@article{17725, abstract = {A bright quasar residing in a dense and largely neutral intergalactic medium (IGM) at high redshifts (z > 6) will be surrounded by a large cosmological Stromgren sphere. The quasar's spectrum will then show a sharp increase in resonant Lyman line absorption at wavelengths approaching and shorter than that corresponding to the Stromgren sphere's boundary along the line of sight. We show here that simultaneously considering the measured absorption in two or more hydrogen Lyman lines can provide the dynamical range required to detect this feature. We model broad and robust features of the Lyman alpha and Lyman beta regions of the spectrum of the z=6.28 quasar SDSS J1030+0524, using a hydrodynamical simulation. From the steep wavelength-dependence of the inferred absorption opacity, we detect the boundary of the Stromgren sphere at a proper distance of 6.0 +/- 0.2 Mpc away from the source redshift. From the spectrum alone, we also find that beyond this distance, cosmic hydrogen turns nearly neutral, with a neutral fraction of x_HI > 0.2, and that the ionizing luminosity of this quasar is in the range (5.2 +/- 2.5) times 10^{56} photons/sec. The method presented here, when applied to future quasars, can probe the complex topology of overlapping ionized regions, and can be used to study the details of the reionization process.}, author = {Mesinger, Andrei and Haiman, Zoltán}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {2}, pages = {L69--L72}, publisher = {American Astronomical Society}, title = {{Evidence of a cosmological Strömgren surface and of significant neutral hydrogen surrounding the quasar SDSS J1030+0524}}, doi = {10.1086/423935}, volume = {611}, year = {2004}, } @article{17726, abstract = {We present deep unbiased spectroscopy of the Hubble Ultra Deep Field (UDF) carried out using the slitless grism spectroscopy mode of the Advance Camera for Surveys on the Hubble Space Telescope (HST). The GRIsm ACS Program for Extragalactic Science (GRAPES) achieves continuum detection as faint as zAB=27.2 using 40 orbits (9.2×10^4 seconds) on HST. The data were taken at four orientation angles to correct for the overlap of spectra. GRAPES data provide a unique, uninterrupted, low resolution (R=100) spectral coverage for 5500Å<λ<10500Å, and allow us to detect high redshift galaxies at 410). We find that the importance of photoionization feedback is greatly reduced, because (1) at high redshift, dwarf-galaxy sized objects can self-shield against the ionizing background, (2) collisional cooling processes at high redshift are more efficient, (3) the amplitude of the ionizing background at high redshift is lower, and (4) the ionizing radiation turns on when the perturbation that will become the dwarf galaxy has already grown to a substantial overdensity. We find that because of these reasons, gas can collect inside halos with circular velocities as low as v(circ)=10 km/s. This result has important implications for the reionization history of the universe.}, author = {Dijkstra, Mark and Haiman, Zoltán and Rees, Martin J. and Weinberg, David H.}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {2}, pages = {666--675}, publisher = {American Astronomical Society}, title = {{Photoionization feedback in low‐mass galaxies at high redshift}}, doi = {10.1086/380603}, volume = {601}, year = {2004}, } @article{17743, abstract = {We use a physically motivated semi-analytic model, based on the mass function of dark matter halos, to predict the number of radio-loud quasars as a function of redshift and luminosity. Simple models in which the central BH mass scales with the velocity dispersion of its host halo as M(bh) sigma(halo)^5 have been previously found to be consistent with a number of observations, including the optical and X-ray quasar luminosity functions. We find that similar models, when augmented with an empirical prescription for radio emission, overpredict the number of faint (10 micro-Jy) radio sources by 1-2 orders of magnitude. This translates into a more stringent constraint on the low-mass end of the quasar black hole mass function than is available from the Hubble and Chandra Deep Fields. We interpret this discrepancy as evidence that black holes with masses below 10^7 Msun are either rare or are not as radio-loud as their more massive counterparts. Models that exclude BHs with masses below 10^7 Msun are in agreement with the deepest existing radio observations, but still produce a significant tail of high-redshift objects. In the 1-10GHz bands, at the sensitivity of 10 micro-Jy, we find surface densities of 100, 10, and 0.3 deg^-2 for sources located at z>6, 10, and 15, respectively. The discovery of these sources with instruments such as the Allen Telescope Array (ATA), Extended Very Large Array (EVLA), and the Square Kilometer Array (SKA) would open a new window for the study of supermassive BHs at high redshift. We also find surface densities of 0.1 deg^-2 at z > 6 for mJy sources that can be used to study 21 cm absorption from the epoch of reionization. We suggest that, although not yet optically identified, the FIRST survey may have already detected 10^3-10^4 such sources.