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With the recent and unprecedented progress in retrieving DNA sequence information from a large number of individuals of any species, conservation genetic research has entered a new phase. Specifically, it has become possible to study how genomes of endangered species respond to reductions in population size. Using genomic and bioinformatic approaches, in this thesis I investigate the contemporary Scandinavian wolf population founded 40 years ago by only three individuals, after the original population had been extirpated some decades earlier. The origin of the founders has been the subject of controversy, so I aimed to trace their origin using first male-specific Y chromosome sequences, and then whole-genome sequence data. I compared Scandinavian wolves to wolves from the nearby Finnish-Russian population as well as to publicly available wolf and dog samples from around the northern hemisphere, and found that the Scandinavian founders shared Y-haplotypes only with Finnish wolves. Consistent with this observation, when assessing population structure on the genomic scale, founders clustered with Finnish and Russian wolves, and an admixture analysis showed no other ancestries, nor traces of introgression from dogs. Small populations tend to have less genetic variation than larger populations, which might reduce their adaptive potential and increase the risk for extinction. A common measure used to investigate the genetic health of small populations is the genetic load, which is the fitness reduction of individuals due to accumulation of deleterious variants. I assessed the genetic load in Scandinavian wolves, divided into the components masked load (comprised of deleterious mutations in heterozygous state) and realized load (comprised of deleterious mutations in homozygous state), using both putatively deleterious single nucleotides and structural variants. I found that the realized load increased with every generation of inbreeding but was alleviated after genetic re

In 2021, we published the results of genomic analyses carried out on the famous bishop of Lund, Peder Winstrup, and the mummified remains of a 5–6-month-old fetus discovered in the same burial. We concluded that the two individuals were second-degree relatives and explored the genealogy of Peder Winstrup to further understand the possible relation between them. Through this analysis, we found that the boy was most probably Winstrup’s grandson and that the two were equally likely related either through Winstrup’s son, Peder, or his daughter, Anna Maria von Böhnen. To further resolve the specific kinship relation, we generated more genomic data from both Winstrup and the boy and implemented more recently published analytical tools in detailed Y chromosome- and X chromosome-based kinship analyses to distinguish between the competing hypotheses regarding maternal and paternal relatedness. We found that the individuals’ Y chromosome lineages belonged to different sub-lineages and that the X-chromosomal kinship coefficient calculated between the two individuals were elevated, suggesting a grandparent–grandchild relation through a female, i.e., Anna Maria von Böhnen. Finally, we also performed metagenomic analyses, which did not identify any pathogens that could be unambiguously associated with the fatalities.

Y chromosomal ampliconic genes (YAGs) are important for male fertility, as they encode proteins functioning in spermatogenesis. The variation in copy number and expression levels of these multicopy gene families has been studied in great apes; however, the diversity of splicing variants remains unexplored. Here, we deciphered the sequences of polyadenylated transcripts of all nine YAG families (BPY2, CDY, DAZ, HSFY, PRY, RBMY, TSPY, VCY, and XKRY) from testis samples of six great ape species (human, chimpanzee, bonobo, gorilla, Bornean orangutan, and Sumatran orangutan). To achieve this, we enriched YAG transcripts with capture probe hybridization and sequenced them with long (Pacific Biosciences) reads. Our analysis of this data set resulted in several findings. First, we observed evolutionarily conserved alternative splicing patterns for most YAG families except for BPY2 and PRY. Second, our results suggest that BPY2 transcripts and proteins originate from separate genomic regions in bonobo versus human, which is possibly facilitated by acquiring new promoters. Third, our analysis indicates that the PRY gene family, having the highest representation of noncoding transcripts, has been undergoing pseudogenization. Fourth, we have not detected signatures of selection in the five YAG families shared among great apes, even though we identified many species-specific protein-coding transcripts. Fifth, we predicted consensus disorder regions across most gene families and species, which could be used for future investigations of male infertility. Overall, our work illuminates the YAG isoform landscape and provides a genomic resource for future functional studies focusing on infertility phenotypes in humans and critically endangered great apes.

Deletion of the azoospermia factor c (AZFc), located on the long arm of the Y chromosome, is a cause of male infertility. The structure of the Y chromosome is diversified by the copy number of various genes, such as deleted in azoospermia (DAZ), basic protein Y2, chromodomain Y1, testis-specific transcript Y-linked 4, and Golgi autoantigen golgin subfamily a2 like Y, located in the AZF region. In this study, we investigated the deletion of each gene copy and analyzed its relationship with Japanese male infertility. Deletions of single nucleotide variants of each gene copy in 721 proven fertile men as controls, 139 patients with non-obstructive azoospermia (NOA), and 56 patients with oligozoospermia (OS) were analyzed via polymerase chain reaction-restriction fragment length polymorphism analysis. Their association with infertility was analyzed using logistic regression analysis adjusted for the Y-chromosome haplogroup, D1a2a. Deletions of DAZ/II in the r1 region and DAZ/V in the r1 and r2 regions showed significant associations with NOA (odds ratio [OR] = 4.15, 95% confidence interval [CI] = 1.18–14.6, P = 0.026; OR = 4.19, 95% CI = 1.19–14.7, P = 0.025, respectively). They did not show any association with OS. Partial deletion of the AZFc region affects spermatogenesis in Japanese male.

Island Southeast Asia (ISEA) and Oceania host one of the world's richest assemblages of human phenotypic, linguistic, and cultural diversity. Despite this, the region's male genetic lineages are globally among the last to remain unresolved. We compiled similar to 9.7 Mb of Y chromosome (chrY) sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this data set allows us to fully resolve and date the regional chrY phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region's initial settlement similar to 50 kya, and extensive expansions <6 kya. Notably, similar to 40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in ISEA, New Guinea, and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying similar to 25 kya, at the time of the last glacial maximum. This improved chrY topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and ISEA, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the chrY presented here thus enables a detailed exploration of past isolation, interaction, and change in one of the world's least understood regions.

