Limited Evidence for Parallel Evolution Among Desert-Adapted Peromyscus Deer Mice

Warming climate and increasing desertification urge the identification of genes involved in heat and dehydration tolerance to better inform and target biodiversity conservation efforts. Comparisons among extant desert-adapted species can highlight parallel or convergent patterns of genome evolution through the identification of shared signatures of selection. We generate a chromosome-level genome assembly for the canyon mouse (Peromyscus crinitus) and test for a signature of parallel evolution by comparing signatures of selective sweeps across population-level genomic resequencing data from another congeneric desert specialist (Peromyscus eremicus) and a widely distributed habitat generalist (Peromyscus maniculatus), that may be locally adapted to arid conditions. We identify few shared candidate loci involved in desert adaptation and do not find support for a shared pattern of parallel evolution. Instead, we hypothesize divergent molecular mechanisms of desert adaptation among deer mice, potentially tied to species-specific historical demography, which may limit or enhance adaptation. We identify a number of candidate loci experiencing selective sweeps in the P. crinitus genome that are implicated in osmoregulation (Trypsin, Prostasin) and metabolic tuning (Kallikrein, eIF2-alpha kinase GCN2, APPL1/2), which may be important for accommodating hot and dry environmental conditions

A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping

SummaryWe use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs “facing” one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.PaperFlic

Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes

We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic “tension globule.” In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.National Science Foundation (U.S.) (Grant PHY-1427654)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD008540-01)Cancer Prevention and Research Institute of Texas (Scholar Award R1304)Baylor College of Medicine (McNair Medical Institute Scholar Award)Presidential Early Career Award for Scientists and Engineer

A new dynamical model for the black hole binary LMC X-1

We present a dynamical model of the high mass X-ray binary LMC X-1 based on high-resolution optical spectroscopy and extensive optical and near-infrared photometry. From our new optical data we find an orbital period of P = 3.90917 +/- 0.00005 days. We present a refined analysis of the All Sky Monitor data from RXTE and find an X-ray period of P = 3.9094 +/- 0.0008 days, which is consistent with the optical period. A simple model of Thomson scattering in the stellar wind can account for the modulation seen in the X-ray light curves. The V-K color of the star (1.17 +/- 0.05) implies A(V) = 2.28 +/- 0.06, which is much larger than previously assumed. For the secondary star, we measure a radius of R-2 = 17.0 +/- 0.8 R-circle dot and a projected rotational velocity of V-rot sin i = 129.9 +/- 2.2 km s(-1). Using these measured properties to constrain the dynamical model, we find an inclination of i = 36 degrees.38 +/- 1 degrees.92, a secondary star mass of M-2 = 31.79 +/- 3.48 M-circle dot, and a black hole mass of 10.91 +/- 1.41 M-circle dot. The present location of the secondary star in a temperature-luminosity diagram is consistent with that of a star with an initial mass of 35 M-circle dot that is 5 Myr past the zero-age main sequence. The star nearly fills its Roche lobe (approximate to 90% or more), and owing to the rapid change in radius with time in its present evolutionary state, it will encounter its Roche lobe and begin rapid and possibly unstable mass transfer on a timescale of a few hundred thousand years

A New Dynamical Model for the Black Hole Binary Lmc X-1

We present a dynamical model of the high mass X-ray binary LMC X-1 based on high-resolution optical spectroscopy and extensive optical and nearinfrared photometry. From our new optical data we find an orbital period of P = 3.90917±0.00005 days. We present a refined analysis of the All Sky Monitor data from RXTE and find an X-ray period of P = 3.9094±0.0008 days, which is consistent with the optical period. A simple model of Thomson scattering in the stellar wind can account for the modulation seen in the X-ray light curves. The V − K color of the star (1.17 ± 0.05) implies AV = 2.28 ± 0.06, which is much larger than previously assumed. For the secondary star, we measure a radius of R2 = 17.0±0.8 R⊙ and a projected rotational velocity of Vrot sin i = 129.9±2.2 km s −1 . Using these measured properties to constrain the dynamical model, we find an inclination of i = 36.38±1.92◦ , a secondary star mass of M2 = 31.79±3.48 M⊙, and a black hole mass of 10.91 ± 1.41 M⊙. The present location of the secondary star in a temperature-luminosity diagram is consistent with that of a star with an initial mass of 35 M⊙ that is 5 Myr past the zero-age main sequence. The star nearly fills its Roche lobe (≈ 90% or more), and owing to the rapid change in radius with time in its present evolutionary state, it will encounter its Roche lobe and begin rapid and possibly unstable mass transfer on a timescale of a few hundred thousand years.Astronom

Cohesin Loss Eliminates All Loop Domains

The human genome folds to create thousands of intervals, called “contact domains,” that exhibit enhanced contact frequency within themselves. “Loop domains” form because of tethering between two loci—almost always bound by CTCF and cohesin—lying on the same chromosome. “Compartment domains” form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid. Mapping the nucleome in 4D during cohesin loss and recovery reveals that cohesin degradation eliminates loop domains but has only modest transcriptional consequences. Keywords: cohesion; genome architecture; loop extrusion; chromatin loops; superenhancers; gene regulation; nuclear compartments; Hi-C; 4D Nucleome; CTC