In Science this week, Richard Green at the Max-Planck Institute for Evolutionary Anthropology and his international colleagues report their draft sequence of the Neandertal genome, composed of more than four billion nucleotides from three individuals. When compared to the genomes of five present-day humans from around the globe, Green et al. write they "identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development." The team suggests that future analyses of the Neandertal genome will help to elucidate "further insights into the origins and early history of present-day humans."
In a related report, Max-Planck researchers and their colleagues discuss the use of whole-genome shotgun sequencing and array-based sequence capture in interrogating the genomes of extinct organisms. The authors write that "hybridization capture on microarrays can successfully recover more than a megabase of target regions from Neandertal DNA even in the presence of ~99.8 percent microbial DNA." In this way, they sequenced the approximately 14,000 protein-coding positions "inferred to have changed on the human lineage since the last common ancestor shared with chimpanzees," and "identified 88 amino acid substitutions that have become fixed in humans since our divergence from the Neandertals."
In an advance, online publication of Science this week, geneticists at the Yale University School of Medicine and their colleagues report a Dicer-independent miRNA biogenesis pathway that uses Ago2 slicer catalytic activity — which they show is critical for pre-miR-451 processing in vivo. "Changing the secondary structure of dicer-dependent miRNAs to mimic that of pre-miR-451 restored miRNA function and rescued developmental defects in MZdicer mutants, indicating that the pre-miRNA secondary structure determines the processing pathway in vivo," the authors write, adding their suggestion that the Ago2-mediated cleavage of pre-miRNAs…generates functional miRNAs independently of Dicer."
An international research team reports that "altered histone acetylation is associated with age-dependent memory impairment in mice," in Science this week. Specifically, aged mice show a deregulation of histone H4 lysine 12 acetylation and, consequently, their hippocampal gene expression does not reflect a program associated with memory consolidation." Restoration of physiological H4K12 acetylation reinstates the expression of learning-induced genes and leads to the recovery of cognitive abilities," the team writes, adding that H4K12 could be a biomarker for "an impaired genome-environment interaction in the aging mouse brain."