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Y chromosomes are typically viewed as genetic wastelands with few intact genes. Recent genomic analyses in Drosophila, however, show that gene gain is prominent on young Y chromosomes. Meiosis- and RNAi-related genes often coamplify on recently formed X and Y chromosomes, are testis-expressed, and produce antisense transcripts and short RNAs. RNAi pathways are also involved in suppressing sex ratio drive in Drosophila. These observations paint a dynamic picture of sex chromosome differentiation, suggesting that rapidly evolving genomic battles over segregation are rampant on young sex chromosomes and utilize RNAi to defend the genome against selfish elements that manipulate fair meiosis. Recurrent sex chromosome drive can have profound ecological, evolutionary, and cellular impacts and account for unique features of sex chromosomes.

Summary: A major reason for studying plant sex chromosomes is that they may often be 'young' systems. There is considerable evidence for the independent evolution of separate sexes within plant families or genera, in some cases showing that the maximum possible time during which their sex‐determining genes have existed must be much shorter than those of several animal taxa. Consequently, their sex‐linked regions could either have evolved soon after genetic sex determination arose or considerably later. Plants, therefore, include species with both young and old systems. I review several questions about the evolution of sex‐determining systems and sex chromosomes that require studies of young systems, including: the kinds of mutations involved in the transition to unisexual reproduction from hermaphroditism or monoecy (a form of functional hermaphroditism); the times when they arose; and the extent to which the properties of sex‐linked regions of genomes reflect responses to new selective situations created by the presence of a sex‐determining locus. I also evaluate which questions are best studied in plants, vs other suitable candidate organisms. Studies of young plant systems can help understand general evolutionary processes that are shared with the sex chromosomes of other organisms. [ABSTRACT FROM AUTHOR]

Microbial endosymbiosis is widespread in animals, with major ecological and evolutionary implications. Successful symbiosis relies on efficient vertical transmission through host generations. However, when symbionts negatively affect host fitness, hosts are expected to evolve suppression of symbiont effects or transmission. Here, we show that sex chromosomes control vertical transmission of feminizing Wolbachia endosymbionts in the isopod Armadillidium nasatum. Theory predicts that the invasion of an XY/XX species by cytoplasmic sex ratio distorters is unlikely because it leads to fixation of the unusual (and often lethal or infertile) YY genotype. We demonstrate that A. nasatum X and Y sex chromosomes are genetically highly similar and that YY individuals are viable and fertile, thereby enabling Wolbachia spread in this XY-XX species. Nevertheless, we show that Wolbachia cannot drive fixation of YY individuals, because infected YY females do not transmit Wolbachia to their offspring, unlike XX and XY females. The genetic basis fits the model of a Y-linked recessive allele (associated with an X-linked dominant allele), in which the homozygous state suppresses Wolbachia transmission. Moreover, production of all-male progenies by infected YY females restores a balanced sex ratio at the host population level. This suggests that blocking of Wolbachia transmission by YY females may have evolved to suppress feminization, thereby offering a whole new perspective on the evolutionary interplay between microbial symbionts and host sex chromosomes. [ABSTRACT FROM AUTHOR]

The Y chromosome harbors nine multi-copy ampliconic gene families expressed exclusively in testis. The gene copies within each family are >99% identical to each other, which poses a major challenge in evaluating their copy number. Recent studies demonstrated high variation in Y ampliconic gene copy number among humans. However, how this variation affects expression levels in human testis remains understudied. Here we developed a novel computational tool Ampliconic Copy Number Estimator (AmpliCoNE) that utilizes read sequencing depth information to estimate Y ampliconic gene copy number per family. We applied this tool to whole-genome sequencing data of 149 men with matched testis expression data whose samples are part of the Genotype-Tissue Expression (GTEx) project. We found that the Y ampliconic gene families with low copy number in humans were deleted or pseudogenized in non-human great apes, suggesting relaxation of functional constraints. Among the Y ampliconic gene families, higher copy number leads to higher expression. Within the Y ampliconic gene families, copy number does not influence gene expression, rather a high tolerance for variation in gene expression was observed in testis of presumably healthy men. No differences in gene expression levels were found among major Y haplogroups. Age positively correlated with expression levels of the HSFY and PRY gene families in the African subhaplogroup E1b, but not in the European subhaplogroups R1b and I1. We also found that expression of five out of six Y ampliconic gene families is coordinated with that of their non-Y (i.e. X or autosomal) homologs. Indeed, five ampliconic gene families had consistently lower expression levels when compared to their non-Y homologs suggesting dosage regulation, while the HSFY family had higher expression levels than its X homolog and thus lacked dosage regulation. [ABSTRACT FROM AUTHOR]

Silene latifolia is a dioecious flowering plant with sex chromosomes in the family Caryophyllaceae. Development of a gynoecium and stamens are suppressed in the male and female flowers of S. latifolia, respectively. Microbotryum lychnidis-dioicae promotes stamen development when it infects the female flower. If suppression of the stamen and gynoecium development is regulated by the same mechanism, suppression of gynoecium and stamen development is released simultaneously with the infection by M. lychnidis-dioicae. To assess this hypothesis, an asexual mutant without a gynoecium or stamen was infected with M. lychnidis-dioicae. A filament of the stamen in the infected asexual mutant was elongated at stages 11 and 12 of flower bud development as well as in the male, but the gynoecium did not form. Instead of the gynoecium, a filamentous structure was suppressed as in the male flower. Developmental suppression of the stamen was released by M. lychnidis-dioicae, but that of gynoecium development was not released. M. lychnidis-dioicae would have a function similar to stamen-promoting factor (SPF), since the elongation of the stamen that is not observed in the healthy asexual mutant was observed after stage 8 of flower bud development. An infection experiment also revealed that a deletion on the Y chromosome of the asexual mutant eliminated genes for maturation of tapetal cells because the tapetal cells did not mature in the asexual mutant infected with M. lychnidis-dioicae. [ABSTRACT FROM AUTHOR]

In most mammals, the male to female sex ratio of offspring is about 50% because half of the sperm contain either the Y chromosome or X chromosome. In mice, the Y chromosome encodes fewer than 700 genes, whereas the X chromosome encodes over 3,000 genes. Although overall gene expression is lower in sperm than in somatic cells, transcription is activated selectively in round spermatids. By regulating the expression of specific genes, we hypothesized that the X chromosome might exert functional differences in sperm that are usually masked during fertilization. In this study, we found that Toll-like receptors 7/8 (TLR7/8) coding the X chromosome were expressed by approximately 50% of the round spermatids in testis and in approximately 50% of the epididymal sperm. Especially, TLR7 was localized to the tail, and TLR8 was localized to the midpiece. Ligand activation of TLR7/8 selectively suppressed the mobility of the X chromosome–bearing sperm (X-sperm) but not the Y-sperm without altering sperm viability or acrosome formation. The difference in sperm motility allowed for the separation of Y-sperm from X-sperm. Following in vitro fertilization using the ligand-selected high-mobility sperm, 90% of the embryos were XY male. Likewise, 83% of the pups obtained following embryo transfer were XY males. Conversely, the TLR7/8-activated, slow mobility sperm produced embryos and pups that were 81% XX females. Therefore, the functional differences between Y-sperm and X-sperm motility were revealed and related to different gene expression patterns, specifically TLR7/8 on X-sperm. [ABSTRACT FROM AUTHOR]

