Gene duplication and the origins of morphological complexity in pancrustacean eyes, a genomic approach

<p>Abstract</p> <p>Background</p> <p>Duplication and divergence of genes and genetic networks is hypothesized to be a major driver of the evolution of complexity and novel features. Here, we examine the history of genes and genetic networks in the context of eye evolution by using new approaches to understand patterns of gene duplication during the evolution of metazoan genomes. We hypothesize that 1) genes involved in eye development and phototransduction have duplicated and are retained at higher rates in animal clades that possess more distinct types of optical design; and 2) genes with functional relationships were duplicated and lost together, thereby preserving genetic networks. To test these hypotheses, we examine the rates and patterns of gene duplication and loss evident in 19 metazoan genomes, including that of <it>Daphnia pulex </it>- the first completely sequenced crustacean genome. This is of particular interest because the pancrustaceans (hexapods+crustaceans) have more optical designs than any other major clade of animals, allowing us to test specifically whether the high amount of disparity in pancrustacean eyes is correlated with a higher rate of duplication and retention of vision genes.</p> <p>Results</p> <p>Using protein predictions from 19 metazoan whole-genome projects, we found all members of 23 gene families known to be involved in eye development or phototransduction and deduced their phylogenetic relationships. This allowed us to estimate the number and timing of gene duplication and loss events in these gene families during animal evolution. When comparing duplication/retention rates of these genes, we found that the rate was significantly higher in pancrustaceans than in either vertebrates or non-pancrustacean protostomes. Comparing patterns of co-duplication across Metazoa showed that while these eye-genes co-duplicate at a significantly higher rate than those within a randomly shuffled matrix, many genes with known functional relationships in model organisms did not co-duplicate more often than expected by chance.</p> <p>Conclusions</p> <p>Overall, and when accounting for factors such as differential rates of whole-genome duplication in different groups, our results are broadly consistent with the hypothesis that genes involved in eye development and phototransduction duplicate at a higher rate in Pancrustacea, the group with the greatest variety of optical designs. The result that these genes have a significantly high number of co-duplications and co-losses could be influenced by shared functions or other unstudied factors such as synteny. Since we did not observe co-duplication/co-loss of genes for all known functional modules (e.g. specific regulatory networks), the interactions among suites of known co-functioning genes (modules) may be plastic at the temporal scale of analysis performed here. Other factors in addition to gene duplication - such as cis-regulation, heterotopy, and co-option - are also likely to be strong factors in the diversification of eye types.</p

Facilitates Chromatin Transcription Complex Is an “Accelerator” of Tumor Transformation and Potential Marker and Target of Aggressive Cancers

SummaryThe facilitates chromatin transcription (FACT) complex is involved in chromatin remodeling during transcription, replication, and DNA repair. FACT was previously considered to be ubiquitously expressed and not associated with any disease. However, we discovered that FACT is the target of a class of anticancer compounds and is not expressed in normal cells of adult mammalian tissues, except for undifferentiated and stem-like cells. Here, we show that FACT expression is strongly associated with poorly differentiated aggressive cancers with low overall survival. In addition, FACT was found to be upregulated during in vitro transformation and to be necessary, but not sufficient, for driving transformation. FACT also promoted survival and growth of established tumor cells. Genome-wide mapping of chromatin-bound FACT indicated that FACT’s role in cancer most likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses

Frequency of breast cancer subtypes among African American women in the AMBER consortium

Abstract Background Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. The aim of this study was to optimize tumor classification using automated methods in order to describe subtype frequency in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Methods Using immunohistochemistry (IHC), we quantified the expression of ER, PR, HER2, the proliferation marker Ki67, and two basal-like biomarkers, epidermal growth factor receptor (EGFR) and cytokeratin (CK)5/6, in 1381 invasive breast tumors from African American women. RNA-based (prediction analysis of microarray 50 (PAM50)) subtype, available for 574 (42%) cases, was used to optimize classification. Subtype frequency was calculated, and associations between subtype and tumor characteristics were estimated using logistic regression. Results Relative to ER, PR and HER2 from medical records, central IHC staining and the addition of Ki67 or combined tumor grade improved accuracy for classifying PAM50-based luminal subtypes. Few triple negative cases (< 2%) lacked EGFR and CK5/6 expression, thereby providing little improvement in accuracy for identifying basal-like tumors. Relative to luminal A subtype, all other subtypes had higher combined grade and were larger, and ER-/HER2+ tumors were more often lymph node positive and late stage tumors. The frequency of basal-like tumors was 31%, exceeded only slightly by luminal A tumors (37%). Conclusions Our findings indicate that automated IHC-based classification produces tumor subtype frequencies approximating those from PAM50-based classification and highlight high frequency of basal-like and low frequency of luminal A breast cancer in a large study of African American women

