of Potentilla glabra, comprising both the interior QTP and the plateau edge. Phylogenetic and network analyses of 31 recovered haplotypes identified three tentative clades (A, B and C). Analysis of molecular variance (amova) revealed that most of the genetic variability was found within populations (0.693), while differentiations between populations were obviously distinct (F(st)= 0.307). Two independent range expansions within clades A and B occurring at approximately 316 and 201 thousand years ago (kya) were recovered from the hierarchical mismatch analysis, and these two expansions were also confirmed by Fu's F(S) values and 'g' tests. However, distant distributions of clade C and private haplotypes from clades A and B suggest that they had survived the Last Glacial Maximum (LGM) and previous glaciers in situ since their origins. Our findings based on available limited samples support that multiple refugia of a few cold-enduring species had been maintained in the QTP platform during LGM and/or previous glacial stages.