}, author = {Haiman, Zoltán and Quataert, Eliot and Bower, Geoffrey C.}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {2}, pages = {698--705}, publisher = {American Astronomical Society}, title = {{Modeling the counts of faint radio‐loud quasars: Constraints on the supermassive black hole population and predictions for high redshift}}, doi = {10.1086/422834}, volume = {612}, year = {2004}, } @article{17745, abstract = {We quantify and discuss the footprints of neutral hydrogen in the intergalactic medium (IGM) on the spectra of high-redshift (z ~ 6) sources, using mock spectra generated from hydrodynamical simulations of the IGM. We show that it should be possible to extract relevant parameters, including the mean neutral fraction in the IGM and the radius of the local cosmological Strömgren region, from the flux distribution in the observed spectra of distant sources. We focus on quasars, but a similar analysis is applicable to galaxies and gamma-ray burst (GRB) afterglows. We explicitly include uncertainties in the spectral shape of the assumed source template near the Lyα line. Our results suggest that a mean neutral hydrogen fraction, xH, of unity can be statistically distinguished from xH ≈ 10^-2 by combining the spectra of tens of bright (M ≈ -27) quasars. Alternatively, the same distinction can be achieved using the spectra of several hundred sources that are ~100 times fainter. Furthermore, if the radius of the Strömgren sphere can be independently constrained to within ~10%, this distinction can be achieved using a single source. The information derived from such spectra will help in settling the current debate as to what extent the universe was reionized at redshifts near z ~ 6.}, author = {Mesinger, Andrei and Haiman, Zoltán and Cen, Renyue}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {1}, pages = {23--35}, publisher = {American Astronomical Society}, title = {{Probing the reionization history using the spectra of high‐redshift sources}}, doi = {10.1086/422898}, volume = {613}, year = {2004}, } @inproceedings{17747, abstract = {Dark Energy dominates the mass-energy content of the universe (about 73%) but we do not understand it. Most of the remainder of the Universe consists of Dark Matter (23%), made of an unknown particle. The problem of the origin of Dark Energy has become the biggest problem in astrophysics and one of the biggest problems in all of science. The major extant X-ray observatories, the Chandra X-ray Observatory and XMM-Newton, do not have the ability to perform large-area surveys of the sky. But Dark Energy is smoothly distributed throughout the universe and the whole universe is needed to study it. There are two basic methods to explore the properties of Dark Energy, viz. geometrical tests (supernovae) and studies of the way in which Dark Energy has influenced the large scale structure of the universe and its evolution. DUO will use the latter method, employing the copious X-ray emission from clusters of galaxies. Clusters of galaxies offer an ideal probe of cosmology because they are the best tracers of Dark Matter and their distribution on very large scales is dominated by the Dark Energy. In order to take the next step in understanding Dark Energy, viz. the measurement of the 'equation of state' parameter 'w', an X-ray telescope following the design of ABRIXAS will be accommodated into a Small Explorer mission in lowearth orbit. The telescope will perform a scan of 6,000 sq. degs. in the area of sky covered by the Sloan Digital Sky Survey (North), together with a deeper, smaller survey in the Southern hemisphere. DUO will detect 10.000 clusters of galaxies, measure the number density of clusters as a function of cosmic time, and the power spectrum of density fluctuations out to a redshift exceeding one. When combined with the spectrum of density fluctuations in the Cosmic Microwave Background from a redshift of 1100, this will provide a powerful lever arm for the crucial measurement of cosmological parameters.