1,834 research outputs found
Evolution favors protein mutational robustness in sufficiently large populations
BACKGROUND: An important question is whether evolution favors properties such
as mutational robustness or evolvability that do not directly benefit any
individual, but can influence the course of future evolution. Functionally
similar proteins can differ substantially in their robustness to mutations and
capacity to evolve new functions, but it has remained unclear whether any of
these differences might be due to evolutionary selection for these properties.
RESULTS: Here we use laboratory experiments to demonstrate that evolution
favors protein mutational robustness if the evolving population is sufficiently
large. We neutrally evolve cytochrome P450 proteins under identical selection
pressures and mutation rates in populations of different sizes, and show that
proteins from the larger and thus more polymorphic population tend towards
higher mutational robustness. Proteins from the larger population also evolve
greater stability, a biophysical property that is known to enhance both
mutational robustness and evolvability. The excess mutational robustness and
stability is well described by existing mathematical theories, and can be
quantitatively related to the way that the proteins occupy their neutral
network.
CONCLUSIONS: Our work is the first experimental demonstration of the general
tendency of evolution to favor mutational robustness and protein stability in
highly polymorphic populations. We suggest that this phenomenon may contribute
to the mutational robustness and evolvability of viruses and bacteria that
exist in large populations
Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response
Dramatic rise of mutators has been found to accompany adaptation of bacteria
in response to many kinds of stress. Two views on the evolutionary origin of
this phenomenon emerged: the pleiotropic hypothesis positing that it is a
byproduct of environmental stress or other specific stress response mechanisms
and the second order selection which states that mutators hitchhike to fixation
with unrelated beneficial alleles. Conventional population genetics models
could not fully resolve this controversy because they are based on certain
assumptions about fitness landscape. Here we address this problem using a
microscopic multiscale model, which couples physically realistic molecular
descriptions of proteins and their interactions with population genetics of
carrier organisms without assuming any a priori fitness landscape. We found
that both pleiotropy and second order selection play a crucial role at
different stages of adaptation: the supply of mutators is provided through
destabilization of error correction complexes or fluctuations of production
levels of prototypic mismatch repair proteins (pleiotropic effects), while rise
and fixation of mutators occur when there is a sufficient supply of beneficial
mutations in replication-controlling genes. This general mechanism assures a
robust and reliable adaptation of organisms to unforeseen challenges. This
study highlights physical principles underlying physical biological mechanisms
of stress response and adaptation
Bringing Molecules Back into Molecular Evolution
Much molecular-evolution research is concerned with sequence analysis. Yet these sequences represent real, three-dimensional molecules with complex structure and function. Here I highlight a growing trend in the field to incorporate molecular structure and function into computational molecular-evolution work. I consider three focus areas: reconstruction and analysis of past evolutionary events, such as phylogenetic inference or methods to infer selection pressures; development of toy models and simulations to identify fundamental principles of molecular evolution; and atom-level, highly realistic computational modeling of molecular structure and function aimed at making predictions about possible future evolutionary events
Estimating and projecting HIV prevalence and AIDS deaths in Tanzania using antenatal surveillance data
BACKGROUND: The Estimations and Projections Package (EPP 2005) for HIV/AIDS estimates and projects HIV prevalence, number of people living with HIV and new HIV infections and AIDS cases using antenatal clinic (ANC) surveillance data. The prevalence projection produced by EPP can be transferred to SPECTRUM, a demographic projectionmodel, to calculate the number of AIDS deaths. This paper presents estimates and projections of HIV prevalence, new cases of HIV infections and AIDS deaths in Tanzania between 2001 and 2010 using the EPP 2005 and SPECTRUM soft-wares on ANC data. METHODS: For this study we used; the 1985 â 2004 ANC data set, the 2005 UN population estimates for urban and rural adults, which is based on the 2002 population census, and results of the 2003 Tanzania HIV Indicator Survey. The ANC surveillance sites were categorized into urban and rural areas on the basis of the standard national definitions of urban and rural areas, which led to 40 urban and 35 rural clinic sites. The rural and urban epidemics were run independently by fitting the model to all data and on level fits. RESULTS: The national HIV prevalence increased from 0% in 1981 to a peak of 8.1% in 1995, and gradually decreased to 6.5% in 2004 which stabilized until 2010. The urban HIV epidemic increased from 0% in 1981 peaking at 12.6% in 1992 and leveled to between 10.9% and 11.8% from 2003 to 2010. The rural epidemic peaked in 1995 at 7.0% and gradually declined to 5.2% in 2004, and then stabilized at between 5.1% and 5.3% from 2005 to 2010. New infections are projected to rise steadily, resulting in 250,000 new cases in 2010. Deaths due to AIDS started in 1985 and rose steadily to reach 120,000 deaths in 2010, with more females dying than men. CONCLUSION: The fact that the number of new infections is projected to increase steadily to reach 250,000 per year in 2010 calls for more concerted efforts to combat the spread of HIV infection particularly in the rural areas where the infrastructure needed for prevention programmes such as counseling and testing, condom accessibility and AIDS information is less developed
