Effects of a change in the level of inbreeding on the genetic load

"The effects of inbreeding may not be as noticeable in the first generation as the invigoration immediately apparent after crossing". This statement, published in 1919, has received little attention, and has apparently never been tested empirically, although the reduction of the genetic load of populations by inbreeding is well known in theoretical terms. Because inbreeding increases homozygosity, and hence the effectiveness of selection against recessive or partially recessive detrimental alleles, changes in levels of inbreeding can lead to a reduction in the frequencies of such mutant alleles. This results in equilibration at higher population mean fitness and is referred to as 'purging' populations of their genetic load. Severe inbreeding can also reduce genetic load due to overdominant alleles, provided selection coefficients are not symmetrical at all loci, because alleles giving lower fitness will be reduced in frequency at equilibrium. With either fitness model, however, reduction in genetic load takes time, and the initial effect of an increase in inbreeding is reduced fitness due to homozygosity. There are few data relating to the extent to which fitness is reduced during inbreeding in a set of lines and to how long the reduction lasts before increasing again to the initial level, or higher. Inbreeding experiments involving sib mating in mice and Drosophila subobscura, and successive bottlenecks in house flies have yielded some evidence consistent with the purging hypothesis. Here, we report results of an experiment demonstrating a prolonged time-course of recovery of mean fitness under self-fertilization of a naturally outcrossing plant, and also compare our results with expectations derived by computer calculations. Our results show that the genetic load present in an outcrossing population can be explained only with a high mutation rate to partially recessive deleterious alleles, and that inbreeding purges the population of mutant alleles.     

Biological and biomedical implications of the co-evolution of pathogens and their hosts

Co-evolution between host and pathogen is, in principle, a powerful determinant of the biology and genetics of infection and disease. Yet co-evolution has proven difficult to demonstrate rigorously in practice, and co-evolutionary thinking is only just beginning to inform medical or veterinary research in any meaningful way, even though it can have a major influence on how genetic variation in biomedically important traits is interpreted. Improving our understanding of the biomedical significance of co-evolution will require changing the way in which we look for it, complementing the phenomenological approach traditionally favored by evolutionary biologists with the exploitation of the extensive data becoming available on the molecular biology and molecular genetics of host-pathogen interactions.     

Reduced adaptation of a non-recombining neo-Y chromosome

Sex chromosomes are generally believed to have descended from a pair of homologous autosomes. Suppression of recombination between the ancestral sex chromosomes led to the genetic degeneration of the Y chromosome. In response, the X chromosome may become dosage-compensated. Most proposed mechanisms for the degeneration of Y chromosomes involve the rapid fixation of deleterious mutations on the Y. Alternatively, Y-chromosome degeneration might be a response to a slower rate of adaptive evolution, caused by its lack of recombination. Here we report patterns of DNA polymorphism and divergence at four genes located on the neo-sex chromosomes of Drosophila miranda. We show that a higher rate of protein sequence evolution of the neo-X-linked copy of Cyclin B relative to the neo-Y copy is driven by positive selection, which is consistent with the adaptive hypothesis for the evolution of the Y chromosome. In contrast, the neo-Y-linked copies of even-skipped and roundabout show an elevated rate of protein evolution relative to their neo-X homologues, probably reflecting the reduced effectiveness of selection against deleterious mutations in a non-recombining genome. Our results provide evidence for the importance of sexual recombination for increasing and maintaining the level of adaptation of a population.     

Low variability in a Y-linked plant gene and its implications for Y-chromosome evolution

Sex chromosomes have evolved independently in several different groups of organisms, but they share common features, including genetic degeneration of the Y chromosome. Suppression of recombination between ancestral proto-X and proto-Y chromosomes is thought to have led to their gradual divergence, and to degeneration of the Y chromosome, but the evolutionary forces responsible are unknown. In non-recombining Y chromosomes, deleterious mutations may be carried to fixation by linked advantageous mutations ("selective sweeps"). Occurrence of deleterious mutations may drive "Muller's ratchet" (stochastic loss of chromosomes with the fewest mutations). Selective elimination of deleterious mutations, causing "background selection" may accelerate stochastic fixation of mildly detrimental mutations. All these processes lower effective population sizes, and therefore reduce variability of genes in evolving Y chromosomes. We have studied DNA diversity and divergence in a recently described X- and Y-linked gene pair (SLX-1 and SLY-1) of the plant Silene latifolia to obtain evidence about the early stages of Y degeneration. Here we show that DNA polymorphism in SLY-1 is 20-fold lower than in SLX-1, but the pattern of polymorphism does not suggest a selective sweep.     

Covert skill learning in a cortical-basal ganglia circuit

We learn complex skills such as speech and dance through a gradual process of trial and error. Cortical-basal ganglia circuits have an important yet unresolved function in this trial-and-error skill learning; influential 'actor-critic' models propose that basal ganglia circuits generate a variety of behaviours during training and learn to implement the successful behaviours in their repertoire. Here we show that the anterior forebrain pathway (AFP), a cortical-basal ganglia circuit, contributes to skill learning even when it does not contribute to such 'exploratory' variation in behavioural performance during training. Blocking the output of the AFP while training Bengalese finches to modify their songs prevented the gradual improvement that normally occurs in this complex skill during training. However, unblocking the output of the AFP after training caused an immediate transition from naive performance to excellent performance, indicating that the AFP covertly gained the ability to implement learned skill performance without contributing to skill practice. In contrast, inactivating the output nucleus of the AFP during training completely prevented learning, indicating that learning requires activity within the AFP during training. Our results suggest a revised model of skill learning: basal ganglia circuits can monitor the consequences of behavioural variation produced by other brain regions and then direct those brain regions to implement more successful behaviours. The ability of the AFP to identify successful performances generated by other brain regions indicates that basal ganglia circuits receive a detailed efference copy of premotor activity in those regions. The capacity of the AFP to implement successful performances that were initially produced by other brain regions indicates precise functional connections between basal ganglia circuits and the motor regions that directly control performance.