Y chromosomes often contain amplified genes which can increase dosage of male fertility genes and counteract degeneration via gene conversion. Here we identify genes with increased copy number on both X and Y chromosomes in various species of Drosophila, a pattern that has previously been associated with sex chromosome drive involving the Slx and Sly gene families in mice. We show that recurrent X/Y co-amplification appears to be an important evolutionary force that has shaped gene content evolution of sex chromosomes in Drosophila. We also demonstrate that convergent acquisition and amplification of testis expressed gene families are common on Drosophila sex chromosomes, and especially on recently formed ones, and we carefully characterize one putative novel X/Y co-amplification system. We find that co-amplification of the S-Lap1/GAPsec gene pair on both the X and the Y chromosome occurred independently several times in members of the D. obscura group, where this normally autosomal gene pair is sex-linked due to a sex chromosome—autosome fusion. We explore several evolutionary scenarios that would explain this pattern of co-amplification. Investigation of gene expression and short RNA profiles at the S-Lap1/GAPsec system suggest that, like Slx/Sly in mice, these genes may be remnants of a cryptic sex chromosome drive system, however additional transgenic experiments will be necessary to validate this model. Regardless of whether sex chromosome drive is responsible for this co-amplification, our findings suggest that recurrent gene duplications between X and Y sex chromosomes could have a widespread effect on genomic and evolutionary patterns, including the epigenetic regulation of sex chromosomes, the distribution of sex-biased genes, and the evolution of hybrid sterility. [ABSTRACT FROM AUTHOR]

Sex chromosomes stop recombining and accumulate differences over time. In particular, genes on the chromosome restricted to the heterogametic sex degenerate and become non-functional. Here, we investigated whether or not the degeneration of a plant Y chromosome was sufficient to cause ovules containing a Y to fail to develop, thereby eliminating the possibility of YY individuals. We used two genotypic assays to determine the genotype—XX, XY, or YY—of offspring from a single fruit of an otherwise normal male XY plant of Silene latifolia. The fruit contained fewer ovules than normal pistillate flowers, produced an equal offspring sex ratio, and generated no YY offspring. The results indicate that ovaries must contain an X chromosome to develop properly. While haploid selection has slowed down Y-chromosome degeneration in S. latifolia, we find that it has progressed sufficiently to prevent the proper development of ovules, and hence prevent the presence of YY individuals. [ABSTRACT FROM AUTHOR]

Dioecy has evolved recently and independently from cosexual populations in many angiosperm lineages, providing opportunities to understand the evolutionary process underlying this transition. Spinach (Spinacia oleracea) is a dioecious plant with homomorphic sex chromosomes (XY). Although most of the spinach Y chromosome recombines with the X chromosome, a region around the male-determining locus on Y does not recombine with its X counterpart, suggesting that this region might be related to the evolution of dioecy in the species. To identify genes located in the non-recombining region (MSY, male-specific region of Y), RNA-seq analysis of male and female progeny plants (eight each) from a sib-cross of a dioecious line was performed. We discovered only 354 sex-chromosomal SNPs in 219 transcript sequences (genes). We randomly selected 39 sex-chromosomal genes to examine the reproducibility of the RNA-seq results and observed tight linkage to the male-determining locus in a spinach segregating population (140 individuals). Further analysis using a large-scale population (>1400) and over 100 spinach germplasm accessions and cultivars showed that SNPs in at least 12 genes are fully linked to the male-determining locus, suggesting that the genes reside in the spinach MSY. Synonymous substitution rates of the MSY genes and X homologues predict a recent divergence (0.40 ± 0.08 Mya). Furthermore, synonymous divergence between spinach and its wild relative (S. tetrandra), whose sex chromosomes (XY) originated from a common ancestral chromosome, predicted that the species diverged around 5.7 Mya. Assuming that dioecy in Spinacia evolved before speciation within the genus and has a monophyletic origin, our data suggest that recombination around the spinach sex-determining locus might have stopped significantly later than the evolution of dioecy in Spinacia. [ABSTRACT FROM AUTHOR]

The reliquary of Jacques de Vitry, a prominent clergyman and theologian in the early 13th century, has experienced several transfers over the last centuries, which seriously question the attribution of the remains to the late Cardinal. Uncertainty about the year of his birth poses an additional question regarding his age at death in 1240. The reliquary, located in the Saint Marie d’Oigines church, Belgium, was reopened in 2015 for an interdisciplinary study around his relics as well as the Treasure of Oignies, a remarkable cultural heritage notably built from Jacques de Vitry’s donation. Anthropological, isotopic and genetic analyses were performed independently on the remains found in the reliquary. Results of the analyses provided evidence that the likelihood that these remains are those of Jacques de Vitry is very high: the remains belong to the same human male individual and the historical tradition about his age is confirmed. In addition, a separate relic (left tibia) was analysed and found to match with the remains of the reliquary (right tibia). The unique Jacques de Vitry’s mitre, made of parchment, was sampled non-destructively and the extracted parchment collagen was analysed by a proteomic method in order to determine the animal species. The results showed that, surprisingly, not all parts of the mitre were made from the same species. All together, these findings are expected to fertilize knowledge carried by historical tradition around the relics of Jacques de Vitry and his related cultural heritage. [ABSTRACT FROM AUTHOR]

When divided by a given mutation rate, the ρ (rho) statistic provides a simple estimator of the age of a clade within a phylogenetic tree by averaging the number of mutations from each sample in the clade to its root. However, a long-standing critique of the use of ρ in genetic dating has been quite often cited. Here we show that the critique is unfounded. We demonstrate by a formal mathematical argument and illustrate with a simulation study that ρ estimates are unbiased and also that ρ and maximum likelihood estimates do not differ in any systematic fashion. We also demonstrate that the claim that the associated confidence intervals commonly estimate the uncertainty inappropriately is flawed since it relies on a means of calculating standard errors that is not used by any other researchers, whereas an established expression for the standard error is largely unproblematic. We conclude that ρ dating, alongside approaches such as maximum likelihood (ML) and Bayesian inference, remains a useful tool for genetic dating. [ABSTRACT FROM AUTHOR]

