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Man-Xiu Li, Li-Ting Jin, Tie-Jun Wang, Yao-Jun Feng, Cui-Ping Pan, Dei-Mian Zhao, Jun Shao Department of Breast Cancer, Hubei Cancer Hospital, Wuhan, People’s Republic of China Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome and limited treatment options. Lacking molecular targets, chemotherapy is the main adjuvant treatment for TNBC patients. Materials and methods: To explore potential therapeutic targets for TNBC, we analyzed three microarray datasets (GSE38959, GSE45827, and GSE65194) derived from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between TNBC and normal tissue. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery to identify the pathways and functional annotation of DEGs. Protein–protein interaction of these DEGs was analyzed based on the Search Tool for the Retrieval of Interacting Genes database and visualized by Cytoscape software. In addition, we used the online Kaplan–Meier plotter survival analysis tool to evaluate the prognostic value of hub genes expression in breast cancer patients. Results: A total of 278 upregulated DEGs and 173 downregulated DEGs were identified. Among them, ten hub genes with a high degree of connectivity were picked out. Overexpression of these hub genes was associated with unfavorable prognosis of breast cancer, especially, CCNB1 overexpression was observed and indicated poor outcome of TNBC. Conclusion: Our study suggests that CCNB1 was overexpressed in TNBC compared with normal breast tissue, and overexpression of CCNB1 was an unfavorable prognostic factor of TNBC patients. Further study is needed to explore the value of CCNB1 in the treatment of TNBC. Keywords: triple-negative breast cancer, hub genes, expression profiling data, CCNB1

Male-male competition and female mate choice based on ornamentation and genetic traits are the main drivers of animal sexual selection and group spawning. If male-male competition is intense, males with specific phenotypes should have advantages in breeding success or occupying superior mating positions. If female choice is important, females should have preferences for mate relatedness or males with good genes or optimal genetic compatibility against themselves. To detect the intensities of male-male competition and female choice and test the good genes and genetic compatibility hypotheses, we observed breeding behaviors, measured individual body lengths and breeding success indicators, and calculated male genetic heterozygosity, male–female relatedness, and genetic dissimilarity in an Omei treefrog (Rhacophorus omeimontis) population in Badagongshan, China. Our analyses showed that larger males obtained larger mates, had more mating opportunities, occupied better amplectant positions, and produced more offspring. However, females showed no inbreeding/outbreeding bias in mate choice, and the good genes and genetic compatibility hypotheses were not supported in female selection on mates and amplectant positions. We considered male-male competition as the main driver of sexual selection and group spawning in this prolonged mating species because the cost of choosing mates with specific genetic traits may be high for females. Male-male competition and female mate choice are the main drivers of animal sexual selection and mating behaviors. However, their impacts on the evolution of mating system are not yet quite clear. By studying the Omei treefrog, a Chinese endemic anuran species with common group spawning behaviors, this research posed the importance of male-male competition and female mate choice and discussed the mechanisms of sexual selection and multiple mating, which are the most essential and debated issues in evolutionary biology and behavioral ecology. We found that, in this prolonged mating and lek-patterned species, male-male competition is the main driver of sexual selection and group spawning. Larger males can get larger females, have more breeding opportunities, occupy better amplectant positions, and thus, obtain greater numbers of offspring. Whereas, females have no significant preferences on ornamentation and genetic traits of their males or mating positions, and the inferior males “make the best of a bad lot” by joining mating pairs to produce mating groups. Our study provides empirical evidence of reproductive mechanisms of amphibian species and could advance the understandings on the evolution of animals’ sexual selection and mating system.