}, author = {Griffiths, Richard and Petre, Robert and Hasinger, Guenther and Predehl, Peter and White, Nicholas E. and Aschenbach, Bernd and Barcons, Xavier and Bohringer, Hans and Briel, Ulrich G. and Cominsky, Lynn and Corcoran, Michael F. and Dinger, Udo and Egle, Wilhelm J. and Friedrich, Peter and Haiman, Zoltán and Hartmann, Robert and Henry, J. Patrick and Hippmann, Horst and Ingersoll, Jim and Jahoda, Keith and Jenstrom, Del T. and Jordan, Steven and Kendziorra, Eckhard and Kettenring, G’nther and Kink, Walter and Meidinger, Norbert and Miyaji, Takamitsu and Mohr, Joseph and Mueller, Siegfried and Mushotzky, Richard F. and Pfeffermann, Elmar and Schuecker, Peter and Schwope, Axel and Shannon, Mark and Strueder, Lothar and Varlese, Steven J.}, booktitle = {SPIE Astronomical Telescopes + Instrumentation}, editor = {Hasinger, Guenther and Turner, Martin J. L.}, issn = {0277-786X}, location = {Glasgow, United Kingdom}, publisher = {SPIE}, title = {{DUO: The dark universe observatory}}, doi = {10.1117/12.552171}, volume = {5488}, year = {2004}, } @article{17758, abstract = {Krstic has carried out the first quantum mechanical calculations near threshold for the charge transfer (CT) process H^+ + H_2(X ^1Sigma_g^+, nu=0, J=0) --> H(1s) + H_2^+. These results are relevant for models of primordial galaxy and first star formation that require reliable atomic and molecular data for obtaining the early universe hydrogen chemistry. Using the results of Krstic, we calculate the relevant CT rate coefficient for temperatures between 100 and 30,000 K. We also present a simple fit which can be readily implemented into early universe chemical models. Additionally, we explore how the range of previously published data for this reaction translates into uncertainties in the predicted gas temperature and H_2 relative abundance in a collapsing primordial gas cloud. Our new data significantly reduce these cosmological uncertainties that are due to the uncertainties in the previously published CT rate coefficients.}, author = {Savin, Daniel Wolf and Krsti, Predrag S. and Haiman, Zoltán and Stancil, Phillip C.}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {2}, pages = {L167--L170}, publisher = {American Astronomical Society}, title = {{Rate Coefficient for H+ + H2(X1Σg+, ν = 0, J = 0) → H(1s) + H2+ Charge Transfer and Some Cosmological Implications}}, doi = {10.1086/421108}, volume = {606}, year = {2004}, } @article{17763, abstract = {Recent studies have suggested that during their coalescence, binary supermassive black holes (SMBHs) experience typical gravitational recoil velocities that may be as large as ≳100 km s^-1. These velocities exceed the escape velocity vesc from typical dark matter (DM) halos at high redshift (z ≳ 6), and therefore put constraints on scenarios in which early SMBHs grow at the centers of DM halos. Here we quantify these constraints for the most distant known SMBH, with an inferred mass in excess of 10^9 M☉, powering the bright quasar SDSS J1148+5251 discovered in the Sloan Digital Sky Survey at z = 6.43. We assume that this SMBH grew via a combination of accretion and mergers between preexisting seed BHs in individual progenitor halos, and that mergers between progenitors with vesc < vkick disrupt the BH growth process. Our results suggest that under these assumptions, the z ≈ 6 SMBHs had a phase during which they gained mass vary rapidly. In particular, typical z ≈ 3 quasars with luminosities similar to that of SDSS J1148+5251 have recently been inferred to have an average radiative efficiency of epsilon ≈ 20%. The growth rate of the SMBH in SDSS J1148+5251 must have significantly exceeded the Eddington accretion rate with this efficiency.}, author = {Haiman, Zoltán}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {1}, pages = {36--40}, publisher = {American Astronomical Society}, title = {{Constraints from gravitational recoil on the growth of supermassive black holes at high redshift}}, doi = {10.1086/422910}, volume = {613}, year = {2004}, } @article{17770, abstract = {We show that the abundance and redshift distribution (𝑑⁢𝑁/𝑑⁢𝑧) of galaxy clusters in future high-yield cluster surveys, combined with the spatial power spectrum [𝑃𝑐⁡(𝑘)] of the same clusters, can place significant constraints on the evolution of the dark energy equation of state, 𝑤=𝑤⁡(𝑎). We evaluate the expected errors on 𝑤𝑎=−𝑑⁢𝑤/𝑑⁢𝑎 and other cosmological parameters using a Fisher matrix approach, and simultaneously including cluster structure evolution parameters in our analysis. We study three different types of forthcoming surveys that will identify clusters based on their x-ray emission (such as DUO, the Dark Universe Observatory), their Sunyaev-Zel'dovich (SZ) decrement (such as SPT, the South Pole Telescope), or their weak-lensing shear (such as LSST, the Large Synoptic Survey Telescope). We find that combining the cluster abundance and power spectrum significantly enhances constraints from either method alone. We show that the weak-lensing survey can deliver a constraint as tight as 𝛥⁢𝑤𝑎∼0.1 on the evolution of the dark energy equation of state, and that the x-ray and SZ surveys each yield 𝛥⁢𝑤𝑎∼0.4 separately, or 𝛥⁢𝑤𝑎∼0.2 when these two surveys are combined. For the x-ray and SZ surveys, constraints on dark energy parameters are improved by a factor of 2 by combining the cluster data with cosmic microwave background anisotropy measurements by Planck, but degrade by a factor of 2 if the survey is required to solve simultaneously for cosmological and cluster structure evolution parameters. The constraint on 𝑤𝑎 from the weak-lensing survey is improved by ∼25% with the addition of Planck data.