The inflated significance of neutral genetic diversity in conservation genetics

The current rate of species extinction is rapidly approaching unprecedented highs, and life on Earth presently faces a sixth mass extinction event driven by anthropogenic activity, climate change, and ecological collapse. The field of conservation genetics aims at preserving species by using their levels of genetic diversity, usually measured as neutral genome-wide diversity, as a barometer for evaluating population health and extinction risk. A fundamental assumption is that higher levels of genetic diversity lead to an increase in fitness and long-term survival of a species. Here, we argue against the perceived importance of neutral genetic diversity for the conservation of wild populations and species. We demonstrate that no simple general relationship exists between neutral genetic diversity and the risk of species extinction. Instead, a better understanding of the properties of functional genetic diversity, demographic history, and ecological relationships is necessary for developing and implementing effective conservation genetic strategies.João C. Teixeira and Christian D. Hube

Determining the effect of natural selection on linked neutral divergence across species

A major goal in evolutionary biology is to understand how natural selection has shaped patterns of genetic variation across genomes. Studies in a variety of species have shown that neutral genetic diversity (intra-species differences) has been reduced at sites linked to those under direct selection. However, the effect of linked selection on neutral sequence divergence (inter-species differences) remains ambiguous. While empirical studies have reported correlations between divergence and recombination, which is interpreted as evidence for natural selection reducing linked neutral divergence, theory argues otherwise, especially for species that have diverged long ago. Here we address these outstanding issues by examining whether natural selection can affect divergence between both closely and distantly related species. We show that neutral divergence between closely related species (e.g. human-primate) is negatively correlated with functional content and positively correlated with human recombination rate. We also find that neutral divergence between distantly related species (e.g. human-rodent) is negatively correlated with functional content and positively correlated with estimates of background selection from primates. These patterns persist after accounting for the confounding factors of hypermutable CpG sites, GC content, and biased gene conversion. Coalescent models indicate that even when the contribution of ancestral polymorphism to divergence is small, background selection in the ancestral population can still explain a large proportion of the variance in divergence across the genome, generating the observed correlations. Our findings reveal that, contrary to previous intuition, natural selection can indirectly affect linked neutral divergence between both closely and distantly related species. Though we cannot formally exclude the possibility that the direct effects of purifying selection drive some of these patterns, such a scenario would be possible only if more of the genome is under purifying selection than currently believed. Our work has implications for understanding the evolution of genomes and interpreting patterns of genetic variation.Tanya N. Phung, Christian D. Huber, Kirk E. Lohmuelle

Deleterious variation shapes the genomic landscape of introgression

While it is appreciated that population size changes can impact patterns of deleterious variation in natural populations, less attention has been paid to how gene flow affects and is affected by the dynamics of deleterious variation. Here we use population genetic simulations to examine how gene flow impacts deleterious variation under a variety of demographic scenarios, mating systems, dominance coefficients, and recombination rates. Our results show that admixture between populations can temporarily reduce the genetic load of smaller populations and cause increases in the frequency of introgressed ancestry, especially if deleterious mutations are recessive. Additionally, when fitness effects of new mutations are recessive, between-population differences in the sites at which deleterious variants exist creates heterosis in hybrid individuals. Together, these factors lead to an increase in introgressed ancestry, particularly when recombination rates are low. Under certain scenarios, introgressed ancestry can increase from an initial frequency of 5% to 30-75% and fix at many loci, even in the absence of beneficial mutations. Further, deleterious variation and admixture can generate correlations between the frequency of introgressed ancestry and recombination rate or exon density, even in the absence of other types of selection. The direction of these correlations is determined by the specific demography and whether mutations are additive or recessive. Therefore, it is essential that null models of admixture include both demography and deleterious variation before invoking other mechanisms to explain unusual patterns of genetic variation.Bernard Y. Kim, Christian D. Huber, Kirk E. Lohmuelle

Beyond Blobs in Percolation Cluster Structure: The Distribution of 3-Blocks at the Percolation Threshold