Patterns of Intraspecific DNA Variation in the Daphnia Nuclear Genome

Understanding nucleotide variation in natural populations has been a subject of great interest for decades. However, many taxonomic groups, especially those with atypical life history attributes remain unstudied, and Drosophila is the only arthropod genus for which DNA polymorphism data are presently abundant. As a result of the recent release of the complete genome sequence and a wide variety of new genomic resources, the Daphnia system is quickly becoming a promising new avenue for expanding our knowledge of nucleotide variation in natural populations. Here, we examine nucleotide variation in six protein-coding loci for Daphnia pulex and its congeners with particular emphasis on D. pulicaria, the closest extant relative of D. pulex. Levels of synonymous intraspecific variation, πs, averaged 0.0136 for species in the Daphnia genus, and are slightly lower than most prior estimates in invertebrates. Tests of neutrality indicated that segregating variation conforms to neutral model expectations for the loci that we examined in most species, while Ka/Ks ratios revealed strong purifying selection. Using a full maximum-likelihood coalescent-based method, the ratio of the recombination rate to the mutation rate (c/u), averaged 0.5255 for species of the Daphnia genus. Lastly, a divergence population-genetics approach was used to investigate gene flow and divergence between D. pulex and D. pulicaria

Rates of Recombination in the Ribosomal DNA of Apomictically Propagated Daphnia obtusa Lines

Ribosomal (r)DNA undergoes concerted evolution, the mechanisms of which are unequal crossing over and gene conversion. Despite the fundamental importance of these mechanisms to the evolution of rDNA, their rates have been estimated only in a few model species. We estimated recombination rate in rDNA by quantifying the relative frequency of intraindividual length variants in an expansion segment of the 18S rRNA gene of the cladoceran crustacean, Daphnia obtusa, in four apomictically propagated lines. We also used quantitative PCR to estimate rDNA copy number. The apomictic lines were sampled every 5 generations for 90 generations, and we considered each significant change in the frequency distribution of length variants between time intervals to be the result of a recombination event. Using this method, we calculated the recombination rate for this region to be 0.02–0.06 events/generation on the basis of three different estimates of rDNA copy number. In addition, we observed substantial changes in rDNA copy number within and between lines. Estimates of haploid copy number varied from 53 to 233, with a mean of 150. We also measured the relative frequency of length variants in 30 lines at generations 5, 50, and 90. Although length variant frequencies changed significantly within and between lines, the overall average frequency of each length variant did not change significantly between the three generations sampled, suggesting that there is little or no bias in the direction of change due to recombination

Transcontinental Phylogeography of the <em>Daphnia pulex</em> Species Complex

<div><p><em>Daphnia pulex</em> is quickly becoming an attractive model species in the field of ecological genomics due to the recent release of its complete genome sequence, a wide variety of new genomic resources, and a rich history of ecological data. Sequences of the mitochondrial <em>NADH dehydrogenase</em> subunit 5 and <em>cytochrome</em> c <em>oxidase</em> subunit 1 genes were used to assess the global phylogeography of this species, and to further elucidate its phylogenetic relationship to other members of the <em>Daphnia pulex</em> species complex. Using both newly acquired and previously published data, we analyzed 398 individuals from collections spanning five continents. Eleven strongly supported lineages were found within the <em>D. pulex</em> complex, and one lineage in particular, panarctic <em>D. pulex</em>, has very little phylogeographical structure and a near worldwide distribution. Mismatch distribution, haplotype network, and population genetic analyses are compatible with a North American origin for this lineage and subsequent spatial expansion in the Late Pleistocene. In addition, our analyses suggest that dispersal between North and South America of this and other species in the <em>D. pulex</em> complex has occurred multiple times, and is predominantly from north to south. Our results provide additional support for the evolutionary relationships of the eleven main mitochondrial lineages of the <em>D. pulex</em> complex. We found that the well-studied panarctic <em>D. pulex</em> is present on every continent except Australia and Antarctica. Despite being geographically very widespread, there is a lack of strong regionalism in the mitochondrial genomes of panarctic <em>D. pulex</em> – a pattern that differs from that of most studied cladocerans. Moreover, our analyses suggest recent expansion of the panarctic <em>D. pulex</em> lineage, with some continents sharing haplotypes. The hypothesis that hybrid asexuality has contributed to the recent and unusual geographic success of the panarctic <em>D. pulex</em> lineage warrants further study.</p> </div

Consensus Bayesian phylogeny of the <i>Daphnia species</i> complex based on the mitochondrial COX1 gene.

<p>The alignment contains 52 sequences of length 552 nt with 151 polymorphic positions of which 112 are phylogenetically informative. Nine of the 12 lineages in the <i>Daphnia pulex</i> species complex, including all three South American lineages, are represented. The tree is rooted through the midpoint. Numbers at the nodes are Bayesian posterior probabilities and are not shown if less than 0.80. Branch colors correspond to continents as follows: green = Europe, blue = North America, red = South America. Individual CT-18 was collected from Connecticut, USA.</p

Consensus Bayesian phylogeny of the <i>Daphnia pulex</i> species complex based on the mitochondrial ND5 and COX1 genes.

<p>The alignment contains 95 sequences consisting of 762 nt of ND5 and 1386 nt of COX1 with 321 polymorphic positions of which 204 are phylogenetically informative. The tree is rooted through the midpoint. Posterior probabilities are indicated on the nodes of the tree and are not shown if less than 0.80. Taxon colors represent geographic locations as follows: black = North America, blue = east Asia, red = South America.</p