}, author = {Wang, Sheng and Khoury, Justin and Haiman, Zoltán and May, Morgan}, issn = {1550-7998}, journal = {Physical Review D}, number = {12}, publisher = {American Physical Society}, title = {{Constraining the evolution of dark energy with a combination of galaxy cluster observables}}, doi = {10.1103/physrevd.70.123008}, volume = {70}, year = {2004}, } @article{17775, abstract = {We discuss a simple model for the growth of supermassive black holes (BHs) at the center of spheroidal stellar systems. In particular, we assess the hypotheses that (1) star formation in spheroids and BH fueling are proportional to one another, and (2) the BH accretion luminosity stays near the Eddington limit during luminous quasar phases. With the aid of this simple model, we are able to interpret many properties of the QSO luminosity function, including the puzzling steep decline of the characteristic luminosity from redshift z=2 to to z=0: indeed the residual star formation in spheroidal systems is today limited to a small number of bulges, characterized by stellar velocity dispersions a factor of 2-3 smaller those of the elliptical galaxies hosting QSOs at z > 2. A simple consequence of our hypotheses is that the redshift evolution of the QSO emissivity and of the star formation history in spheroids should be roughly parallel. We find this result to be broadly consistent with our knowledge of the evolution of both the global star formation rate, and of the evolution of the QSO emissivity, but we identify interesting discrepancies at both low and high redshifts, to which we offer tentative solutions. Finally, our hypotheses allow us to present a robust method to derive the duty cycle of QSO activity, based on the observed QSO luminosity function, and on the present-day relation between the masses of supermassive BHs and those of their spheroidal host stellar systems. The duty cycle is found to be substantially less than unity, with characteristic values in the range (3-6)x10^(-3), and we compute that the average bolometric radiative efficiency is epsilon=0.07. Finally, we find that the growth in mass of individual black holes at high redshift (z>2) can be dominated by mergers, and is therefore not necessarily limited by accretion.}, author = {Haiman, Zoltán and Ciotti, Luca and Ostriker, Jeremiah P.}, issn = {0004-637X}, journal = {The Astrophysical Journal}, number = {2}, pages = {763--773}, publisher = {American Astronomical Society}, title = {{Reasoning from fossils: Learning from the local black hole population about the evolution of quasars}}, doi = {10.1086/383022}, volume = {606}, year = {2004}, } @article{17790, abstract = {Over the last few years, the Sloan Digital Sky Survey (SDSS) has discovered several hundred quasars with redshift between 4.0 and 6.4. Including the effects of magnification bias, one expects a priori that an appreciable fraction of these objects are gravitationally lensed. We have used the Advanced Camera for Surveys on the Hubble Space Telescope to carry out a snapshot imaging survey of high-redshift SDSS quasars to search for gravitationally split lenses. This paper, the first in a series reporting the results of the survey, describes snapshot observations of four quasars at z = 5.74, 5.82, 5.99, and 6.30, respectively. We find that none of these objects has a lensed companion within 5 mag with a separation larger than 0farcs3; within 2.5 mag we can rule out companions within 0farcs1. Based on the nondetection of strong lensing in these four systems, we constrain the z ∼ 6 luminosity function to a slope of β > -4.63 (3 σ), assuming a break in the quasar luminosity function at M = -24.1. We discuss the implications of this constraint on the ionizing background due to quasars in the early universe. Given that these quasars are not highly magnified, estimates of the masses of their central engines by the Eddington argument must be taken seriously, possibly challenging models of black hole formation.