The valley of the Magdalena River is one of the main population pathways in Colombia. The gene pool and spatial configuration of human groups in this territory have been outlined throughout three historical stages: the Native pre-Hispanic world, Spanish colonization, and XIX century migrations. This research was designed with the goal of characterizing the diversity and distribution pattern of Y-chromosome lineages that are currently present in the Tolima and Huila departments (middle Magdalena River region). Historic cartography was used to identify the main geographic sites where the paternal lineages belonging to this area have gathered. Twelve municipalities were chosen, and a survey that included genealogical information was administered. Samples collected from 83 male volunteers were analyzed for 48 Y-SNPs and 17 Y-STRs. The results showed a highly diverse region characterized by the presence of 16 sublineages within the major clades R, Q, J, G, T and E and revealed that 93% (n = 77) of haplotypes were different. Among these haplogroups, European-specific R1b-M269 lineages were the most representative (57.83%), with six different subhaplogroups and 43 unique haplotypes. Native American paternal ancestry was also detected based on the presence of the Q1a2-M3*(xM19, M194, M199) and Q1a2-M346*(xM3) lineages. Interestingly, all Q1a2-M346*(xM3) samples (n = 7, with five different haplotypes) carried allele six at the DYS391 locus. This allele has a worldwide frequency of 0.169% and was recently associated with a new Native subhaplogroup. An in-depth phylogenetic analysis of these samples suggests the Tolima and Huila region to be the principal area in all Central and South America where this particular Native lineage is found. This lineage has been present in the region for at least 1,809 (+/- 0,5345) years. [ABSTRACT FROM AUTHOR]

Y chromosomes are widely believed to evolve from a normal autosome through a process of massive gene loss (with preservation of some male genes), shaped by sex-antagonistic selection and complemented by occasional gains of male-related genes. The net result of these processes is a male-specialized chromosome. This might be expected to be an irreversible process, but it was found in 2005 that the Drosophila pseudoobscura Y chromosome was incorporated into an autosome. Y chromosome incorporations have important consequences: a formerly male-restricted chromosome reverts to autosomal inheritance, and the species may shift from an XY/XX to X0/XX sex-chromosome system. In order to assess the frequency and causes of this phenomenon we searched for Y chromosome incorporations in 400 species from Drosophila and related genera. We found one additional large scale event of Y chromosome incorporation, affecting the whole montium subgroup (40 species in our sample); overall 13% of the sampled species (52/400) have Y incorporations. While previous data indicated that after the Y incorporation the ancestral Y disappeared as a free chromosome, the much larger data set analyzed here indicates that a copy of the Y survived as a free chromosome both in montium and pseudoobscura species, and that the current Y of the pseudoobscura lineage results from a fusion between this free Y and the neoY. The 400 species sample also showed that the previously suggested causal connection between X-autosome fusions and Y incorporations is, at best, weak: the new case of Y incorporation (montium) does not have X-autosome fusion, whereas nine independent cases of X-autosome fusions were not followed by Y incorporations. Y incorporation is an underappreciated mechanism affecting Y chromosome evolution; our results show that at least in Drosophila it plays a relevant role and highlight the need of similar studies in other groups. [ABSTRACT FROM AUTHOR]

The human X and Y chromosomes are heteromorphic but share a region of homology at the tips of their short arms, pseudoautosomal region 1 (PAR1), that supports obligate crossover in male meiosis. Although the boundary between pseudoautosomal and sex-specific DNA has traditionally been regarded as conserved among primates, it was recently discovered that the boundary position varies among human males, due to a translocation of ~110 kb from the X to the Y chromosome that creates an extended PAR1 (ePAR). This event has occurred at least twice in human evolution. So far, only limited evidence has been presented to suggest this extension is recombinationally active. Here, we sought direct proof by examining thousands of gametes from each of two ePAR-carrying men, for two subregions chosen on the basis of previously published male X-chromosomal meiotic double-strand break (DSB) maps. Crossover activity comparable to that seen at autosomal hotspots was observed between the X and the ePAR borne on the Y chromosome both at a distal and a proximal site within the 110-kb extension. Other hallmarks of classic recombination hotspots included evidence of transmission distortion and GC-biased gene conversion. We observed good correspondence between the male DSB clusters and historical recombination activity of this region in the X chromosomes of females, as ascertained from linkage disequilibrium analysis; this suggests that this region is similarly primed for crossover in both male and female germlines, although sex-specific differences may also exist. Extensive resequencing and inference of ePAR haplotypes, placed in the framework of the Y phylogeny as ascertained by both Y microsatellites and single nucleotide polymorphisms, allowed us to estimate a minimum rate of crossover over the entire ePAR region of 6-fold greater than genome average, comparable with pedigree estimates of PAR1 activity generally. We conclude ePAR very likely contributes to the critical crossover function of PAR1. [ABSTRACT FROM AUTHOR]

The rarity of human remains makes it difficult to apprehend the first settlements in Corsica. It is admitted that initial colonization could have occurred during the Mesolithic period when glaciations would have shortened the open water travel distance from the continent. Mesolithic sites in Corsica show relatively short and irregular occupation, and suggest discontinuous settling of very mobile groups probably traveling by boat. Previous genetic studies on Corsican populations showed internal differentiation and a relatively poor genetic relationship with continental populations, despite intense historical contacts, however local Mesolithic-based genetic inheritance has never been properly estimated. The aim of this study was to explore the Corsican genetic profile of Y-chromosomes in order to trace the genetic signatures back to the first migrations to Corsica. This study included 321 samples from men throughout Corsica; samples from Provence and Tuscany were added to the cohort. All samples were typed for 92 Y-SNPs, and Y-STRs were also analyzed. Results revealed highly differentiated haplogroup patterns among Corsican populations. Haplogroup G had the highest frequency in Corsica, mostly displaying a unique Y-STR profile. When compared with Provence and Tuscany, Corsican populations displayed limited genetic proximity. Corsican populations present a remarkable Y-chromosome genetic mixture. Although the Corsican Y-chromosome profile shows similarities with both Provence and to a lesser extent Tuscany, it mainly displays its own specificity. This study confirms the high level of genetic diversity in Corsican populations and backs genetic contributions from prehistoric migrations associated with the Mesolithic, Neolithic and Metal Age eras, rather than from historical movements to Corsica, respectively attested by frequencies and TMRCA of haplogroups G2a-L91 and G2a-P15, J2a-M241 and J2-DYS445 = 6, R1b-U152 and R1b-U106. These results suggest that marine routes to reach the Corsican coast in many different points may have led to such a genetic heterogeneity. [ABSTRACT FROM AUTHOR]