Y Chromosomes of many species are gene poor and show low levels of nucleotide variation, yet they often display high amounts of structural diversity. Dobzhansky cataloged several morphologically distinct Y Chromosomes in Drosophila pseudoobscura that differ in size and shape, but the molecular causes of their large size differences are unclear. Here we use cytogenetics and long-read sequencing to study the sequence content of polymorphic Y Chromosomes in D. pseudoobscura We show that Y Chromosomes differ almost twofold in size, ranging from 30 to 60 Mb. Most of this size difference is caused by a handful of active transposable elements (TEs) that have recently expanded on the largest Y Chromosome, with different elements being responsible for Y expansion on differently sized D. pseudoobscura Y's. We show that Y Chromosomes differ in their heterochromatin enrichment and expression of Y-enriched TEs, and also influence expression of dozens of autosomal and X-linked genes. The same helitron element that showed the most drastic amplification on the largest Y in D. pseudoobscura independently amplified on a polymorphic large Y Chromosome in Drosophila affinis, suggesting that some TEs are inherently more prone to become deregulated on Y Chromosomes.

The Y chromosome is a valuable genetic marker for studying the origin and influence of paternal lineages in populations. In this study, we conducted Y-chromosomal lineage-tracing in Arabian horses. First, we resolved a Y haplotype phylogeny based on the next generation sequencing data of 157 males from several breeds. Y-chromosomal haplotypes specific for Arabian horses were inferred by genotyping a collection of 145 males representing most Arabian sire lines that are active around the globe. These lines formed three discrete haplogroups, and the same haplogroups were detected in Arabian populations native to the Middle East. The Arabian haplotypes were clearly distinct from the ones detected in Akhal Tekes, Turkoman horses, and the progeny of two Thoroughbred foundation sires. However, a haplotype introduced into the English Thoroughbred by the stallion Byerley Turk (1680), was shared among Arabians, Turkomans, and Akhal Tekes, which opens a discussion about the historic connections between Oriental horse types. Furthermore, we genetically traced Arabian sire line breeding in the Western World over the past 200 years. This confirmed a strong selection for relatively few male lineages and uncovered incongruences to written pedigree records. Overall, we demonstrate how fine-scaled Y-analysis contributes to a better understanding of the historical development of horse breeds., Peer Reviewed

The current territory of Trujillo, a coastal city in northern Peru, was occupied by various pre-Columbian cultures throughout history. With the arrival of European conquerors in the 16th century, started a process of admixture that continues to this day. The goals of this article are to identify and characterize autochthonous and allochthonous Y chromosome lineages in the population of Trujillo, and to compare its settlement processes with those seen in Argentinian populations. We analyzed paternal lineages by focusing on the non-recombinant region of the Y chromosome. An allele-specific amplification method was used to identify biallelic markers (SNPs) that determine autochthonous and allochthonous haplogroups for America, in multiplex PCR-AFLP reactions. As expected, this population showed a predominantly native ancestry, with high influence of European lineages., O atual território de Trujillo, uma cidade costeira no norte do Peru, foi povoado por várias culturas pré-colombianas ao longo da história. Com a chegada dos conquistadores europeus no século XVI, iniciou-se um processo de miscigenação que continua até hoje. Os objetivos deste trabalho são identificar e caracterizar as linhagens autóctones e alóctones do cromossomo Y na população de Trujillo para compreender os fenômenos populacionais e possíveis semelhanças entre a população estudada e as populações da Argentina. As linhagens parentais foram analisadas através da região não recombinante do cromossomo Y, empregando um método de amplificação alelo-específico para a identificação de marcadores bialélicos (SNPs) que determinam haplogrupos autóctones e alóctones para a América em reações PCR-AFLP multiplex. Segundo o esperado, essa população apresentou ascendência predominantemente nativa, com alta influência das linhagens européias., El actual territorio de Trujillo, una ciudad costera en el Norte de Perú, fue ocupado por diversas culturas precolombinas a lo largo de la historia. Con la llegada de los conquistadores europeos en el siglo XVI, se inició un proceso de mestizaje que continúa hasta la actualidad. Los objetivos de este trabajo son identificar y caracterizar linajes autóctonos y alóctonos del cromosoma Y en la población de Trujillo y evidenciar fenómenos del poblamiento y similitudes entre la población en estudio y poblaciones de Argentina. Se analizaron los linajes paternos a través de la región no recombinante del cromosoma Y por medio de un método de amplificación alelo-específica para la identificación marcadores bialélicos (SNPs) que determinan haplogrupos autóctonos y alóctonos para América en reacciones PCR-AFLP multiplex. Tal como se esperaba, esta población presentó una ancestralidad predominantemente nativa, con una alta influencia de linajes europeos.

Kako se Y hromozom kroz generacije ne menja rekombinacijama, prenosi se uglavnom nepromenjen sa oca na sina. Haplotipovi dobijeni kombinovanom analizom kratkih tandemskih ponovaka na Y hromozomu imaju široku primenu u forenzičkim analizama za definisanje paternalne linije muškog donora biološkog traga, posebno u slučajevima gde standardna analiza autozomnih markera nije dovoljno informativna. Y vezani haplotipovi se koriste i u evolucionim i genealoškim studijama, ali se za rekonstrukciju filogenije Y hromozoma koristi analiza polimorfizama pojedinačnih nukleotida. Promene na Y hromozomu se ipak dešavaju usled mutacija što može da dovede do diferencijacije Y vezanih haplotipova između oca i sinova. Tako mutacije u lokusima sa kratkim tandemskim ponovcima mogu da omoguće identifikaciju muškarca u okviru jedne paternalne linije, ali mogu i da dovedu do progrešnog isključenja biološkog srodstva. Usled toga je za tačnu interpretaciju genetičkih profila neophodna precizna procena stope mutacije pojedinačnih lokusa, za šta se koriste studije parova otac-sin ili velikih porodični stabala., Y chromosome is transmitted mostly unchanged from father to son due to the absence of recombination events. Haplotypes composed of Y-chromosomal short tandem repeat polymorphisms are widely used to define paternal line of unknown male perpetrator in forensic analysis, especially when standard analysis of autosomal markers is not informative enough. Y-chromosomal haplotypes are also used in evolutionary and genealogical studies, but single nucleotide polymorphisms are more suitable for the reconstruction of the Y chromosome phylogeny. However, Y chromosome changes due to mutations, which could lead to differentiation of Y haplotypes between father and sons. Thus, mutations in short tandem repeats loci can enable the identification of a man within a single paternal line, but they could also lead to an erroneous exclusion of biological paternity. Reliable mutation rates, for the proper use and accurate interpretation of genetic profiles, could be estimated from multi-generation pedigrees or father-son pairs.