}, author = {Richards, Gordon T. and Strauss, Michael A. and Pindor, Bartosz and Haiman, Zoltán and Fan, Xiaohui and Eisenstein, Daniel and Schneider, Donald P. and Bahcall, Neta A. and Brinkmann, J. and Brunner, Robert}, issn = {0004-6256}, journal = {The Astronomical Journal}, number = {3}, pages = {1305--1312}, publisher = {American Astronomical Society}, title = {{A snapshot survey for gravitational lenses among z ≥ 4.0 quasars. I. The z >5.7 sample}}, doi = {10.1086/381906}, volume = {127}, year = {2004}, } @article{17792, abstract = {Which came first, the stars and gas that make up a galaxy, or the giant black hole at its centre? Observations of a distant galaxy, caught as it forms, could help solve this chicken-and-egg problem.}, author = {Haiman, Zoltán}, issn = {0028-0836}, journal = {Nature}, number = {7003}, pages = {979--980}, publisher = {Springer Science and Business Media LLC}, title = {{Caught in the act?}}, doi = {10.1038/430979a}, volume = {430}, year = {2004}, } @article{17806, abstract = {A population of black holes (BHs) at high redshifts (z ≳ 6) that contributes significantly to the ionization of the intergalactic medium (IGM) would be accompanied by the copious production of hard (≳10 keV) X-ray photons. The resulting hard X-ray background would redshift and be observed as a present-day soft X-ray background (SXB). Under the hypothesis that BHs are the main producers of reionizing photons in the high-redshift universe, we calculate their contribution to the present-day SXB. We find that accreting BHs with a hard spectrum (be it luminous quasars or their lower mass "miniquasar" counterparts) could not fully reionize the universe without saturating the unresolved component of the 0.5-2 keV SXB at the ≥2 σ level. Distant miniquasars that produce enough X-rays to only partially ionize the IGM to a level of at most xe ~ 50% saturate the unresolved SXB by ≲1 σ. Improved determinations of the unresolved component of the SXB can provide a powerful constraint on the contribution of accreting BHs to partial or full reionization.}, author = {Dijkstra, Mark and Haiman, Zoltán and Loeb, Abraham}, issn = {1538-4357}, journal = {The Astrophysical Journal}, number = {2}, pages = {646--654}, publisher = {American Astronomical Society}, title = {{A limit from the X‐ray background on the contribution of quasars to reionization}}, doi = {10.1086/422167}, volume = {613}, year = {2004}, } @article{7706, abstract = {The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.}, author = {Brunet, Anne and Sweeney, Lora Beatrice Jaeger and Sturgill, J Fitzhugh and Chua, Katrin and Greer, Paul and Lin, Yingxi and Tran, Hien and Ross, Sarah and Mostoslavsky, Raul and Cohen, Haim and Hu, Linda and Chen, Hwei-Ling and Jedrychowski, Mark and Gygi, Steven and Sinclair, David and Alt, Frederick and Greenberg, Michael}, issn = {0036-8075}, journal = {Science}, number = {5666}, pages = {2011--2015}, publisher = {American Association for the Advancement of Science}, title = {{Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase}}, doi = {10.1126/science.1094637}, volume = {303}, year = {2004}, } @article{8517, abstract = {We consider the evolution of a connected set on the plane carried by a space periodic incompressible stochastic flow. While for almost every realization of the stochastic flow at time t most of the particles are at a distance of order equation image away from the origin, there is a measure zero set of points that escape to infinity at the linear rate. We study the set of points visited by the original set by time t and show that such a set, when scaled down by the factor of t, has a limiting nonrandom shape.}, author = {Dolgopyat, Dmitry and Kaloshin, Vadim and Koralov, Leonid}, issn = {0010-3640}, journal = {Communications on Pure and Applied Mathematics}, keywords = {Applied Mathematics, General Mathematics}, number = {9}, pages = {1127--1158}, publisher = {Wiley}, title = {{A limit shape theorem for periodic stochastic dispersion}}, doi = {10.1002/cpa.20032}, volume = {57}, year = {2004}, } @article{8518, author = {Koralov, Leonid and Kaloshin, Vadim and Dolgopyat, Dmitry}, issn = {0091-1798}, journal = {The Annals of Probability}, number = {1A}, pages = {1--27}, publisher = {Institute of Mathematical Statistics}, title = {{Sample path properties of the stochastic flows}}, doi = {10.1214/aop/1078415827}, volume = {32}, year = {2004}, } @article{864, abstract = {We present a method for prediction of functional sites in a set of aligned protein sequences. The method selects sites which are both well conserved and clustered together in space, as inferred from the 3D structures of proteins included in the alignment. We tested the method using 86 alignments from the NCBI CDD database, where the sites of experimentally determined ligand and/or macromolecular interactions are annotated. In agreement with earlier investigations, we found that functional site predictions are most successful when overall background sequence conservation is low, such that sites under evolutionary constraint become apparent. In addition, we found that averaging of conservation values across spatially clustered sites improves predictions under certain conditions: that is, when overall conservation is relatively high and when the site in question involves a large macromolecular binding interface. Under these conditions it is better to look for clusters of conserved sites than to look for particular conserved sites.