While short-read sequencing technology has resulted in a sharp increase in the number of species with genome assemblies, these assemblies are typically highly fragmented. Repeats pose the largest challenge for reference genome assembly, and pericentromeric regions and the repeat-rich Y chromosome are typically ignored from sequencing projects. Here, we assemble the genome of Drosophila miranda using long reads for contig formation, chromatin interaction maps for scaffolding and short reads, and optical mapping and bacterial artificial chromosome (BAC) clone sequencing for consensus validation. Our assembly recovers entire chromosomes and contains large fractions of repetitive DNA, including about 41.5 Mb of pericentromeric and telomeric regions, and >100 Mb of the recently formed highly repetitive neo-Y chromosome. While Y chromosome evolution is typically characterized by global sequence loss and shrinkage, the neo-Y increased in size by almost 3-fold because of the accumulation of repetitive sequences. Our high-quality assembly allows us to reconstruct the chromosomal events that have led to the unusual sex chromosome karyotype in D. miranda, including the independent de novo formation of a pair of sex chromosomes at two distinct time points, or the reversion of a former Y chromosome to an autosome. [ABSTRACT FROM AUTHOR]

Archaeogenomic research has proven to be a valuable tool to trace migrations of historic and prehistoric individuals and groups, whereas relationships within a group or burial site have not been investigated to a large extent. Knowing the genetic kinship of historic and prehistoric individuals would give important insights into social structures of ancient and historic cultures. Most archaeogenetic research concerning kinship has been restricted to uniparental markers, while studies using genome-wide information were mainly focused on comparisons between populations. Applications which infer the degree of relationship based on modern-day DNA information typically require diploid genotype data. Low concentration of endogenous DNA, fragmentation and other post-mortem damage to ancient DNA (aDNA) makes the application of such tools unfeasible for most archaeological samples. To infer family relationships for degraded samples, we developed the software READ (Relationship Estimation from Ancient DNA). We show that our heuristic approach can successfully infer up to second degree relationships with as little as 0.1x shotgun coverage per genome for pairs of individuals. We uncover previously unknown relationships among prehistoric individuals by applying READ to published aDNA data from several human remains excavated from different cultural contexts. In particular, we find a group of five closely related males from the same Corded Ware culture site in modern-day Germany, suggesting patrilocality, which highlights the possibility to uncover social structures of ancient populations by applying READ to genome-wide aDNA data. READ is publicly available from . [ABSTRACT FROM AUTHOR]

Men have a higher rate of completed suicide than women, which suggests that sex chromosome abnormalities may be related to the pathophysiology of suicide. Recent studies have found an aberrant loss of chromosome Y (LOY) in various diseases; however, no study has investigated whether there is an association between LOY and suicide. The purpose of this study was to determine whether LOY occurs in men who completed suicide. Our study consisted of 286 male Japanese subjects comprised of 140 suicide completers without severe physical illness (130 post-mortem samples of peripheral blood and 10 brains) and 146 age-matched control subjects (130 peripheral blood samples from healthy individuals and 16 post-mortem brains). LOY was measured as the chromosome Y/chromosome X ratio of the fluorescent signal of co-amplified short sequences from the Y-X homologous amelogenin genes (AMELY and AMELX). Regression analyses showed that LOY in the blood of suicide completers was significantly more frequent than that found in controls (odds ratio = 3.50, 95% confidence interval = 1.21–10.10), but not in the dorsolateral prefrontal cortex (DLPFC) region of brain. Normal age-dependent LOY in blood was found in healthy controls (r = -0.353, p < 0.001), which was not seen in suicide completers (r = -0.119, p = 0.177). DLPFC tissue had age-dependent LOY (B = -0.002, p = 0.015), which was independent of phenotype. To our knowledge, this is the first study demonstrating that LOY in blood is associated with suicide completion. In addition, our findings are the first to also indicate that age-dependent LOY may occur not only in blood, but also in specific brain regions. [ABSTRACT FROM AUTHOR]

The human Y-chromosome does not recombine across its male-specific part and is therefore an excellent marker of human migrations. It also plays an important role in male fertility. However, its evolution is difficult to fully understand because of repetitive sequences, inverted repeats and the potentially large role of gene conversion. Here we perform an evolutionary analysis of 62 Y-chromosomes of Danish descent sequenced using a wide range of library insert sizes and high coverage, thus allowing large regions of these chromosomes to be well assembled. These include 17 father-son pairs, which we use to validate variation calling. Using a recent method that can integrate variants based on both mapping and de novo assembly, we genotype 10898 SNVs and 2903 indels (max length of 27241 bp) in our sample and show by father-son concordance and experimental validation that the non-recurrent SNP and indel variation on the Y chromosome tree is called very accurately. This includes variation called in a 0.9 Mb centromeric heterochromatic region, which is by far the most variable in the Y chromosome. Among the variation is also longer sequence-stretches not present in the reference genome but shared with the chimpanzee Y chromosome. We analyzed 2.7 Mb of large inverted repeats (palindromes) for variation patterns among the two palindrome arms and identified 603 mutation and 416 gene conversions events. We find clear evidence for GC-biased gene conversion in the palindromes (and a balancing AT mutation bias), but irrespective of this, also a strong bias towards gene conversion towards the ancestral state, suggesting that palindromic gene conversion may alleviate Muller’s ratchet. Finally, we also find a large number of large-scale gene duplications and deletions in the palindromic regions (at least 24) and find that such events can consist of complex combinations of simultaneous insertions and deletions of long stretches of the Y chromosome. [ABSTRACT FROM AUTHOR]

The Khon Mueang represent the major group of people present in today’s northern Thailand. While linguistic and genetic data seem to support a shared ancestry between Khon Mueang and other Tai-Kadai speaking people, the possibility of an admixed origin with contribution from local Mon-Khmer population could not be ruled out. Previous studies conducted on northern Thai people did not provide a definitive answer and, in addition, have largely overlooked the distribution of paternal lineages in the area. In this work we aim to provide a comprehensive analysis of Y paternal lineages in northern Thailand and to explicitly model the origin of the Khon Mueang population. We obtained and analysed new Y chromosomal haplogroup data from more than 500 northern Thai individuals including Khon Mueang, Mon-Khmer and Tai-Kadai. We also explicitly simulated different demographic scenarios, developed to explain the Khon Mueang origin, employing an ABC simulation framework on both mitochondrial and Y microsatellites data. Our results highlighted a similar haplogroup composition of Khon Mueang and Tai-Kadai populations in northern Thailand, with shared high frequencies of haplogroups O-PK4, O-M117 and O-M111. Our ABC simulations also favoured a model in which the ancestors of modern Khon Mueang originated recently after a split from the other Tai-Kadai populations. Our different analyses concluded that the ancestors of Khon Mueang are likely to have originated from the same source of the other Tai-Kadai groups in southern China, with subsequent admixture events involving native Mon-Khmer speakers restricted to some specific populations. [ABSTRACT FROM AUTHOR]

