For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ~1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.

Homologous synteny blocks (HSBs) and evolutionary breakpoint regions (EBRs) in mammalian chromosomes are enriched for distinct DNA features, contributing to distinct phenotypes. To reveal HSB and EBR roles in avian evolution, we performed a sequence-based comparison of 21 avian and 5 outgroup species using recently sequenced genomes across the avian family tree and a newly-developed algorithm. We identified EBRs and HSBs in ancestral bird, archosaurian (bird, crocodile, and dinosaur), and reptile chromosomes. Genes involved in the regulation of gene expression and biosynthetic processes were preferably located in HSBs, including for example, avian-specific HSBs enriched for genes involved in limb development. Within birds, some lineage-specific EBRs rearranged genes were related to distinct phenotypes, such as forebrain development in parrots. Our findings provide novel evolutionary insights into genome evolution in birds, particularly on how chromosome rearrangements likely contributed to the formation of novel phenotypes.

High-quality genome assembly of ancient asexual rotifer reveals homologous chromosomes that frequently recombine.

A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis. The differential gene expression analysis using non-parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down-regulated genes in HCC compared to controls. The list of top differentially expressed genes mainly consists of tumor/cancer associated genes, such as AFP, THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly associated with cell cycle pathways. In total, 59 kinases associated genes were found over-expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1, CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using consensus clustering method. Each subtype was unique in terms of gene expression, pathway enrichment and median survival. Conclusively, this study has exposed a number of interesting genes which can be exploited in future as potential markers of HCC, diagnostic as well as prognostic and subtype classification may guide for improved and specific therapy.

The several hundreds of species of bdelloid rotifers are notorious because they represent an ancient clade comprising only asexual lineages 1 . Moreover, most bdelloid species have the ability to withstand complete desiccation and high doses of ionizing radiation, being able to repair their DNA after massive genome breakage 2 . To better understand the impact of long-term asexuality and DNA breakage on genome evolution, a telomere-to-tolemere reference genome assembly of a bdelloid species is critical 3, 4 . Here we present the first, high quality chromosome-scale genome assembly for the bdelloid A. vaga validated using three complementary assembly procedures combined with chromosome conformation capture (Hi-C) data. The different assemblies reveal the same genome architecture and using fluorescent in situ hybridization (FISH), we demonstrate that the A. vaga genome is composed of six pairs of homologous chromosomes, compatible with meiosis. Moreover, the synteny between homoeologous (or ohnologous) chromosomes is also preserved, confirming their paleotetraploidy. The diploid genome structure of A. vaga and the presence of very long homozygous tracts show that recombination between homologous chromosomes occurs in this ancient asexual scandal, either during DSB repair or during meiotic pairing. These homozygosity tracts are mainly observed towards the chromosome ends in the clonal A. vaga suggesting signatures of a parthenogenetic mode of reproduction equivalent to central fusion automixis, in which homologous chromosomes are not segregated during the meiotic division.Bdelloid rotifers are a notorious clade of ancient asexual animals. However, both its longevity (>60 My) and diversity 1 contradicts the expectation that obligatory parthenogenetic animal lineages are evolutionary dead-ends. Historical observations 2 (or lack thereof) have produced a consensus that bdelloid rotifers are strictly parthenogenetic without any meiosis (e.g. no 3 males or hermaphrodites 1 , ameiotic genome structure in the model species Adineta vaga 3 , apomictic oogenesis 5, 6 ). However, 4 recent studies brought doubt regarding the supposed absence of meiotic recombination in these microscopic animals. These 5 include a drop of linkage disequilibrium with increasing distance between loci in A. vaga 7 , signatures of gene conversion 3, 8 , 6 heterozygosity levels falling within the range observed for sexual metazoans 3, 4, 9 and reports of allele sharing between bdelloid 7 individuals 7, 10-12 . 8In addition to its asexual evolution, the bdelloid rotifer A. vaga also became a model species for its extreme resistance to 9 desiccation and radiation, with implications for space research. Both prolonged desiccation and radiation induce oxidative 10 1 stress and massive genome breakage that A. vaga seem to handle well, maintaining high survival and fecundity rates while 11 efficiently repairing its DNA double strand breaks (DSBs) 2 . The exact nature of their DSB repair mechanism remains unknown, 12 but homologous recombination (HR) should ...

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ABCB5 is an ABC transporter that was shown to confer low-level multidrug resistance in cancer. In this study, we show that ABCB5 was mutated in 13.75% of the 640 melanoma samples analyzed. Besides nonsense mutations, two mutation hotspots were found in the ABCB5 protein, in the drug-binding pocket and the nucleotide-binding domains. Four mutations, which are representative of the mutation pattern, were selected. ATPase assays showed that these mutations resulted in a decrease in basal ATP hydrolysis by ABCB5. To select informative melanoma cell lines, mutational profiles of the clinical samples were further analyzed. This study showed mutations in the tumor suppressor CDKN2A gene and the NRAS oncogene in 62.5% and 75%, respectively of the samples that had mutations in the ABCB5 gene. No mutation was found in the tumor suppressor PTEN gene, whereas the activating V600E mutation in the BRAF oncogene was found in 25% of the samples with a mutated ABCB5 gene. Studies in four melanoma cell lines with various genetic backgrounds showed an increase in the proliferation and migration capacity of mutant ABCB5-expressing cells, suggesting that ABCB5 plays a role in the development of melanoma as a tumor suppressor gene.