Sexual selection is critical to both reproduction and evolution. The effects of male–male competition and female choice regarding body size have been examined in a large number of taxa, including toad species. Males and females have different optimal reproductive strategies, achieving breeding advantages in discrepant ways. Further, the relative contributions of intra- and inter-sexual size selection vary among species. Thus, to understand the mechanisms affecting mating success, it is important to consider both male–male and male–female interactions simultaneously and elucidate their interrelationship. In this study, we measured body sizes of all mated and unmated individuals in a population of Asiatic toad (Bufo gargarizans) and counted fertilized eggs of several clutches. Based on correlation and regression techniques, we tested for female choice and intra-sexual competition among males relative to body size gradients, and we compared the relative importance of these two processes for mating success. Our results reveal that male–male competition and female choice simultaneously contribute to sexual selection in toads. Furthermore, both interactions are most intense among smaller toads. The synergistic trends of male–male competition and female choice support the mutual mate choice hypothesis and works to stabilize body size in B. gargarizans. Normal distributions of breeding success relative to body size were detected for both sexes, suggesting that medium-sized individuals enjoy a reproductive advantage in the population studied.

Animal skin, which is the tissue that directly contacts the external surroundings, has evolved diverse functions to adapt to various environments. Amphibians represent the transitional taxon from aquatic to terrestrial life. Exploring the molecular basis of their skin function and adaptation is important to understand the survival and evolutionary mechanisms of vertebrates. However, comprehensive studies on the molecular mechanisms of skin functions in amphibians are scarce. In this study, we sequenced the skin transcriptomes of seven anurans belonging to three families and compared the similarities and differences in expressed genes and proteins. Unigenes and pathways related to basic biological processes and special functions, such as defense, immunity and respiration, were enriched in functional annotations. A total of 108 antimicrobial peptides were identified. The highly expressed genes were similar in species of the same family but were different among families. Additionally, the positively selected orthologous groups were involved in biosynthesis, metabolism, immunity and defense processes. This study is the first to generate extensive transcriptome data for the skin of seven anurans and provides unigenes and pathway candidates for further studies on amphibian skin function and adaptation.

In order to achieve a thorough coverage of the basal lineages in the Chinese matrilineal pool, we have sequenced the mitochondrial DNA (mtDNA) control region and partial coding region segments of 6,093 mtDNAs sampled from 84 populations across China. By comparing with the available complete mtDNA sequences, 194 of those mtDNAs could not be firmly assigned into the available haplogroups. Completely sequencing 51 representatives selected from these unclassified mtDNAs identified a number of novel lineages, including five novel basal haplogroups that directly emanate from the Eurasian founder nodes (M and N). No matrilineal contribution from the archaic hominid was observed. Subsequent analyses suggested that these newly identified basal lineages likely represent the genetic relics of modern humans initially peopling East Asia instead of being the results of gene flow from the neighboring regions. The observation that most of the newly recognized mtDNA lineages have already differentiated and show the highest genetic diversity in southern China provided additional evidence in support of the Southern Route peopling hypothesis of East Asians. Specifically, the enrichment of most of the basal lineages in southern China and their rather ancient ages in Late Pleistocene further suggested that this region was likely the genetic reservoir of modern humans after they entered East Asia.

Background Comparison of major histocompatibility complex (MHC) genes across vertebrate species can reveal molecular mechanisms underlying the evolution of adaptive immunity-related proteins. As the first terrestrial tetrapods, amphibians deserve special attention because of their exposure to probably increased spectrum of microorganisms compared with ancestral aquatic fishes. Knowledge regarding the evolutionary patterns and mechanisms associated with amphibian MHC genes remains limited. The goal of the present study was to isolate MHC class I genes from two Rhacophoridae species (Rhacophorus omeimontis and Polypedates megacephalus) and examine their evolution. Results We identified 27 MHC class I alleles spanning the region from exon 2 to 4 in 38 tree frogs. The available evidence suggests that these 27 sequences all belong to classical MHC class I (MHC Ia) genes. Although several anuran species only display one MHC class Ia locus, at least two or three loci were observed in P. megacephalus and R. omeimontis, indicating that the number of MHC class Ia loci varies among anuran species. Recombination events, which mainly involve the entire exons, played an important role in shaping the genetic diversity of the 27 MHC class Ia alleles. In addition, signals of positive selection were found in Rhacophoridae MHC class Ia genes. Amino acid sites strongly suggested by program to be under positive selection basically accorded with the putative antigen binding sites deduced from crystal structure of human HLA. Phylogenetic relationships among MHC class I alleles revealed the presence of trans-species polymorphisms. Conclusions In the two Rhacophoridae species (1) there are two or three MHC class Ia loci; (2) recombination mainly occurs between the entire exons of MHC class Ia genes; (3) balancing selection, gene duplication and recombination all contribute to the diversity of MHC class Ia genes. These findings broaden our knowledge on the evolution of amphibian MHC systems.

