To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203). Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

In eukaryotes, karyopherin ␤ superfamily proteins mediate nucleocytoplasmic transport of macromolecules. We investigated the evolutionary and transcriptional patterns of these proteins using bioinformatics approaches. No obvious homologs were found in prokaryotes, but an extensive set of ␤-karyopherin proteins was found in yeast. Among 14 ␤-karyopherins of Saccharomyces cerevisiae, eight corresponded to their human orthologs directly without diversification, two were lost, and the remaining four proteins exhibited gene duplications by different mechanisms. We also identified ␤-karyopherin orthologs in Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Xenopus tropicalis, Gallus gallus, and Mus musculus. ␤-Karyopherins were ubiquitously but nonuniformly expressed in distinct cells and tissues. In yeast and mice, the titer of some ␤-karyopherin transcripts appeared to be regulated both during the cell cycle and during development. Further virtual analysis of promoter binding elements suggested that the transcription factors SP1, NRF-2, HEN-1, RREB-1, and nuclear factor Y regulate expression of most ␤-karyopherin genes.

Chaetothyriales is an ascomycetous order within Eurotiomycetes. The order is particularly known through the black yeasts and filamentous relatives that cause opportunistic infections in humans. All species in the order are consistently melanized. Ecology and habitats of species are highly diverse, and often rather extreme in terms of exposition and toxicity. Families are defined on the basis of evolutionary history, which is reconstructed by time of divergence and concepts of comparative biology using stochastical character mapping and a multi-rate Brownian motion model to reconstruct ecological ancestral character states. Ancestry is hypothesized to be with a rock-inhabiting life style. Ecological disparity increased significantly in late Jurassic, probably due to expansion of cytochromes followed by colonization of vacant ecospaces. Dramatic diversification took place subsequently, but at a low level of innovation resulting in strong niche conservatism for extant taxa. Families are ecologically different in degrees of specialization. One of the clades has adapted ant domatia, which are rich in hydrocarbons. In derived families, similar processes have enabled survival in domesticated environments rich in creosote and toxic hydrocarbons, and this ability might also explain the pronounced infectious ability of vertebrate hosts observed in these families. Conventional systems of morphological classification poorly correspond with recent phylogenetic data. Species are hypothesized to have low competitive ability against neighboring microbes, which interferes with their laboratory isolation on routine media. The dataset is unbalanced in that a large part of the extant biodiversity has not been analyzed by molecular methods, novel taxonomic entities being introduced at a regular pace. Our study comprises all available species sequenced to date for LSU and ITS, and a nomenclatural overview is provided. A limited number of species could not be assigned to any extant family.