P2y Receptor Structure

For this in mouse cells, but “we’ve been grasping to get a decade to seek out a mechanism in humans,” says coauthor Barry Bloom (Harvard School of Public Health, Boston, MA). The answer came from gene arrays. Active TLR turned on production of both an enzyme (which converts 25D3 into active vitamin D) and also the vitamin D receptor.Within a seminal book, Susumu Ohno argued that gene duplication plays an important function in evolutionary innovation [1]. He outlined 3 distinct PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/20138380 fates of retained duplicates that were later formalized by others (for reviews, see [2,3]). First, after a duplication event, one paralog may retain the ancestral function, whereas the other allele may be relieved from purifying selection, allowing it to develop a novel function (later called “neofunctionalization”). Second, different functions or regulatory patterns of an ancestral gene might be split over the different paralogs (later called “subfunctionalization” [4,5]). Third, duplication may preserve the ancestral function in both duplicates, thereby introducing redundancy and/or increasing activity of the gene (“gene dosage effect” [6]). Recent studies have shown that duplications occur frequently during evolution, and most experts agree that many evolutionaryPLOS Biology | www.plosbiology.orginnovations are linked to duplication [70]. A well-known example are crystallins, structural proteins that make up 60 of the protein in the Bax inhibitor peptide V5 biological activity lenses of vertebrate eyes. Interestingly, paralogs of many crystallins function as molecular chaperones or glycolytic enzymes. Studies suggest that on multiple occasions, an ancestral gene encoding a (structurally very stable) chaperone or enzyme was duplicated, with one paralog retaining the ancestral function and one being tuned as a lens crystallin that played a crucial function in the optimization of eyesight [11,12]. The molecular mechanisms and evolutionary forces that lead to the retention of duplicates plus the development of novel functions are still heavily debated, and many different models leading to Ohno’s three basic outcomes have been proposed (reviewed in [2,3,13,14]). Some more recent models blur the distinction between neo- and subfunctionalization [15]. Co-option models, for example, propose that a novel function does not developFunctional Innovation through Gene DuplicationAuthor SummaryDarwin’s theory of evolution is one of gradual change, yet evolution sometimes takes remarkable leaps. Such evolutionary innovations are often linked to gene duplication through one of 3 basic scenarios: an extra copy can increase protein levels, different ancestral subfunctions can be split over the copies and evolve distinct regulation, or one of the duplicates can develop a novel function. Although there are numerous examples for all these trajectories, the underlying molecular mechanisms remain obscure, mostly because the preduplication genes and proteins no longer exist. Here, we study a family of fungal metabolic enzymes that hydrolyze disaccharides, and that all originated from the same ancestral gene through repeated duplications. By resurrecting the ancient genes and proteins using high-confidence predictions from many fungal genome sequences available, we show that the very first preduplication enzyme was promiscuous, preferring maltose-like substrates but also showing trace activity towards isomaltose-like sugars. After duplication, specific mutations near the active site of one copy optimized the minor activity at the expense o.