Detection of Gamma-Ray Emission from the Starburst Galaxies M82 and NGC 253 with the Large Area Telescope on Fermi
We report the detection of high-energy gamma-ray emission from two starburst
galaxies using data obtained with the Large Area Telescope on board the Fermi
Gamma-ray Space Telescope. Steady point-like emission above 200 MeV has been
detected at significance levels of 6.8 sigma and 4.8 sigma respectively, from
sources positionally coincident with locations of the starburst galaxies M82
and NGC 253. The total fluxes of the sources are consistent with gamma-ray
emission originating from the interaction of cosmic rays with local
interstellar gas and radiation fields and constitute evidence for a link
between massive star formation and gamma-ray emission in star-forming galaxies.Comment: Submitted to ApJ Letter
Gene Promoter Evolution Targets the Center of the Human Protein Interaction Network
Assessing the contribution of promoters and coding sequences to gene evolution is an important step toward discovering the major genetic determinants of human evolution. Many specific examples have revealed the evolutionary importance of cis-regulatory regions. However, the relative contribution of regulatory and coding regions to the evolutionary process and whether systemic factors differentially influence their evolution remains unclear. To address these questions, we carried out an analysis at the genome scale to identify signatures of positive selection in human proximal promoters. Next, we examined whether genes with positively selected promoters (Prom+ genes) show systemic differences with respect to a set of genes with positively selected protein-coding regions (Cod+ genes). We found that the number of genes in each set was not significantly different (8.1% and 8.5%, respectively). Furthermore, a functional analysis showed that, in both cases, positive selection affects almost all biological processes and only a few genes of each group are located in enriched categories, indicating that promoters and coding regions are not evolutionarily specialized with respect to gene function. On the other hand, we show that the topology of the human protein network has a different influence on the molecular evolution of proximal promoters and coding regions. Notably, Prom+ genes have an unexpectedly high centrality when compared with a reference distribution (Pâ=â0.008, for Eigenvalue centrality). Moreover, the frequency of Prom+ genes increases from the periphery to the center of the protein network (Pâ=â0.02, for the logistic regression coefficient). This means that gene centrality does not constrain the evolution of proximal promoters, unlike the case with coding regions, and further indicates that the evolution of proximal promoters is more efficient in the center of the protein network than in the periphery. These results show that proximal promoters have had a systemic contribution to human evolution by increasing the participation of central genes in the evolutionary process
Fermi Gamma-ray Imaging of a Radio Galaxy
The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating
from the giant radio lobes of the radio galaxy Centaurus A. The resolved
gamma-ray image shows the lobes clearly separated from the central active
source. In contrast to all other active galaxies detected so far in high-energy
gamma-rays, the lobe flux constitutes a considerable portion (>1/2) of the
total source emission. The gamma-ray emission from the lobes is interpreted as
inverse Compton scattered relic radiation from the cosmic microwave background
(CMB), with additional contribution at higher energies from the
infrared-to-optical extragalactic background light (EBL). These measurements
provide gamma-ray constraints on the magnetic field and particle energy content
in radio galaxy lobes, and a promising method to probe the cosmic relic photon
fields.Comment: 27 pages, includes Supplementary Online Material; corresponding
authors: C.C. Cheung, Y. Fukazawa, J. Knodlseder, L. Stawar
Fermi Large Area Telescope observations of PSR J1836+5925
The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly
unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments
of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic
plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8
million years, a spindown luminosity of 1.1 erg s, and a
large off-peak emission component, making it quite unusual among the known
gamma-ray pulsar population. We present an analysis of one year of LAT data,
including an updated timing solution, detailed spectral results and a long-term
light curve showing no indication of variability. No evidence for a surrounding
pulsar wind nebula is seen and the spectral characteristics of the off-peak
emission indicate it is likely magnetospheric. Analysis of recent XMM
observations of the X-ray counterpart yields a detailed characterization of its
spectrum, which, like Geminga, is consistent with that of a neutron star
showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa
A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279
It is widely accepted that strong and variable radiation detected over all
accessible energy bands in a number of active galaxies arises from a
relativistic, Doppler-boosted jet pointing close to our line of sight. The size
of the emitting zone and the location of this region relative to the central
supermassive black hole are, however, poorly known, with estimates ranging from
light-hours to a light-year or more. Here we report the coincidence of a
gamma-ray flare with a dramatic change of optical polarization angle. This
provides evidence for co-spatiality of optical and gamma-ray emission regions
and indicates a highly ordered jet magnetic field. The results also require a
non-axisymmetric structure of the emission zone, implying a curved trajectory
for the emitting material within the jet, with the dissipation region located
at a considerable distance from the black hole, at about 10^5 gravitational
radii.Comment: Published in Nature issued on 18 February 2010. Corresponding
authors: Masaaki Hayashida and Greg Madejsk
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