Triatoma infestans is the most important Chagas disease vector in South America. Two main evolutionary lineages, named Andean and non-Andean, have been recognized by geographical distribution, phenetic and genetic characteristics. One of the main differences is the genomic size, varying over 30% in their haploid DNA content. Here we realize a genome wide analysis to compare the repetitive genome fraction (repeatome) between both lineages in order to identify the main repetitive DNA changes occurred during T. infestans differentiation process. RepeatExplorer analysis using Illumina reads showed that both lineages exhibit the same amount of non-repeat sequences, and that satellite DNA is by far the major component of repetitive DNA and the main responsible for the genome size differentiation between both lineages. We characterize 42 satellite DNA families, which are virtually all present in both lineages but with different amount in each lineage. Furthermore, chromosomal location of satellite DNA by fluorescence in situ hybridization showed that genomic variations in T. infestans are mainly due to satellite DNA families located on the heterochromatic regions. The results also show that many satDNA families are located on the euchromatic regions of the chromosomes. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the genetic polymorphisms of 23 Y-STR loci from PowerPlex® Y23 system in 916 unrelated healthy male individuals from Chinese Jiangsu Han, and observed 912 different haplotypes including 908 unique haplotypes and 4 duplicate haplotypes. The haplotype diversity reached 0.99999 and the discrimination capacity and match probability were 0.9956 and 0.0011, respectively. The gene diversity values ranged from 0.3942 at DYS438 to 0.9607 at DYS385a/b. Population differentiation within 10 Jiangsu Han subpopulations were evaluated by RST values and visualized in Neighbor-Joining trees and Multi-Dimensional Scaling plots as well as population relationships between the Jiangsu Han population and other 18 Eastern Asian populations. Such results indicated that the 23 Y-STR loci were highly polymorphic in Jiangsu Han population and played crucial roles in forensic application as well as population genetics. For the first time, we reported the genetic diversity of male lineages in Jiangsu Han population at a high-resolution level of 23 Y-STR set and consequently contributed to familial searching, offender tracking, and anthropology analysis of Jiangsu Han population. [ABSTRACT FROM AUTHOR]

The Y-chromosomal TSPY gene is one of the highest copy number mammalian protein coding gene and represents a unique biological model to study various aspects of genomic copy number variations. This study investigated the age-related copy number variability of the bovine TSPY gene, a new and unstudied aspect of the biology of TSPY that has been shown to vary among cattle breeds, individual bulls and somatic tissues. The subjects of this prospective 30-month long study were 25 Holstein bulls, sampled every six months. Real-time quantitative PCR was used to determine the relative TSPY copy number (rTSPY CN) and telomere length in the DNA samples extracted from blood. Twenty bulls showed an altered rTSPY CN after 30 months, although only 9 bulls showed a significant change (4 significant increase while 5 significant decrease, P<0.01). The sequential sampling provided the flow of rTSPY CN over six observations in 30 months and wide-spread variation of rTSPY CN was detected. Although a clear trend of the direction of change was not identifiable, the highly dynamic changes of individual rTSPY CN in aging bulls were observed here for the first time. In summary we have observed a highly variable rTSPY CN in bulls over a short period of time. Our results suggest the importance of further long term studies of the dynamics of rTSPY CN variablility. [ABSTRACT FROM AUTHOR]

Austronesian diffusion is considered one of the greatest dispersals in human history; it led to the peopling of an extremely vast region, ranging from Madagascar in the Indian Ocean to Easter Island in Remote Oceania. The Y-chromosome haplogroup O3a2b*-P164(xM134), a predominant paternal lineage of Austronesian populations, is found at high frequencies in Polynesian populations. However, the internal phylogeny of this haplogroup remains poorly investigated. In this study, we analyzed -seventeen Y-chromosome sequences of haplogroup O3a2b*-P164(xM134) and generated a revised phylogenetic tree of this lineage based on 310 non-private Y-chromosome polymorphisms. We discovered that all available O3a2b*-P164(xM134) samples belong to the newly defined haplogroup O3a2b2-N6 and samples from Austronesian populations belong to the sublineage O3a2b2a2-F706. Additionally, we genotyped a series of Y-chromosome polymorphisms in a large collection of samples from China. We confirmed that the sublineage O3a2b2a2b-B451 is unique to Austronesian populations. We found that O3a2b2-N6 samples are widely distributed on the eastern coastal regions of Asia, from Korea to Vietnam. Furthermore, we propose- that the O3a2b2a2b-B451 lineage represents a genetic connection between ancestors of Austronesian populations and ancient populations in North China, where foxtail millet was domesticated about 11,000 years ago. The large number of newly defined Y-chromosome polymorphisms and the revised phylogenetic tree of O3a2b2-N6 will be helpful to explore the origin of proto-Austronesians and the early diffusion process of Austronesian populations. [ABSTRACT FROM AUTHOR]

We evaluated performance characteristics of a laboratory-developed, non-invasive prenatal screening (NIPS) assay for fetal aneuploidies. This assay employs massively parallel shotgun sequencing with full automation. GC sequencing bias correction and statistical smoothing were performed to enhance discrimination of affected and unaffected pregnancies. Maternal plasma samples from pregnancies with known aneuploidy status were used for assay development, verification, and validation. Assay verification studies using 2,085 known samples (1873 unaffected, 69 trisomy 21, 20 trisomy 18, 17 trisomy 13) demonstrated complete discrimination between autosomal trisomy (Z scores >8) and unaffected (Z scores <4) singleton pregnancies. A validation study using 552 known samples (21 trisomy 21, 10 trisomy 18, 1 trisomy 13) confirmed complete discrimination. Twin pregnancies showed similar results. Follow-up of abnormal results from the first 10,000 clinical samples demonstrated PPVs of 98% (41/42) for trisomy 21, 92% (23/25) for trisomy 18, and 69% (9/13) for trisomy 13. Adjustment for causes of false-positive results identified during clinical testing (eg, maternal duplications) improved PPVs to 100% for trisomy 21 and 96% for trisomy 18. This NIPS test demonstrates excellent discrimination between trisomic and unaffected pregnancies. The PPVs obtained in initial clinical testing are substantially higher than previously reported NIPS methods. [ABSTRACT FROM AUTHOR]