For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells/individuals from the zygote throughout life. Here we will review and discuss relevant data showing how particular X- and Y-linked genes and epigenetic mechanisms controlling their expression and inheritance are involved, along with or independently of gonadal hormones, in the generation of sex differences in the brain.

Y haplogroups, defined by Y-SNPs, allow the reconstruction of the human Y chromosome genealogy. Recently, MPS based panels were introduced in the forensic genetics community for Y-SNP typing and identification of a broad range of haplogroups. The panels are based on an amplicon strategy and allow the detection of up to 15,600 Y-SNPs. The panels target up to 210,000 bps, which should be compared to the overall 8.9 Mbps comprising the unique regions of the non-recombining portion of the Y chromosome (NRY). We present an alternative approach of sequencing unique regions within the NRY using target enrichment probes and hybridization capture. A total of 359,954 probes were designed using the SureDesign software, representing 7.5 Mbps of the NRY. Library preparation and capture were performed using the Agilent SureSelect XT HS2 Target Enrichment method and sequencing was performed in a NovaSeq 6000 System. Besides individual barcodes, the method also included unique molecular barcodes for additional quality screening. The method was tested on admixed South Americans that carry a Y chromosome of haplogroup Q. We successfully identified novel variation that could potentially help refining haplogroup Q phylogeny.

BackgroundThe mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector's genome assembly. The existing assemblies of An. stephensi are draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution.ResultsTo access previously intractable genomic regions, we generated a reference-grade genome assembly and full transcript annotations that achieve a new standard for reference genomes of disease vectors. Here, we report novel species-specific transposable element (TE) families and insertions in functional genetic elements, demonstrating the widespread role of TEs in genome evolution and phenotypic variation. We discovered 29 previously hidden members of insecticide resistance genes, uncovering new candidate genetic elements for the widespread insecticide resistance observed in An. stephensi. We identified 2.4 Mb of the Y chromosome and seven new male-linked gene candidates, representing the most extensive coverage of the Y chromosome in any mosquito. By tracking full-length mRNA for > 15 days following blood feeding, we discover distinct roles of previously uncharacterized genes in blood metabolism and female reproduction. The Y-linked heterochromatin landscape reveals extensive accumulation of long-terminal repeat retrotransposons throughout the evolution and degeneration of this chromosome. Finally, we identify a novel Y-linked putative transcription factor that is expressed constitutively throughout male development and adulthood, suggesting an important role.ConclusionCollectively, these results and resources underscore the significance of previously hidden genomic elements in the biology of malaria mosquitoes and will accelerate the development of genetic control strategies of malaria transmission.

Throughout its distribution across Eurasia, domestic pig (Sus scrofa) populations have acquired differences through natural and artificial selection, and have often interbred. We resequenced 80 Eurasian pigs from nine different Asian and European breeds; we identify 42,288 reliable SNPs on the Y chromosome in a panel of 103 males, among which 96.1% are newly detected. Based on these new data, we elucidate the evolutionary history of pigs through the lens of the Y chromosome. We identify two highly divergent haplogroups: one present only in Asia and one fixed in Europe but present in some Asian populations. Analyzing the European haplotypes present in Asian populations, we find evidence of three independent waves of introgression from Europe to Asia in last 200 years, agreeing well with the literature and historical records. The diverse European lineages were brought in China by humans and left significant imprints not only on the autosomes but also on the Y chromosome of geographically and genetically distinct Chinese pig breeds. We also find a general excess of European ancestry on Y chromosomes relative to autosomes in Chinese pigs, an observation that cannot be explained solely by sex-biased migration and genetic drift. The European Y haplotype is associated with leaner meat production, and we hypothesize that the European Y chromosome increased in frequency in Chinese populations due to artificial selection. We find evidence of Y chromosomal gene flow between Sumatran wild boar and Chinese pigs. Our results demonstrate how human-mediated admixture and selection shaped the distribution of modern swine Y chromosomes.

Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30years to investigate the history of humans from a maternal and paternal perspective. Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture assays such as the 1240k, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield. Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the "mappable" regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240k capture, YMCA significantly improves the mean coverage and number of sites covered on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants. To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe.

CRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce genetic sexing systems, sex ratio distorters, or even sex-specific gene drives, for example. To explore this possibility, here we develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome. We functionally characterize the utility of this strain for both sex selection and gene drive finding it to be quite effective. To explore its utility for population control, we built mathematical models illustrating its dynamics as compared to other state-of-the-art systems designed for both population modification and suppression. Taken together, our results contribute to the development of current CRISPR genetic control tools and demonstrate the utility of using sex-linked Cas9 strains for genetic control of animals.

It has long been accepted that the Indigenous groups of Australia's Cape York Peninsula have numerous cultural traits that were adopted from people in New Guinea and/or the Torres Strait Islands after the formation of the Torres Strait around 8000 years ago. However, opinions differ on whether the movement of the traits in question was accompanied by gene flow events. Some argue for a significant amount of gene flow resulting from voyages from New Guinea and the Torres Strait Islands down the east coast of Cape York. Others contend that there was only contact at the northern end of the Cape and that the cultural traits spread through down-the-line transmission. In recent years partnerships between Australian institutions and Indigenous communities in Cape York have led to new genetic research that provides benefits to both parties. We review the currently available genetic data that have the potential to shed light on this issue, concluding that the data are inconsistent with significant gene flow between Indigenous Australians and Papuan people between 8000 years ago and the colonial period. There are indications of gene flow, but it most likely occurred in the Pleistocene rather than the Holocene. As such, the currently available genomic data do not support the hypothesis that the diffusion of cultural traits from New Guinea and/or the Torres Strait Islands into Cape York was accompanied by gene flow. The data suggest instead that the cultural traits most probably spread via down-the-line trade, exchange, and imitation. Our review highlights the gaps in the available genomic information from contemporary and ancestral descendants of Australia's first settlers, and we suggest that researchers adopt a more collaborative approach, involving Indigenous communities and their knowledge in project design, data collection, and dissemination, in future genomic studies in Australia.