}, author = {Panchenko, Anna R and Fyodor Kondrashov and Bryant, Stephen H}, journal = {Protein Science}, number = {4}, pages = {884 -- 892}, publisher = {Wiley-Blackwell}, title = {{Prediction of functional sites by analysis of sequence and structure conservation}}, doi = {10.1110/ps.03465504}, volume = {13}, year = {2004}, } @article{870, abstract = {Only a fraction of eukaryotic genes affect the phenotype drastically. We compared 18 parameters in 1273 human morbid genes, known to cause diseases, and in the remaining 16 580 unambiguous human genes. Morbid genes evolve more slowly, have wider phylogenetic distributions, are more similar to essential genes of Drosophila melanogaster, code for longer proteins containing more alanine and glycine and less histidine, lysine and methionine, possess larger numbers of longer introns with more accurate splicing signals and have higher and broader expressions. These differences make it possible to classify as non-morbid 34% of human genes with unknown morbidity, when only 5% of known morbid genes are incorrectly classified as non-morbid. This classification can help to identify disease-causing genes among multiple candidates.}, author = {Fyodor Kondrashov and Ogurtsov, Aleksey Yu and Kondrashov, Alexey S}, journal = {Nucleic Acids Research}, number = {5}, pages = {1731 -- 1737}, publisher = {Oxford University Press}, title = {{Bioinformatical assay of human gene morbidity}}, doi = {10.1093/nar/gkh330}, volume = {32}, year = {2004}, } @article{875, abstract = {The dominance of wild-type alleles and the concomitant recessivity of deleterious mutant alleles might have evolved by natural selection or could be a by-product of the molecular and physiological mechanisms of gene action. We compared the properties of human haplosufficient genes, whose wild-type alleles are dominant over loss-of-function alleles, with haploinsufficient (recessive wild-type) genes, which produce an abnormal phenotype when heterozygous for a loss-of-function allele. The fraction of haplosufficient genes is the highest among the genes that encode enzymes, which is best compatible with the physiological theory. Haploinsufficient genes, on average, have more paralogs than haplosufficient genes, supporting the idea that gene dosage could be important for the initial fixation of duplications. Thus, haplo(in)sufficiency of a gene and its propensity for duplication might have a common evolutionary basis.}, author = {Fyodor Kondrashov and Koonin, Eugene V}, journal = {Trends in Genetics}, number = {7}, pages = {287 -- 291}, publisher = {Elsevier}, title = {{A common framework for understanding the origin of genetic dominance and evolutionary fates of gene duplications}}, doi = {10.1016/j.tig.2004.05.001}, volume = {20}, year = {2004}, } @article{889, abstract = {The function of protein and RNA molecules depends on complex epistatic interactions between sites. Therefore, the deleterious effect of a mutation can be suppressed by a compensatory second-site substitution. In relating a list of 86 pathogenic mutations in human IRNAs encoded by mitochondrial genes to the sequences of their mammalian orthologs, we noted that 52 pathogenic mutations were present in normal tRNAs of one or several nonhuman mammals. We found at least five mechanisms of compensation for 32 pathogenic mutations that destroyed a Watson-Crick pair in one of the four tRNA stems: restoration of the affected Watson-Crick interaction (25 cases), strengthening of another pair (4 cases), creation of a new pair (8 cases), changes of multiple interactions in the affected stem (11 cases) and changes involving the interaction between the loop and stem structures (3 cases). A pathogenic mutation and its compensating substitution are fixed in a lineage in rapid succession, and often a compensatory interaction evolves convergently in different clades. At least 10%, and perhaps as many as 50%, of all nucleotide substitutions in evolving mammalian (RNAs participate in such interactions, indicating that the evolution of tRNAs proceeds along highly epistatic fitness ridges.}, author = {Kern, Andrew D and Fyodor Kondrashov}, journal = {Nature Genetics}, number = {11}, pages = {1207 -- 1212}, publisher = {Nature Publishing Group}, title = {{Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs}}, doi = {10.1038/ng1451}, volume = {36}, year = {2004}, }