Himalayas was believed to be a formidably geographical barrier between South and East Asia. The observed high frequency of the East Eurasian paternal lineages in Nepal led some researchers to suggest that these lineages were introduced into Nepal from Tibet directly; however, it is also possible that the East Eurasian genetic components might trace their origins to northeast India where abundant East Eurasian maternal lineages have been detected. To trace the origin of the Nepalese maternal genetic components, especially those of East Eurasian ancestry, and then to better understand the role of the Himalayas in peopling Nepal, we have studied the matenal genetic composition extensively, especially the East Eurasian lineages, in Nepalese and its surrounding populations. Our results revealed the closer affinity between the Nepalese and the Tibetans, specifically, the Nepalese lineages of the East Eurasian ancestry generally are phylogenetically closer with the ones from Tibet, albeit a few mitochondrial DNA haplotypes, likely resulted from recent gene flow, were shared between the Nepalese and northeast Indians. It seems that Tibet was most likely to be the homeland for most of the East Eurasian in the Nepalese. Taking into account the previous observation on Y chromosome, now it is convincing that bearer of the East Eurasian genetic components had entered Nepal across the Himalayas around 6 kilo years ago (kya), a scenario in good agreement with the previous results from linguistics and archeology.

We agree with van Oven (1) that a uniform mitochondrial (mt)DNA haplogroup nomenclature is indispensable for the future studies, and we actually propagated the same idea a few years ago (2). The current conflicts regarding the Asian haplogroup nomenclature (1) were essentially caused by publication delay: at the time when we submitted the manuscript (July 14, 2009), there was no conflict between the haplogroup system in our paper (3) and PhyloTree (mtDNA tree Build 5; http://www.phylotree.org/) to which we referred. To avoid similar problems in the future, a possible solution is that researchers in the mtDNA field indicate to van Oven (1) on submission of a paper that certain haplogroup names are being introduced, so that other researchers would at least not choose the same code for their newly identified haplogroups. The blocked names (possibly with some further information) could then be shown in the bulk mtDNA tree on that website.

Due to its numerous environmental extremes, the Tibetan Plateau—the world's highest plateau—is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics.

Background Archaeological studies have revealed a series of cultural changes around the Last Glacial Maximum in East Asia; whether these changes left any signatures in the gene pool of East Asians remains poorly indicated. To achieve deeper insights into the demographic history of modern humans in East Asia around the Last Glacial Maximum, we extensively analyzed mitochondrial DNA haplogroup M9a'b, a specific haplogroup that was suggested to have some potential for tracing the migration around the Last Glacial Maximum in East Eurasia. Results A total of 837 M9a'b mitochondrial DNAs (583 from the literature, while the remaining 254 were newly collected in this study) pinpointed from over 28,000 subjects residing across East Eurasia were studied here. Fifty-nine representative samples were further selected for total mitochondrial DNA sequencing so we could better understand the phylogeny within M9a'b. Based on the updated phylogeny, an extensive phylogeographic analysis was carried out to reveal the differentiation of haplogroup M9a'b and to reconstruct the dispersal histories. Conclusions Our results indicated that southern China and/or Southeast Asia likely served as the source of some post-Last Glacial Maximum dispersal(s). The detailed dissection of haplogroup M9a'b revealed the existence of an inland dispersal in mainland East Asia during the post-glacial period. It was this dispersal that expanded not only to western China but also to northeast India and the south Himalaya region. A similar phylogeographic distribution pattern was also observed for haplogroup F1c, thus substantiating our proposition. This inland post-glacial dispersal was in agreement with the spread of the Mesolithic culture originating in South China and northern Vietnam.