The red fox (Vulpes vulpes) has a wide global distribution with many ecotypes and has been bred in captivity for various traits, making it a useful evolutionary model system. The Y chromosome represents one of the most informative markers of phylogeography, yet it has not been well-studied in the red fox due to a lack of the necessary genomic resources. We used a target capture approach to sequence a portion of the red fox Y chromosome in a geographically diverse red fox sample, along with other canid species, to develop single nucleotide polymorphism (SNP) markers, 13 of which we validated for use in subsequent studies. Phylogenetic analyses of the Y chromosome sequences, including calibration to outgroups, confirmed previous estimates of the timing of two intercontinental exchanges of red foxes, the initial colonization of North America from Eurasia approximately half a million years ago and a subsequent continental exchange before the last Pleistocene glaciation (~100,000 years ago). However, in contrast to mtDNA, which showed unidirectional transfer from Eurasia to North America prior to the last glaciation, the Y chromosome appears to have been transferred from North America to Eurasia during this period. Additional sampling is needed to confirm this pattern and to further clarify red fox Y chromosome phylogeography.

BACKGROUND: Biological causes of sex disparity seen in the prevalence of cancer, including glioblastoma (GBM), remain poorly understood. One of the considered aspects is the involvement of the sex chromosomes, especially loss of chromosome Y (LOY). METHODS: Tumors from 105 isocitrate dehydrogenase (IDH) wild type male GBM patients were tested with droplet digital PCR for copy number changes of ten genes on chromosome Y. Decreased gene expression, a proxy of gene loss, was then analyzed in 225 IDH wild type GBM derived from TCGA and overall survival in both cohorts was tested with Kaplan-Meier log-rank analysis and maximally selected rank statistics for cut-off determination. RESULTS: LOY was associated with significantly shorter overall survival (7 vs. 14.6 months, p = 0.0016), and among investigated individual genes survival correlated most prominently with loss of the sex-determining region Y gene (SRY) (10.8 vs. 14.8 months, p = 0.0031). Gene set enrichment analysis revealed that epidermal growth factor receptor, platelet-derived growth factor receptor, and MYC proto-oncogene signaling pathways are associated with low SRY expression. CONCLUSION: Our data show that deletions and reduced gene expression of chromosome Y genes, especially SRY, are associated with reduced survival of male GBM patients and connected to major susceptibility pathways of gliomagenesis.

In the seed beetle Callosobruchus maculatus, the female is the larger sex and the male is the smaller sex. However, males that are almost as large as females can also occur, which is due to a specific Y chromosome haplotype. This Y chromosome polymorphism is not expected since the Y chromosome does not recombine and has lost genetic variation as a consequence. Nevertheless, the Y chromosome manages to maintain this polymorphism. Thus, the questions asked are how this occurs and how the large male Y haplotype persists to exist since previous studies have shown how small males have the higher fitness. In this study, large males were from line SL3b Y and small males were from line SL1b Y. To answer the questions, two important measures of fitness were conducted, mating- and lifetime reproductive success, as well as lifetime-history traits of the SL1b Y and SL3b Y males. Males from line SL3b Y turned out to have a faster growth rate and a shorter development time compared to the SL1b Y males. Both the SL3b Y males with a shorter development time and the SL1b Y males with a longer development time had larger body sizes. Large males also showed to have heavier ejaculate weight and produced more offspring compared to the other male Y haplotype. However, neither of the males had higher pre-mating success. In conclusion, the two male Y haplotypes must coexist in nature since their traits are beneficial in different environments and circumstances.

Egg-laying mammals (monotremes) are the only extant mammalian outgroup to therians (marsupial and eutherian animals) and provide key insights into mammalian evolution1,2. Here we generate and analyse reference genomes of the platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus), which represent the only two extant monotreme lineages. The nearly complete platypus genome assembly has anchored almost the entire genome onto chromosomes, markedly improving the genome continuity and gene annotation. Together with our echidna sequence, the genomes of the two species allow us to detect the ancestral and lineage-specific genomic changes that shape both monotreme and mammalian evolution. We provide evidence that the monotreme sex chromosome complex originated from an ancestral chromosome ring configuration. The formation of such a unique chromosome complex may have been facilitated by the unusually extensive interactions between the multi-X and multi-Y chromosomes that are shared by the autosomal homologues in humans. Further comparative genomic analyses unravel marked differences between monotremes and therians in haptoglobin genes, lactation genes and chemosensory receptor genes for smell and taste that underlie the ecological adaptation of monotremes.

Knowledge about the connectivity among natural populations is essential to identify management units for effective conservation actions. Conservation-minded management has led to the recovery of large carnivore populations in northern Europe, possibly restoring connectivity between the two separated, but expanding brown bear (Ursus arctos) populations on the Scandinavian peninsula to the west and Karelia, a part of the large Eurasian population, to the east. The degree of connectivity between these populations has been poorly understood, therefore we investigated the extent of connectivity between the two populations using autosomal microsatellites and Y chromosome haplotypes in 924 male bears (the dispersing sex), sampled during a period of 12 years (2005–2017) across the transborder area where these two populations meet. Our results showed that the two populations are not genetically isolated as reported in earlier studies. We detected recent asymmetrical gene flow at a rate (individuals per generation) of 4.6–5.5 (1%) from Karelia into Scandinavia, whereas the rate was approximately 27.1–34.5 (8%) in the opposite direction. We estimated historical gene flow of effective number of migrants to be between 1.7 and 2.5 between the populations. Analyses of Y chromosome markers supported these results. Successful recovery and expansion of both populations led to the restoration of connectivity, however, it is asymmetric, possibly due to different recovery histories and population densities. By aligning monitoring between neighboring countries, we were able to better understand the biological processes across the relevant spatial scale.