The incipient infinite cluster appearing at the bond percolation threshold can be decomposed into singly-connected ``links'' and multiply-connected ``blobs.'' Here we decompose blobs into objects known in graph theory as 3-blocks. A 3-block is a graph that cannot be separated into disconnected subgraphs by cutting the graph at 2 or fewer vertices. Clusters, blobs, and 3-blocks are special cases of $k$-blocks with $k=1$, 2, and 3, respectively. We study bond percolation clusters at the percolation threshold on 2-dimensional square lattices and 3-dimensional cubic lattices and, using Monte-Carlo simulations, determine the distribution of the sizes of the 3-blocks into which the blobs are decomposed. We find that the 3-blocks have fractal dimension $d_3=1.2\pm 0.1$ in 2D and $1.15\pm 0.1$ in 3D. These fractal dimensions are significantly smaller than the fractal dimensions of the blobs, making possible more efficient calculation of percolation properties. Additionally, the closeness of the estimated values for $d_3$ in 2D and 3D is consistent with the possibility that $d_3$ is dimension independent. Generalizing the concept of the backbone, we introduce the concept of a ``$k$-bone'', which is the set of all points in a percolation system connected to $k$ disjoint terminal points (or sets of disjoint terminal points) by $k$ disjoint paths. We argue that the fractal dimension of a $k$-bone is equal to the fractal dimension of $k$-blocks, allowing us to discuss the relation between the fractal dimension of $k$-blocks and recent work on path crossing probabilities.Comment: All but first 2 figs. are low resolution and are best viewed when printe

The role of genetic selection and climatic factors in the dispersal of anatomically modern humans out of Africa.

The evolutionarily recent dispersal of anatomically modern humans (AMH) out of Africa (OoA) and across Eurasia provides a unique opportunity to examine the impacts of genetic selection as humans adapted to multiple new environments. Analysis of ancient Eurasian genomic datasets (~1,000 to 45,000 y old) reveals signatures of strong selection, including at least 57 hard sweeps after the initial AMH movement OoA, which have been obscured in modern populations by extensive admixture during the Holocene. The spatiotemporal patterns of these hard sweeps provide a means to reconstruct early AMH population dispersals OoA. We identify a previously unsuspected extended period of genetic adaptation lasting ~30,000 y, potentially in the Arabian Peninsula area, prior to a major Neandertal genetic introgression and subsequent rapid dispersal across Eurasia as far as Australia. Consistent functional targets of selection initiated during this period, which we term the Arabian Standstill, include loci involved in the regulation of fat storage, neural development, skin physiology, and cilia function. Similar adaptive signatures are also evident in introgressed archaic hominin loci and modern Arctic human groups, and we suggest that this signal represents selection for cold adaptation. Surprisingly, many of the candidate selected loci across these groups appear to directly interact and coordinately regulate biological processes, with a number associated with major modern diseases including the ciliopathies, metabolic syndrome, and neurodegenerative disorders. This expands the potential for ancestral human adaptation to directly impact modern diseases, providing a platform for evolutionary medicine.Raymond Tobler, Yassine Souilmi, Christian D. Huber, and Alan Coope

Extrusión apical y su relación con la preparación biomecánica del conducto radicular

La preparación químico-mecánica del conducto radicular (CR) durante un tratamiento endodóntico puede causar daño a los tejidos periapicales por la extrusión apical de los desechos y ser el origen del dolor postoperatorio. El presente trabajo tiene por objetivo actualizar y analizar trabajos de investigación sobre extrusión apical producidos en el Glide Path y en la preparación biomecánica del conducto radicular. Se realizó una revisión bibliográfica en bases electrónicas (SCIELO, MEDLINE, EBSCO, LILACS, PUBMED), revisando artículos en español, inglés y portugués, determinando como criterios de inclusión: estudios in vitro publicados en los últimos 10 años, que hayan obtenido medición de desechos apicales por instrumentación mecanizada y manual en el Glide Path apical y conformación del CR (instrumentación, irrigación y recuento bacteriano a partir de desechos extruidos), y como criterios de exclusión, artículos de más de 10 años de publicación, aquellos que comparan limas manuales entre sí; exclusivamente sin instrumentación mecanizada, desobturación del CR y los que no incluyan medición de extrusión apical. Se concluye que todos los procedimientos durante el tratamiento endodóntico generan extrusión apical. El Glide Path con instrumentación mecanizada reduce los desechos extruidos. Los sistemas alternativos producen mayor extrusión apical, disminuye cuando se realiza un Glide Path con limas rotatorias previamente ya que estas La preparación químico-mecánica del conducto radicular (CR) durante un tratamiento endodóntico puede causar daño a los tejidos periapicales por la extrusión apical de los desechos y ser el origen del dolor postoperatorio. El presente trabajo tiene por objetivo actualizar y analizar trabajos de investigación sobre extrusión apical producidos en el Glide Path y en la preparación biomecánica del conducto radicular. Se realizó una revisión bibliográfica en bases electrónicas (SCIELO, MEDLINE, EBSCO, LILACS, PUBMED), revisando artículos en español, inglés y portugués, determinando como criterios de inclusión: estudios in vitro publicados en los últimos 10 años, que hayan obtenido medición de desechos apicales por instrumentación mecanizada y manual en el Glide Path apical y conformación del CR (instrumentación, irrigación y recuento bacteriano a partir de desechos extruidos), y como criterios de exclusión, artículos de más de 10 años de publicación, aquellos que comparan limas manuales entre sí; exclusivamente sin instrumentación mecanizada, desobturación del CR y los que no incluyan medición de extrusión apical. Se concluye que todos los procedimientos durante el tratamiento endodóntico generan extrusión apical. El Glide Path con instrumentación mecanizada reduce los desechos extruidos. Los sistemas alternativos producen mayor extrusión apical, disminuye cuando se realiza un Glide Path con limas rotatorias previamente ya que estas impulsan estos desechos hacia coronal. La instrumentación manual genera más extrusión que la instrumentación mecanizada. La reducción en el número de instrumentos utilizados en la conformación disminuye la extrusión de desechos. La extrusión de bacterias en el Glide Path con limas K es mayor en comparación a las técnicas rotatorias y reciprocantes. La irrigación ultrasónica pasiva PUI promovió mayor cantidad de detritus y extrusión bacteriana y se recomienda el uso de agujas de pequeño diámetro (27 G o 30 G), la extrusión apical del irrigante es menor cuando ésta se realiza con agujas con ventilación lateral