The mammalian Y chromosome plays a critical role in spermatogenesis. However, the exact functions of each gene in the Y chromosome have not been completely elucidated, partly owing to difficulties in gene targeting analysis of the Y chromosome. Zfy was first proposed to be a sex determination factor, but its function in spermatogenesis has been recently elucidated. Nevertheless, Zfy gene targeting analysis has not been performed thus far. Here, we adopted the highly efficient CRISPR/Cas9 system to generate individual Zfy1 or Zfy2 knockout (KO) mice and Zfy1 and Zfy2 double knockout (Zfy1/2-DKO) mice. While individual Zfy1 or Zfy2-KO mice did not show any significant phenotypic alterations in fertility, Zfy1/2-DKO mice were infertile and displayed abnormal sperm morphology, fertilization failure, and early embryonic development failure. Mass spectrometric screening, followed by confirmation with western blot analysis, showed that PLCZ1, PLCD4, PRSS21, and HTT protein expression were significantly deceased in spermatozoa of Zfy1/2-DKO mice compared with those of wild-type mice. These results are consistent with the phenotypic changes seen in the double-mutant mice. Collectively, our strategy and findings revealed that Zfy1 and Zfy2 have redundant functions in spermatogenesis, facilitating a better understanding of fertilization failure and early embryonic development failure. [ABSTRACT FROM AUTHOR]

Sex determination is important in archeology and anthropology for the study of past societies, cultures, and human activities. Sex determination is also one of the most important components of individual identification in criminal investigations. We developed a new method of sex determination by detecting a single-nucleotide polymorphism in the amelogenin gene using amplified product-length polymorphisms in combination with sex-determining region Y analysis. We particularly focused on the most common types of postmortem DNA damage in ancient and forensic samples: fragmentation and nucleotide modification resulting from deamination. Amplicon size was designed to be less than 60 bp to make the method more useful for analyzing degraded DNA samples. All DNA samples collected from eight Japanese individuals (four male, four female) were evaluated correctly using our method. The detection limit for accurate sex determination was determined to be 20 pg of DNA. We compared our new method with commercial short tandem repeat analysis kits using DNA samples artificially fragmented by ultraviolet irradiation. Our novel method was the most robust for highly fragmented DNA samples. To deal with allelic dropout resulting from deamination, we adopted “bidirectional analysis,” which analyzed samples from both sense and antisense strands. This new method was applied to 14 Jomon individuals (3500-year-old bone samples) whose sex had been identified morphologically. We could correctly identify the sex of 11 out of 14 individuals. These results show that our method is reliable for the sex determination of highly degenerated samples. [ABSTRACT FROM AUTHOR]

Condensed Y chromosomes in Rumex acetosa L. root-tip nuclei were studied using 5-azaC treatment and immunohistochemical detection of methylated histones. Although Y chromosomes were decondensed within root meristem in vivo, they became condensed and heteropycnotic in roots cultured in vitro. 5-azacytidine (5-azaC) treatment of cultured roots caused transitional dispersion of their Y chromosome bodies, but 7 days after removal of the drug from the culture medium, Y heterochromatin recondensed and again became visible. The response of Rumex sex chromatin to 5-azaC was compared with that of condensed segments of pericentromeric heterochromatin in Rhoeo spathacea (Sw.) Stearn roots. It was shown that Rhoeo chromocentres, composed of AT-rich constitutive heterochromatin, did not undergo decondensation after 5-azaC treatment. The Y-bodies observed within male nuclei of R. acetosa were globally enriched with H3 histone, demethylated at lysine 4 and methylated at lysine 9. This is the first report of histone tail-modification in condensed sex chromatin in plants. Our results suggest that the interphase condensation of Y chromosomes in Rumex is facultative rather than constitutive. Furthermore, the observed response of Y-bodies to 5-azaC may result indirectly from demethylation and the subsequent altered expression of unknown genes controlling tissue-specific Y-inactivation as opposed to the global demethylation of Y-chromosome DNA.

Rapidly Mutating Y-STRs (RM Y-STRs) were recently introduced in forensics in order to increase the differentiation of Y-chromosomal profiles even in case of close relatives. We estimate RM Y-STRs mutation rates and their power to discriminate between related individuals by using samples extracted from a wide set of paternal pedigrees and by comparing RM Y-STRs results with those obtained from the Y-filer set. In addition, we tested the ability of RM Y-STRs to discriminate between unrelated individuals carrying the same Y-filer haplotype, using the haplogroup R-M269 (reportedly characterised by a strong resemblance in Y-STR profiles) as a case study. Our results, despite confirming the high mutability of RM Y-STRs, show significantly lower mutation rates than reference germline ones. Consequently, their power to discriminate between related individuals, despite being higher than the one of Y-filer, does not seem to improve significantly the performance of the latter. On the contrary, when considering R-M269 unrelated individuals, RM Y-STRs reveal significant discriminatory power and retain some phylogenetic signal, allowing the correct classification of individuals for some R-M269-derived sub-lineages. These results have important implications not only for forensics, but also for molecular anthropology, suggesting that RM Y-STRs are useful tools for exploring subtle genetic variability within Y-chromosomal haplogroups. [ABSTRACT FROM AUTHOR]

Due to its palindromic setup, AZFc (Azoospermia Factor c) region of chromosome Y is one of the most unstable regions of the human genome. It contains eight gene families expressed mainly in the testes. Several types of rearrangement resulting in changes in the cumulative copy number of the gene families were reported to be associated with diseases such as male infertility and testicular germ cell tumors. The best studied AZFc rearrangement is gr/gr deletion. Its carriers show widespread phenotypic variation from azoospermia to normospermia. This phenomenon was initially attributed to different gr/gr subtypes that would eliminate distinct members of the affected gene families. However, studies conducted to confirm this hypothesis have brought controversial results, perhaps, in part, due to the shortcomings of the utilized subtyping methodology. This proof-of-concept paper is meant to introduce here a novel method aimed at subtyping AZFc rearrangements. It is able to differentiate the partial deletion and partial duplication subtypes of the Deleted in Azoospermia (DAZ) gene family. The keystone of the method is the determination of the copy number of the gene family member-specific variant(s) in a series of sequence family variant (SFV) positions. Most importantly, we present a novel approach for the correct interpretation of the variant copy number data to determine the copy number of the individual DAZ family members in the context of frequent interloci gene conversion.Besides DAZ1/DAZ2 and DAZ3/DAZ4 deletions, not yet described rearrangements such as DAZ2/DAZ4 deletion and three duplication subtypes were also found by the utilization of the novel approach. A striking feature is the extremely high concordance among the individual data pointing to a certain type of rearrangement. In addition to being able to identify DAZ deletion subtypes more reliably than the methods used previously, this approach is the first that can discriminate DAZ duplication subtypes as well. [ABSTRACT FROM AUTHOR]