Although the human Y chromosome has effectively shown utility in uncovering facets of human evolution and population histories, the ascertainment bias present in early Y-chromosome variant data sets limited the accuracy of diversity and TMRCA estimates obtained from them. The advent of next-generation sequencing, however, has removed this bias and allowed for the discovery of thousands of new variants for use in improving the Y-chromosome phylogeny and computing estimates that are more accurate. Here, we describe the high-coverage sequencing of the whole Y chromosome in a data set of 19 male Khoe-San individuals in comparison with existing whole Y-chromosome sequence data. Due to the increased resolution, we potentially resolve the source of haplogroup B-P70 in the Khoe-San, and reconcile recently published haplogroup A-M51 data with the most recent version of the ISOGG Y-chromosome phylogeny. Our results also improve the positioning of tentatively placed new branches of the ISOGG Y-chromosome phylogeny. The distribution of major Y-chromosome haplogroups in the Khoe-San and other African groups coincide with the emerging picture of African demographic history; with E-M2 linked to the agriculturalist Bantu expansion, E-M35 linked to pastoralist eastern African migrations, B-M112 linked to earlier east-south gene flow, A-M14 linked to shared ancestry with central African rainforest hunter-gatherers, and A-M51 potentially unique to the Khoe-San.

Large portions of eukaryotic genomes consist of transposable elements (TEs), and the establishment of transcription-repressing heterochromatin during early development safeguards genome integrity in Drosophila. Repeat-rich Y chromosomes can act as reservoirs for TEs ('toxic' Y effect), and incomplete epigenomic defenses during early development can lead to deleterious TE mobilization. Here, we contrast the dynamics of early TE activation in two Drosophila species with vastly different Y chromosomes of different ages. Zygotic TE expression is elevated in male embryos relative to females in both species, mostly due to expression of Y-linked TEs. Interestingly, male-biased TE expression diminishes across development in D. pseudoobscura, but remains elevated in D. miranda, the species with the younger and larger Y chromosome. The repeat-rich Y of D. miranda still contains many actively transcribed genes, which compromise the formation of silencing heterochromatin. Elevated TE expression results in more de novo insertions of repeats in males compared to females. This lends support to the idea that the 'toxic' Y chromosome can create a mutational burden in males when genome-wide defense mechanisms are compromised, and suggests a previously unappreciated epigenetic conflict on evolving Y chromosomes between transcription of essential genes and silencing of selfish DNA.

The Drosophila obscura species group shows dramatic variation in karyotype, including transitions among sex chromosomes. Members of the affinis and pseudoobscura subgroups contain a neo-X chromosome (a fusion of the X with an autosome), and ancestral Y genes have become autosomal in species harboring the neo-X. Detailed analysis of species in the pseudoobscura subgroup revealed that ancestral Y genes became autosomal through a translocation to the small dot chromosome. Here, we show that the Y-dot translocation is restricted to the pseudoobscura subgroup, and translocation of ancestral Y genes in the affinis subgroup likely followed a different route. We find that most ancestral Y genes have translocated to unique autosomal or X-linked locations in different taxa of the affinis subgroup, and we propose a dynamic model of sex chromosome formation and turnover in the obscura species group. Our results suggest that Y genes can find unique paths to escape unfavorable genomic environments that form after sex chromosome-autosome fusions.

The Drosophila Y chromosome is gene poor and mainly consists of silenced, repetitive DNA. Nonetheless, the Y influences expression of hundreds of genes genome-wide, possibly by sequestering key components of the heterochromatin machinery away from other positions in the genome. To test the influence of the Y chromosome on the genome-wide chromatin landscape, we assayed the genomic distribution of histone modifications associated with gene activation (H3K4me3) or heterochromatin (H3K9me2 and H3K9me3) in fruit flies with varying sex chromosome complements (X0, XY, and XYY males; XX and XXY females). Consistent with the general deficiency of active chromatin modifications on the Y, we find that Y gene dose has little influence on the genomic distribution of H3K4me3. In contrast, both the presence and the number of Y chromosomes strongly influence genome-wide enrichment patterns of repressive chromatin modifications. Highly repetitive regions such as the pericentromeres, the dot, and the Y chromosome (if present) are enriched for heterochromatic modifications in wildtype males and females, and even more strongly in X0 flies. In contrast, the additional Y chromosome in XYY males and XXY females diminishes the heterochromatic signal in these normally silenced, repeat-rich regions, which is accompanied by an increase in expression of Y-linked repeats. We find hundreds of genes that are expressed differentially between individuals with aberrant sex chromosome karyotypes, many of which also show sex-biased expression in wildtype Drosophila. Thus, Y chromosomes influence heterochromatin integrity genome-wide, and differences in the chromatin landscape of males and females may also contribute to sex-biased gene expression and sexual dimorphisms.

Heterochromatin suppresses repetitive DNA, and a loss of heterochromatin has been observed in aged cells of several species, including humans and Drosophila. Males often contain substantially more heterochromatic DNA than females, due to the presence of a large, repeat-rich Y chromosome, and male flies generally have a shorter average lifespan than females. Here we show that repetitive DNA becomes de-repressed more rapidly in old male flies relative to females, and repeats on the Y chromosome are disproportionally mis-expressed during ageing. This is associated with a loss of heterochromatin at repetitive elements during ageing in male flies, and a general loss of repressive chromatin in aged males away from pericentromeric regions and the Y. By generating flies with different sex chromosome karyotypes (XXY females and X0 and XYY males), we show that repeat de-repression and average lifespan is correlated with the number of Y chromosomes. This suggests that sex-specific chromatin differences may contribute to sex-specific ageing in flies.

