Effect of beneficial sweeps and background selection on genetic diversity in changing environments.

Neutral theory predicts that the genetic diversity within a population is proportional to the effective population size. In contrast, the observed genetic diversity for various species vary in a narrow range for several orders of magnitude change in the population sizes (Lewontin's paradox). The selective sweeps and background selection, reduce the genetic variation at the linked neutral sites and have been studied considering the environment to be selectively constant. However, in a natural population, the selective environment varies with time. Here, we investigate the impact of selective sweeps and background selection on neutral genetic diversity when the selection coefficient changes periodically over time. The reduction in genetic variation due to selective sweeps is known to depend on the conditional fixation time. Here, we find that the effect of changing environment on conditional mean fixation time is most substantial for the randomly mating population than the inbreeding population with arbitrary inbreeding coefficient. We also study the effect of background selection on neutral sites when the selection coefficient of linked deleterious mutation change periodically in time. In the slowly changing environment, we find that neutral heterozygosity is significantly different, and the site frequency spectrum has a different shape than that in the static environment.

Joint effect of changing selection and demography on the site frequency spectrum.

The site frequency spectrum (SFS) is an important statistic that summarizes the molecular variation in a population, and is used to estimate population-genetic parameters and detect natural selection. Here, we study the SFS in a randomly mating, diploid population in which both the population size and selection coefficient vary periodically with time using a diffusion theory approach, and derive simple analytical expressions for the time-averaged SFS in slowly and rapidly changing environments. We show that for strong selection and in slowly changing environments where the population experiences both positive and negative cycles of the selection coefficient, the time-averaged SFS differs significantly from the equilibrium SFS in a constant environment. The deviation is found to depend on the time spent by the population in the deleterious part of the selection cycle and the phase difference between the selection coefficient and population size, and can be captured by an effective population size.

Time to fixation in changing environments.

Although many experimental and theoretical studies on natural selection have been carried out in a constant environment, as natural environments typically vary in time, it is important to ask if and how the results of these investigations are affected by a changing environment. Here, we study the properties of the conditional fixation time defined as the time to fixation of a new mutant that is destined to fix in a finite, randomly mating diploid population with intermediate dominance that is evolving in a periodically changing environment. It is known that in a static environment, the conditional mean fixation time of a co-dominant beneficial mutant is equal to that of a deleterious mutant with the same magnitude of selection coefficient. We find that this symmetry is not preserved, even when the environment is changing slowly. More generally, we find that the conditional mean fixation time of an initially beneficial mutant in a slowly changing environment depends weakly on the dominance coefficient and remains close to the corresponding result in the static environment. However, for an initially deleterious mutant under moderate and slowly varying selection, the fixation time differs substantially from that in a constant environment when the mutant is recessive. As fixation times are intimately related to the levels and patterns of genetic diversity, our results suggest that for beneficial sweeps, these quantities are only mildly affected by temporal variation in environment. In contrast, environmental change is likely to impact the patterns due to recessive deleterious sweeps strongly.

Catatonia Update.

Catatonia is a neuropsychiatric condition characterized by physical presentations ranging from profound immobility to excessive motor activity. Emotional aspects of catatonia vary clinically between psychomotor retardation and extreme excitability. In the past, catatonia was considered to be a variant of schizophrenia. However, the disorder actually occurs as a clinical expression of many different psychiatric, neurologic, or medical diagnoses. A prompt diagnostic evaluation should identify any underlying diseases with consideration of somatic pathologies, especially those affecting central nervous system function. The workup focuses on a range of metabolic, traumatic, infectious, degenerative, autoimmune, drug-related, or other possible conditions, including psychiatric etiologies. Appropriate interventions should be instituted as quickly as possible to avoid complications like dehydration or deep vein thromboses. Symptomatic treatment commonly includes various pharmaceuticals or electroconvulsive therapy. Benzodiazepine drugs are, and have long been, the most preferred pharmacotherapy. These medications are usually fast acting and effective, are safe, and remain the catatonia treatment of choice.