Precision Electroweak Data and Unification of Couplings in Warped Extra Dimensions

Warped extra dimensions allow a novel way of solving the hierarchy problem, with all fundamental mass parameters of the theory naturally of the order of the Planck scale. The observable value of the Higgs vacuum expectation value is red-shifted, due to the localization of the Higgs field in the extra dimension. It has been recently observed that, when the gauge fields propagate in the bulk, unification of the gauge couplings may be achieved. Moreover, the propagation of fermions in the bulk allows for a simple solution to potentially dangerous proton decay problems. However, bulk gauge fields and fermions pose a phenomenological challenge, since they tend to induce large corrections to the precision electroweak observables. In this article, we study in detail the effect of gauge and fermion fields propagating in the bulk in the presence of gauge brane kinetic terms compatible with gauge coupling unification, and we present ways of obtaining a consistent description of experimental data, while allowing values of the first Kaluza Klein mode masses of the order of a few TeV.Comment: 32 pages, 7 figures. References adde

Field localization in warped gauge theories

We present four-dimensional gauge theories that describe physics on five-dimensional curved (warped) backgrounds, which includes bulk fields with various spins (vectors, spinors, and scalars). Field theory on the AdS$_5$ geometry is examined as a simple example of our formulation. Various properties of bulk fields on this background, e.g., the mass spectrum and field localization behavior, can be achieved within a fully four-dimensional framework. Moreover, that gives a localization mechanism for massless vector fields. We also consider supersymmetric cases, and show in particular that the conditions on bulk masses imposed by supersymmetry on warped backgrounds are derived from a four-dimensional supersymmetric theory on the flat background. As a phenomenological application, models are shown to generate hierarchical Yukawa couplings. Finally, we discuss possible underlying mechanisms which dynamically realize the required couplings to generate curved geometries.Comment: 24 pages, 12 figures; more explanation of nonuniversal gauge couplings added, typos corrected, references update

Competing orders in a magnetic field: spin and charge order in the cuprate superconductors

We describe two-dimensional quantum spin fluctuations in a superconducting Abrikosov flux lattice induced by a magnetic field applied to a doped Mott insulator. Complete numerical solutions of a self-consistent large N theory provide detailed information on the phase diagram and on the spatial structure of the dynamic spin spectrum. Our results apply to phases with and without long-range spin density wave order and to the magnetic quantum critical point separating these phases. We discuss the relationship of our results to a number of recent neutron scattering measurements on the cuprate superconductors in the presence of an applied field. We compute the pinning of static charge order by the vortex cores in the `spin gap' phase where the spin order remains dynamically fluctuating, and argue that these results apply to recent scanning tunnelling microscopy (STM) measurements. We show that with a single typical set of values for the coupling constants, our model describes the field dependence of the elastic neutron scattering intensities, the absence of satellite Bragg peaks associated with the vortex lattice in existing neutron scattering observations, and the spatial extent of charge order in STM observations. We mention implications of our theory for NMR experiments. We also present a theoretical discussion of more exotic states that can be built out of the spin and charge order parameters, including spin nematics and phases with `exciton fractionalization'.Comment: 36 pages, 33 figures; for a popular introduction, see http://onsager.physics.yale.edu/superflow.html; (v2) Added reference to new work of Chen and Ting; (v3) reorganized presentation for improved clarity, and added new appendix on microscopic origin; (v4) final published version with minor change