Hepatocellular carcinoma (HCC) is a highly heterogeneous liver cancer with significant male biases in incidence, disease progression, and outcomes. Previous studies have suggested that genes on the Y chromosome could be expressed and exert various male-specific functions in the oncogenic processes. In particular, the RNA-binding motif on the Y chromosome (RBMY) gene is frequently activated in HCC and postulated to promote hepatic oncogenesis in patients and animal models. In the present study, immunohistochemical analyses of HCC specimens and data mining of The Cancer Genome Atlas (TCGA) database revealed that high-level RBMY expression is associated with poor prognosis and survival of the patients, suggesting that RBMY could possess oncogenic properties in HCC. To examine the immediate effect(s) of the RBMY overexpression in liver cancer cells, cell proliferation was analyzed on HuH-7 and HepG2 cells. The results unexpectedly showed that RBMY overexpression inhibited cell proliferation in both cell lines as its immediate effect, which led to vast cell death in HuH-7 cells. Transcriptome analysis showed that genes involved in various cell proliferative pathways, such as the RAS/RAF/MAP and PIP3/AKT signaling pathways, were downregulated by RBMY overexpression in HuH-7 cells. Furthermore, in vivo analyses in a mouse liver cancer model using hydrodynamic tail vein injection of constitutively active AKT and RAS oncogenes showed that RBMY abolished HCC development. These findings support the notion that Y-linked RBMY could serve dual tumor-suppressing and tumor-promoting functions, depending on the spatiotemporal and magnitude of its expression during oncogenic processes, thereby contributing to sexual dimorphisms in liver cancer.

The X chromosome and the Y chromosome are the sex chromosomes of mammals. While the X chromosome carries many genes with functions beyond sex, the Y chromosome is relatively gene poor. It serves as the trigger for development of a male embryo, with its genes having roles in testis determination and function. The sex chromosomes exist as a pair; in females, this pair are XX, and in males, XY. Two different mouse Y chromosomes were the focus of this project. The first was a transgenic fluorescent reporter Y chromosome, Ddx3y^mKate2, which was created to be used as a tool in chromosome instability research. The second was the naturally occurring Y chromosome from the A/HeJ inbred mouse strain, Y^A/HeJ. The work associated with these two Y chromosomes comprised the two studies in this project. The Ddx3y^mKate2 Y chromosome was generated by targeted insertion of a transgene cassette containing the red fluorescent protein gene, mKate2, into the mouse Y chromosome adjacent to the Ddx3y locus. This was selected as the relatively broad expression of Ddx3y indicated a permissive environment for expression of the mKate2 transgene. As male mice are XY, all male Ddx3y^mKate2 mice carried the fluorescent reporter. The mKate2 fluorescence in this strain has been previously assessed, revealing that the reporter was detectable from the preimplantation embryo, through to sexual maturity. To finalise the characterisation of the Ddx3y^mKate2 mouse, this study assessed the fluorescence in the Ddx3y^mKate2 male in advanced age. Additionally, this study characterised another transgenic reporter strain, Hprt^DsRed-Express, to serve as a comparison. To demonstrate the utility of the Ddx3y^mKate2 reporter, the Ddx3y^mKate2 Y chromosome was crossed onto two known chromosome instability backgrounds: the Trp53 knockout and Cenpagfp fusion knock-in backgrounds. Following in vivo and in vitro experiments, it was determined that the Cenpagfp background was the better background to model the Ddx3y^

The Y chromosome of Drosophila melanogaster is pivotal for male fertility. Yet, only 16 protein-coding genes reside on this chromosome. The Y chromosome is comprised primarily of heterochromatic sequences, including DNA repeats and satellite DNA, and most of the Y chromosome is still missing from the genome sequence. Furthermore, the functions of the majority of genes on the Y chromosome remain elusive. Through multiple genetic strategies, six distinct segments on the Y chromosome have been identified as "male fertility factors," and candidate gene sequences corresponding to each of these loci have been ascribed. In one case, kl-3, a specific protein coding sequence for a fertility factor has been confirmed molecularly. Here, we employed CRISPR/Cas9 to generate mutations, and RNAi, to interrogate the requirements of protein coding sequences on the Y chromosome for male fertility. We show that CRISPR/Cas9-mediated editing of kl-2 and kl-5 causes male sterility, supporting the model that these gene sequences correspond to the cognate fertility factors. We show that another gene, CCY, also functions in male fertility and may be the ks-2 fertility factor. We demonstrate that editing of kl-2, kl-3, and kl-5, and RNAi knockdown of CCY, disrupts nuclear elongation, and leads to defects in sperm individualization, including impairments in the individualization complex (IC) and synchronization. However, CRISPR/Cas9 mediated knockout of some genes on the Y chromosome, such as FDY, Ppr-Y, and Pp1-Y2 do not cause sterility, indicating that not all Y chromosome genes are essential for male fertility.

This paper is part of the celebration of the 50th anniversary of founding of the journal Hormones and Behavior, the official journal of the Society for Behavioral Neuroendocrinology. All sex differences in phenotypic development stem from the sexual imbalance in X and Y chromosomes, which are the only known differences in XX and XY zygotes. The sex chromosome genes act within cells to cause differences in phenotypes of XX and XY cells throughout the body. In the gonad, they determine the type of gonad, leading to differences in secretion of testicular vs. ovarian hormones, which cause further sex differences in tissue function. These current ideas of sexual differentiation are briefly contrasted with a hormones-only view of sexual differentiation of the last century. The multiple, independent action of diverse sex-biasing agents means that sex-biased factors can be synergistic, increasing sex differences, or compensatory, making the two sexes more equal. Several animal models have been fruitful in demonstrating sex chromosome effects, and interactions with gonadal hormones. MRI studies of human brains demonstrate variation in brain structure associated with both differences in gonadal hormones, and in the number of X and Y chromosomes. Five unanswered questions are posed as a challenge to future investigators to improve understanding of sexual differentiation throughout the body.

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.