In the past decades ancient DNA research has brought numerous insights to archaeological research where traditional approaches were limited. The determination of sex in human skeletal remains is often challenging for physical anthropologists when dealing with incomplete, juvenile or pathological specimens. Molecular approaches allow sexing on the basis of sex-specific markers or by calculating the ratio of DNA derived from different chromosomes. Here we propose a novel approach that relies on the ratio of X chromosome-derived shotgun sequencing data to the autosomal coverage, thus establishing the probability of an XX or XY karyotype. Applying this approach to the individuals of the Upper Paleolithic triple burial of Dolní Věstonice reveals that all three skeletons, including the individual DV 15, whose sex has long been debated due to a pathological condition, were male. [ABSTRACT FROM AUTHOR]

Background: With the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it affects the accuracy of NIPT-based sequencing for fetal trisomies 21, 18 and 13. Several approaches have been developed to calculate the cffDNA fraction of the total cell-free DNA in the maternal plasma. However, most approaches depend on specific single nucleotide polymorphism (SNP) allele information or are restricted to male fetuses. Methods: In this study, we present an innovative method to accurately deduce the concentration of the cffDNA fraction using only maternal plasma DNA. SNPs were classified into four maternal-fetal genotype combinations and three boundaries were added to capture effective SNP loci in which the mother was homozygous and the fetus was heterozygous. The median value of the concentration of the fetal DNA fraction was estimated using the effective SNPs. A depth-bias correction was performed using simulated data and corresponding regression equations for adjustments when the depth of the sequencing data was below 100-fold or the cffDNA fraction is less than 10%. Results: Using our approach, the median of the relative bias was 0.4% in 18 maternal plasma samples with a median sequencing depth of 125-fold. There was a significant association (r = 0.935) between our estimations and the estimations inferred from the Y chromosome. Furthermore, this approach could precisely estimate a cffDNA fraction as low as 3%, using only maternal plasma DNA at the targeted region with a sequencing depth of 65-fold. We also used PCR instead of parallel sequencing to calculate the cffDNA fraction. There was a significant association (r = 98.2%) between our estimations and those inferred from the Y chromosome. [ABSTRACT FROM AUTHOR]

RNA-Sequencing (RNA-Seq) provides valuable information for characterizing the molecular nature of the cells, in particular, identification of differentially expressed transcripts on a genome-wide scale. Unfortunately, cost and limited specimen availability often lead to studies with small sample sizes, and hypothesis testing on differential expression between classes with a small number of samples is generally limited. The problem is especially challenging when only one sample per each class exists. In this case, only a few methods among many that have been developed are applicable for identifying differentially expressed transcripts. Thus, the aim of this study was to develop a method able to accurately test differential expression with a limited number of samples, in particular non-replicated samples. We propose a local-pooled-error method for RNA-Seq data (LPEseq) to account for non-replicated samples in the analysis of differential expression. Our LPEseq method extends the existing LPE method, which was proposed for microarray data, to allow examination of non-replicated RNA-Seq experiments. We demonstrated the validity of the LPEseq method using both real and simulated datasets. By comparing the results obtained using the LPEseq method with those obtained from other methods, we found that the LPEseq method outperformed the others for non-replicated datasets, and showed a similar performance with replicated samples; LPEseq consistently showed high true discovery rate while not increasing the rate of false positives regardless of the number of samples. Our proposed LPEseq method can be effectively used to conduct differential expression analysis as a preliminary design step or for investigation of a rare specimen, for which a limited number of samples is available. [ABSTRACT FROM AUTHOR]

Background: X&Y chromosomal aneuploidies are among the most common human whole-chromosomal copy number changes, but the population-based incidence and prevalence in the child-bearing population is unclear. Methods: This retrospective analysis of prospectively collected data leveraged a routine non-invasive prenatal test (NIPT) using parental genotyping to estimate the population-based incidence of X&Y chromosome variations in this population referred for NIPT (generally due to advanced maternal age). Results: From 141,916 women and 29,336 men, 119 X&Y chromosomal abnormalities (prevalence: 1 in 1,439) were identified. Maternal findings include: 43 cases of 45,X (40 mosaic); 30 cases of 47,XXX (12 mosaic); 3 cases of 46,XX uniparental disomy; 2 cases of 46,XY/46,XX; 23 cases of mosaicism of unknown type; 2 cases of 47,XX,i(X)(q10). Paternal findings include: 2 cases of 47,XXY (1 mosaic); 10 cases of 47,XYY (1 mosaic); 4 partial Y deletions. Conclusions: Single chromosome aneuploidy was present in one of every 1,439 individuals considered in this study, showing 47,XXX; 47,XX,i(X)(q10); 47,XYY; 47,XXY, partial Y deletions, and a high level of mosaicism for 45,X. This expands significantly our understanding of X&Y chromosomal variations and fertility issues, and is critical for families and adults affected by these disorders. This current and extensive information on fertility will be beneficial for genetic counseling on prenatal diagnoses as well as for newly diagnosed postnatal cases. [ABSTRACT FROM AUTHOR]

Unmapped next-generation sequencing reads are typically ignored while they contain biologically relevant information. We systematically analyzed unmapped reads from whole genome sequencing of 33 inbred rat strains. High quality reads were selected and enriched for biologically relevant sequences; similarity-based analysis revealed clustering similar to previously reported phylogenetic trees. Our results demonstrate that on average 20% of all unmapped reads harbor sequences that can be used to improve reference genomes and generate hypotheses on potential genotype-phenotype relationships. Analysis pipelines would benefit from incorporating the described methods and reference genomes would benefit from inclusion of the genomic segments obtained through these efforts. [ABSTRACT FROM AUTHOR]

Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing. [ABSTRACT FROM AUTHOR]

The evolutionary history of macaques, genus Macaca, has been under debate due to the short times of divergence. In this study, maternal, paternal, and biparental genetic systems were applied to infer phylogenetic relationships among macaques and to trace ancient hybridization events in their evolutionary history. Using a PCR display method, 17 newly phylogenetically informative Alu insertions were identified from M. assamensis. We combined presence/absence analysis of 84 Alu elements with mitochondrial genomes as well as nuclear sequences (five autosomal genes, two Y chromosomal genes, and one X chromosomal fragment) to reconstruct a robust macaque phylogeny. Topologies generated from different inherited markers were similar supporting six well defined species groups and a close relationship of M. assamensis and M. thibetana, but differed in the placing of M. arctoides. Both Alu elements and nuclear genes supported that M. arctoides was close to the sinica group, whereas the mitochondrial data clustered it into the fascicularis/mulatta lineage. Our results reveal that a sex-biased hybridization most likely occurred in the evolutionary history of M. arctoides, and suggest an introgressive pattern of male-mediated gene flow from the ancestors of M. arctoides to the M. mulatta population followed by nuclear swamping. According to the estimation of divergence dates, the hybridization occurred around 0.88~1.77 mya (nuclear data) or 1.38~2.56 mya (mitochondrial data). In general, our study indicates that a combination of various molecular markers could help explain complicated evolutionary relationships. Our results have provided new insights into the evolutionary history of macaques and emphasize that hybridization might play an important role in macaque evolution. [ABSTRACT FROM AUTHOR]

