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321.
Flagel SB Clark JJ Robinson TE Mayo L Czuj A Willuhn I Akers CA Clinton SM Phillips PE Akil H 《Nature》2011,469(7328):53-57
Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, becoming attractive and desirable incentive stimuli. However, whether a cue acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Thus, individuals vary in the degree to which cues bias choice and potentially promote maladaptive behaviour. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of stimulus-reward learning in which incentive salience is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behaviour. This work provides insight into the neurobiology of a form of stimulus-reward learning that confers increased susceptibility to disorders of impulse control. 相似文献
322.
Synthetic chromosome arms function in yeast and generate phenotypic diversity by design 总被引:1,自引:0,他引:1
Dymond JS Richardson SM Coombes CE Babatz T Muller H Annaluru N Blake WJ Schwerzmann JW Dai J Lindstrom DL Boeke AC Gottschling DE Chandrasegaran S Bader JS Boeke JD 《Nature》2011,477(7365):471-476
Recent advances in DNA synthesis technology have enabled the construction of novel genetic pathways and genomic elements, furthering our understanding of system-level phenomena. The ability to synthesize large segments of DNA allows the engineering of pathways and genomes according to arbitrary sets of design principles. Here we describe a synthetic yeast genome project, Sc2.0, and the first partially synthetic eukaryotic chromosomes, Saccharomyces cerevisiae chromosome synIXR, and semi-synVIL. We defined three design principles for a synthetic genome as follows: first, it should result in a (near) wild-type phenotype and fitness; second, it should lack destabilizing elements such as tRNA genes or transposons; and third, it should have genetic flexibility to facilitate future studies. The synthetic genome features several systemic modifications complying with the design principles, including an inducible evolution system, SCRaMbLE (synthetic chromosome rearrangement and modification by loxP-mediated evolution). We show the utility of SCRaMbLE as a novel method of combinatorial mutagenesis, capable of generating complex genotypes and a broad variety of phenotypes. When complete, the fully synthetic genome will allow massive restructuring of the yeast genome, and may open the door to a new type of combinatorial genetics based entirely on variations in gene content and copy number. 相似文献
323.
Cadwell K Liu JY Brown SL Miyoshi H Loh J Lennerz JK Kishi C Kc W Carrero JA Hunt S Stone CD Brunt EM Xavier RJ Sleckman BP Li E Mizushima N Stappenbeck TS Virgin HW 《Nature》2008,456(7219):259-263
324.
Sex and recombination are widespread, but explaining these phenomena has been one of the most difficult problems in evolutionary biology. Recombination is advantageous when different individuals in a population carry different advantageous alleles. By bringing together advantageous alleles onto the same chromosome, recombination speeds up the process of adaptation and opposes the fixation of harmful mutations by means of Muller's ratchet. Nevertheless, adaptive substitutions favour sex and recombination only if the rate of adaptive mutation is high, and Muller's ratchet operates only in small or asexual populations. Here, by tracking the fate of modifier alleles that alter the frequency of sex and recombination, we show that background selection against deleterious mutant alleles provides a stochastic advantage to sex and recombination that increases with population size. The advantage arises because, with low levels of recombination, selection at other loci severely reduces the effective population size and genetic variance in fitness at a focal locus (the Hill-Robertson effect), making a population less able to respond to selection and to rid itself of deleterious mutations. Sex and recombination reveal the hidden genetic variance in fitness by combining chromosomes of intermediate fitness to create chromosomes that are relatively free of (or are loaded with) deleterious mutations. This increase in genetic variance within finite populations improves the response to selection and generates a substantial advantage to sex and recombination that is fairly insensitive to the form of epistatic interactions between deleterious alleles. The mechanism supported by our results offers a robust and broadly applicable explanation for the evolutionary advantage of recombination and can explain the spread of costly sex. 相似文献
325.
Zody MC Garber M Adams DJ Sharpe T Harrow J Lupski JR Nicholson C Searle SM Wilming L Young SK Abouelleil A Allen NR Bi W Bloom T Borowsky ML Bugalter BE Butler J Chang JL Chen CK Cook A Corum B Cuomo CA de Jong PJ DeCaprio D Dewar K FitzGerald M Gilbert J Gibson R Gnerre S Goldstein S Grafham DV Grocock R Hafez N Hagopian DS Hart E Norman CH Humphray S Jaffe DB Jones M Kamal M Khodiyar VK LaButti K Laird G Lehoczky J Liu X Lokyitsang T Loveland J Lui A Macdonald P Major JE Matthews L Mauceli E 《Nature》2006,440(7087):1045-1049
Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome. 相似文献
326.
327.
Grenyer R Orme CD Jackson SF Thomas GH Davies RG Davies TJ Jones KE Olson VA Ridgely RS Rasmussen PC Ding TS Bennett PM Blackburn TM Gaston KJ Gittleman JL Owens IP 《Nature》2006,444(7115):93-96
Global conservation strategies commonly assume that different taxonomic groups show congruent geographical patterns of diversity, and that the distribution of extinction-prone species in one group can therefore act as a surrogate for vulnerable species in other groups when conservation decisions are being made. The validity of these assumptions remains unclear, however, because previous tests have been limited in both geographical and taxonomic extent. Here we use a database on the global distribution of 19,349 living bird, mammal and amphibian species to show that, although the distribution of overall species richness is very similar among these groups, congruence in the distribution of rare and threatened species is markedly lower. Congruence is especially low among the very rarest species. Cross-taxon congruence is also highly scale dependent, being particularly low at the finer spatial resolutions relevant to real protected areas. 'Hotspots' of rarity and threat are therefore largely non-overlapping across groups, as are areas chosen to maximize species complementarity. Overall, our results indicate that 'silver-bullet' conservation strategies alone will not deliver efficient conservation solutions. Instead, priority areas for biodiversity conservation must be based on high-resolution data from multiple taxa. 相似文献