A major sex difference in Alzheimer's disease (AD) is that men with the disease die earlier than do women. In aging and preclinical AD, men also show more cognitive deficits. Here, we show that the X chromosome affects AD-related vulnerability in mice expressing the human amyloid precursor protein (hAPP), a model of AD. XY-hAPP mice genetically modified to develop testicles or ovaries showed worse mortality and deficits than did XX-hAPP mice with either gonad, indicating a sex chromosome effect. To dissect whether the absence of a second X chromosome or the presence of a Y chromosome conferred a disadvantage on male mice, we varied sex chromosome dosage. With or without a Y chromosome, hAPP mice with one X chromosome showed worse mortality and deficits than did those with two X chromosomes. Thus, adding a second X chromosome conferred resilience to XY males and XO females. In addition, the Y chromosome, its sex-determining region Y gene (Sry), or testicular development modified mortality in hAPP mice with one X chromosome such that XY males with testicles survived longer than did XY or XO females with ovaries. Furthermore, a second X chromosome conferred resilience potentially through the candidate gene Kdm6a, which does not undergo X-linked inactivation. In humans, genetic variation in KDM6A was linked to higher brain expression and associated with less cognitive decline in aging and preclinical AD, suggesting its relevance to human brain health. Our study suggests a potential role for sex chromosomes in modulating disease vulnerability related to AD.

The impact of two mouse models is reviewed, the Four Core Genotypes and XY* models. The models are useful for determining if the causes of sex differences in phenotypes are either hormonal or sex chromosomal, or both. Used together, the models also can distinguish between the effects of X or Y chromosome genes that contribute to sex differences in phenotypes. To date, the models have been used to uncover sex chromosome contributions to sex differences in a wide variety of phenotypes, including brain and behavior, autoimmunity and immunity, cardiovascular disease, metabolism, and Alzheimer's Disease. In some cases, use of the models has been a strategy leading to discovery of specific X or Y genes that protect from or exacerbate disease. Sex chromosome and hormonal factors interact, in some cases to reduce the effects of each other. Future progress will come from more extensive application of these models, and development of similar models in other species.

The mammalian male-specific Y chromosome plays a critical role in sex determination and male fertility. However, because of its repetitive and haploid nature, it is frequently absent from genome assemblies and remains enigmatic. The Y chromosomes of great apes represent a particular puzzle: their gene content is more similar between human and gorilla than between human and chimpanzee, even though human and chimpanzee share a more recent common ancestor. To solve this puzzle, here we constructed a dataset including Ys from all extant great ape genera. We generated assemblies of bonobo and orangutan Ys from short and long sequencing reads and aligned them with the publicly available human, chimpanzee, and gorilla Y assemblies. Analyzing this dataset, we found that the genus Pan, which includes chimpanzee and bonobo, experienced accelerated substitution rates. Pan also exhibited elevated gene death rates. These observations are consistent with high levels of sperm competition in Pan Furthermore, we inferred that the great ape common ancestor already possessed multicopy sequences homologous to most human and chimpanzee palindromes. Nonetheless, each species also acquired distinct ampliconic sequences. We also detected increased chromatin contacts between and within palindromes (from Hi-C data), likely facilitating gene conversion and structural rearrangements. Our results highlight the dynamic mode of Y chromosome evolution and open avenues for studies of male-specific dispersal in endangered great ape species.

Forensic genetic laboratories perform a large amount of STR analyses of the Y chromosome, in particular to analyze the male part of complex DNA mixtures. However, the statistical interpretation of evidence retrieved from Y-STR haplotypes is challenging. Due to the uni-parental inheritance mode, Y-STR loci are connected to each other and thus haplotypes show patterns of relationship on the familial and population level. This precludes the treatment of Y-STR loci as independently inherited variables and the application of the product rule. Instead, the dependency structure of Y-STRs needs to be included in the haplotype frequency estimation process affecting also the current paradigm of a random match probability that is in the autosomal case approximated by the population frequency assuming unrelatedness of sampled individuals. Information on the degree of paternal relatedness in the suspect population as well as on the familial network is however needed to interpret Y-chromosomal results in the best possible way. The previous recommendations of the DNA commission of the ISFG on the use of Y-STRs in forensic analysis published more than a decade ago [1] cover the interpretation issue only marginally. The current recommendations address a number of topics (frequency estimators, databases, metapopulations, LR formulation, triage, rapidly mutating Y-STRs) with relevance for the Y-STR statistics and recommend a decision-based procedure, which takes into account legal requirements as well as availability of population data and statistical methods.

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1, 2, 3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800–9,000 years BP and ∼5,300–1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution.

Genomic analyses are at the center of contemporary biology. These studies heavily rely on reference genome assemblies, yet those are typically highly fragmented. Having accurate representations of complex genomes, or parts thereof, is crucial to study human and primate evolution and disease. Here, we develop and apply new sequencing strategies and technologies to improve reference assemblies. We first explore the combinatorial potential of different datasets to generate a highly improved reference for the chimpanzee, a crucial species for the study of human origins. We are able to close 77% of the over 159.000 remaining gaps in the previous iteration of this species’ assembly and increase continuity by more than 750%. We then go on to develop a workflow to assemble the first human Y chromosome of African ancestry, using native flow-sorted chromosomes sequenced on a Nanopore device. We are able to assemble the Y chromosome to a reference grade quality and achieve unprecedented sequence resolution across structurally complex regions. These results open new avenues for comparative studies including the chimpanzee genome or human Y chromosomes.

Cannabis sativa L. is an important yet controversial plant with a long history of recreational, medicinal, industrial, and agricultural use, and together with its sister genus Humulus, it represents a group of plants with a myriad of academic, agricultural, pharmaceutical, industrial, and social interests. We have performed a meta-analysis of pooled published genomics data, andwe present a comprehensive literature review on the evolutionary history of Cannabis and Humulus, including medicinal and industrial applications. We demonstrate that current Cannabis genome assemblies are incomplete, with sim10% missing, 10-25% unmapped, and 45S and 5S ribosomal DNA clusters as well as centromeres/satellite sequences not represented. These assemblies are also ordered at a low resolution, and their consensus quality clouds the accurate annotation of complete, partial, and pseudogenized gene copies. Considering the importance of genomics in the development of any crop, this analysis underlines the need for a coordinated effort to quantify the genetic and biochemical diversity of this species.