The non-recombining nature of the Y chromosome and the well-established phylogeny of Y-specific Single Nucleotide Polymorphisms (Y-SNPs) make them useful for defining haplogroups with high geographical specificity; therefore, they are more apt than the Y-STRs to detect population stratification in admixed populations from diverse continental origins. Different Y-SNP typing strategies have been described to address issues of population history and movements within geographic territories of interest. In this study, we investigated a set of 41 Y-SNPs in 1217 unrelated males from the five Brazilian geopolitical regions, aiming to disclose the genetic structure of male lineages in the country. A population comparison based on pairwise FST genetic distances did not reveal statistically significant differences in haplogroup frequency distributions among populations from the different regions. The genetic differences observed among regions were, however, consistent with the colonization history of the country. The sample from the Northern region presented the highest Native American ancestry (8.4%), whereas the more pronounced African contribution could be observed in the Northeastern population (15.1%). The Central-Western and Southern samples showed the higher European contributions (95.7% and 93.6%, respectively). The Southeastern region presented significant European (86.1%) and African (12.0%) contributions. The subtyping of the most frequent European lineage in Brazil (R1b1a-M269) allowed differences in the genetic European background of the five Brazilian regions to be investigated for the first time. [ABSTRACT FROM AUTHOR]

We show that the geophilomorph centipede Strigamia maritima possesses an XX/XY system of sex chromosomes, with males being the heterogametic sex. This is, to our knowledge, the first report of sex chromosomes in any geophilomorph centipede. Using the recently assembled Strigamia genome sequence, we identified a set of scaffolds differentially represented in male and female DNA sequence. Using quantitative real-time PCR, we confirmed that three candidate X chromosome-derived scaffolds are present at approximately twice the copy number in females as in males. Furthermore, we confirmed that six candidate Y chromosome-derived scaffolds contain male-specific sequences. Finally, using this molecular information, we designed an X chromosome-specific DNA probe and performed fluorescent in situ hybridization against mitotic and meiotic chromosome spreads to identify the Strigamia XY sex-chromosome pair cytologically. We found that the X and Y chromosomes are recognizably different in size during the early pachytene stage of meiosis, and exhibit incomplete and delayed pairing. [ABSTRACT FROM AUTHOR]

The European black fly Simulium (Simulium) colombaschense (Scopoli), once responsible for as many as 22,000 livestock deaths per year, is chromosomally mapped, permitting its evolutionary relationships and pest drivers to be inferred. The species is 12 fixed inversions removed from the standard sequence of the subgenus Simulium. Three of these fixed inversions, 38 autosomal polymorphisms, and a complex set of 12 X and 6 Y chromosomes in 29 zygotic combinations uniquely characterize S. colombaschense and reveal 5 cytoforms: ‘A’ in the Danube watershed, ‘B’ in Italy’s Adige River, ‘C’ in the Aliakmonas River of Greece, ‘D’ in the Aoös drainage in Greece, and ‘E’ in the Belá River of Slovakia. ‘C’ and ‘D’ are reproductively isolated from one another, and ‘B’ is considered a cytotype of ‘A,’ the probable name bearer of colombaschense. The species status of ‘E’ cannot be determined without additional collections. Three derived polytene sequences, based on outgroup comparisons, place S. colombaschense in a clade of species composed of the S. jenningsi, S. malyschevi, and S. reptans species groups. Only cytoforms ‘A’ and ‘B’ are pests. Within the Simuliidae, pest status is reached through one of two principal pathways, both of which promote the production of large populations of blood-seeking flies: (1) colonization of the world’s largest rivers (habitat specialization) or (2) colonization of multiple habitat types (habitat generalization). Evolutionary acquisition of the ability to colonize large rivers by an ancestor of the S. jenningsi-malyschevi-reptans clade set the scene for the pest status of S. colombaschense and other big-river members of the clade. In an ironic twist, the macrogenome of S. colombaschense reveals that the name associated with history’s worst simuliid pest represents a complex of species, two or more of which are nonpests potentially vulnerable to loss of their limited habitat. [ABSTRACT FROM AUTHOR]

Fetal cells enter maternal circulation during pregnancy and persist in the woman’s body for decades, achieving a form of physiological microchimerism. These cells were also evidenced in tumors. We investigated the frequency and concentration of fetal microchimerism in the local breast cancer environment. From 19 patients with confirmed breast neoplasia, after breast surgical resection, we collected three fresh specimens from the tumor core, breast tissue at tumor periphery, and adjacent normal breast tissue. The presence of male DNA was analyzed with a quantitative PCR assay for the sex determining region gene (SRY) gene. In the group of women who had given birth to at least one son, we detected fetal microchimerism in 100% of samples from tumors and their periphery and in 64% (9 of 14) of those from normal breast tissue. The tissues from the tumor and its periphery carry a significantly increased number of SRY copies compared to its neighboring common breast tissue (p = 0.005). The median of the normalized SRY-signal was about 77 (range, 3.2–21467) and 14-fold (range, 1.3–2690) greater in the tumor and respectively in the periphery than in the normal breast tissue. In addition, the relative expression of the SRY gene had a median 5.5 times larger in the tumor than in its periphery (range, 1.1–389.4). We found a heterogeneous distribution of fetal microchimerism in breast cancer environment. In women with sons, breast neoplasia harbors male cells at significantly higher levels than in peripheral and normal breast tissue. [ABSTRACT FROM AUTHOR]

Because male gene flow cannot easily be estimated directly in many organisms, Hedrick et al. (2013) provided an approach to estimate male gene flow given estimates of diploid nuclear and female differentiation. This approach appears to work well when there is lower female than male gene flow. However, in a tiger data set there was less female differentiation observed as estimated by mitochondrial DNA than expected given the observed overall nuclear diploid differentiation. To analyze these data, we suggest an alternative approach which allows incorporation of sex-specific gene flow and sex-specific effective population size. We find that the pattern of differentiation observed in tigers was consistent with a lower male than female effective population size using this alternative approach. Further, this finding is consistent with observed data in tigers where the male effective population size was 33% that of the female effective population size. [ABSTRACT FROM AUTHOR]