The Drosophila Y chromosome is gene poor and mainly consists of silenced, repetitive DNA. Nonetheless, the Y influences expression of hundreds of genes genome-wide, possibly by sequestering key components of the heterochromatin machinery away from other positions in the genome. To test the influence of the Y chromosome on the genome-wide chromatin landscape, we assayed the genomic distribution of histone modifications associated with gene activation (H3K4me3) or heterochromatin (H3K9me2 and H3K9me3) in fruit flies with varying sex chromosome complements (X0, XY, and XYY males; XX and XXY females). Consistent with the general deficiency of active chromatin modifications on the Y, we find that Y gene dose has little influence on the genomic distribution of H3K4me3. In contrast, both the presence and the number of Y chromosomes strongly influence genome-wide enrichment patterns of repressive chromatin modifications. Highly repetitive regions such as the pericentromeres, the dot, and the Y chromosome (if present) are enriched for heterochromatic modifications in wildtype males and females, and even more strongly in X0 flies. In contrast, the additional Y chromosome in XYY males and XXY females diminishes the heterochromatic signal in these normally silenced, repeat-rich regions, which is accompanied by an increase in expression of Y-linked repeats. We find hundreds of genes that are expressed differentially between individuals with aberrant sex chromosome karyotypes, many of which also show sex-biased expression in wildtype Drosophila. Thus, Y chromosomes influence heterochromatin integrity genome-wide, and differences in the chromatin landscape of males and females may also contribute to sex-biased gene expression and sexual dimorphisms.

Heterochromatin suppresses repetitive DNA, and a loss of heterochromatin has been observed in aged cells of several species, including humans and Drosophila. Males often contain substantially more heterochromatic DNA than females, due to the presence of a large, repeat-rich Y chromosome, and male flies generally have a shorter average lifespan than females. Here we show that repetitive DNA becomes de-repressed more rapidly in old male flies relative to females, and repeats on the Y chromosome are disproportionally mis-expressed during ageing. This is associated with a loss of heterochromatin at repetitive elements during ageing in male flies, and a general loss of repressive chromatin in aged males away from pericentromeric regions and the Y. By generating flies with different sex chromosome karyotypes (XXY females and X0 and XYY males), we show that repeat de-repression and average lifespan is correlated with the number of Y chromosomes. This suggests that sex-specific chromatin differences may contribute to sex-specific ageing in flies.

Analyses of Y chromosome haplotypes uniquely provide a paternal picture of evolutionary histories and offer a very useful contrast to studies based on maternally inherited mitochondrial DNA (mtDNA). Here we used a bioinformatic approach based on comparison of male and female sequence coverage to identify 4.7 Mb from the grey wolf (Canis lupis) Y chromosome, probably representing most of the male-specific, nonampliconic sequence from the euchromatic part of the chromosome. We characterized this sequence and then identified approximate to 1,500 Y-linked single nucleotide polymorphisms in a sample of 145 resequenced male wolves, including 75 Finnish wolf genomes newly sequenced in this study, and in 24 dogs and eight other canids. We found 53 Y chromosome haplotypes, of which 26 were seen in grey wolves, that clustered in four major haplogroups. All four haplogroups were represented in samples of Finnish wolves, showing that haplogroup lineages were not partitioned on a continental scale. However, regional population structure was indicated because individual haplotypes were never shared between geographically distant areas, and genetically similar haplotypes were only found within the same geographical region. The deepest split between grey wolf haplogroups was estimated to have occurred 125,000 years ago, which is considerably older than recent estimates of the time of divergence of wolf populations. The distribution of dogs in a phylogenetic tree of Y chromosome haplotypes supports multiple domestication events, or wolf paternal introgression, starting 29,000 years ago. We also addressed the disputed origin of a recently founded population of Scandinavian wolves and observed that founding as well as most recent immigrant haplotypes were present in the neighbouring Finnish population, but not in sequenced wolves from elsewhere in the world, or in dogs.

Widespread loss of genes on the Y is considered a hallmark of sex chromosome differentiation. Here we show that the initial stages of Y evolution are driven by massive amplification of distinct classes of genes. The neo-Y chromosome of Drosophila miranda initially contained about 3,000 protein-coding genes, but has gained over 3,200 genes since its formation about 1.5 million years ago primarily by tandem amplification of protein-coding genes ancestrally present on this chromosome. We show that distinct evolutionary processes may account for this drastic increase in gene number on the Y. Testis-specific and dosage-sensitive genes appear to have amplified on the Y to increase male fitness. A distinct class of meiosis-related multi-copy Y genes independently co-amplified on the X, and their expansion is probably driven by conflicts over segregation. Co-amplified X/Y genes are highly expressed in testis, enriched for meiosis and RNA interference functions and are frequently targeted by small RNAs in testis. This suggests that their amplification is driven by X versus Y antagonism for increased transmission, where sex chromosome drive suppression is probably mediated by sequence homology between the suppressor and distorter through the RNA interference mechanism. Thus, our analysis suggests that newly emerged sex chromosomes are a battleground for sexual and meiotic conflict.

The horse reference genome from the Thoroughbred mare Twilight has been available for a decade and, together with advances in genomics technologies, has led to unparalleled developments in equine genomics. At the core of this progress is the continuing improvement of the quality, contiguity and completeness of the reference genome, and its functional annotation. Recent achievements include the release of the next version of the reference genome (EquCab3.0) and generation of a reference sequence for the Y chromosome. Horse satellite-free centromeres provide unique models for mammalian centromere research. Despite extremely low genetic diversity of the Y chromosome, it has been possible to trace patrilines of breeds and pedigrees and show that Y variation was lost in the past approximately 2300 years owing to selective breeding. The high-quality reference genome has led to the development of three different SNP arrays and WGSs of almost 2000 modern individual horses. The collection of WGS of hundreds of ancient horses is unique and not available for any other domestic species. These tools and resources have led to global population studies dissecting the natural history of the species and genetic makeup and ancestry of modern breeds. Most importantly, the available tools and resources, together with the discovery of functional elements, are dissecting molecular causes of a growing number of Mendelian and complex traits. The improved understanding of molecular underpinnings of various traits continues to benefit the health and performance of the horse whereas also serving as a model for complex disease across species.