The timing of human adaptation from Neanderthal introgression

Admixture has the potential to facilitate adaptation by providing alleles that are immediately adaptive in a new environment or by simply increasing the long-term reservoir of genetic diversity for future adaptation. A growing number of cases of adaptive introgression are being identified in species across the tree of life, however the timing of selection, and therefore the importance of the different evolutionary roles of admixture, is typically unknown. Here, we investigate the spatio-temporal history of selection favoring Neanderthal-introgressed alleles in modern human populations. Using both ancient and present-day samples of modern humans, we integrate the known demographic history of populations, namely population divergence and migration, with tests for selection. We model how a sweep placed along different branches of an admixture graph acts to modify the variance and covariance in neutral allele frequencies among populations at linked loci. Using a method based on this model of allele frequencies, we study previously identified cases of adaptive Neanderthal introgression. From these, we identify cases in which Neanderthal-introgressed alleles were quickly beneficial and other cases in which they persisted at low frequency for some time. For some of the alleles that persisted at low frequency, we show that selection likely independently favored them later on in geographically separated populations. Our work highlights how admixture with ancient hominins has contributed to modern human adaptation and contextualizes observed levels of Neanderthal ancestry in present-day and ancient samples.     

Deleterious Passengers in Adapting Populations

Most new mutations are deleterious and are eventually eliminated by natural selection. But in an adapting population, the rapid amplification of beneficial mutations can hinder the removal of deleterious variants in nearby regions of the genome, altering the patterns of sequence evolution. Here, we analyze the interactions between beneficial “driver” mutations and linked deleterious “passengers” during the course of adaptation. We derive analytical expressions for the substitution rate of a deleterious mutation as a function of its fitness cost, as well as the reduction in the beneficial substitution rate due to the genetic load of the passengers. We find that the fate of each deleterious mutation varies dramatically with the rate and spectrum of beneficial mutations and the deleterious substitution rate depends nonmonotonically on the population size and the rate of adaptation. By quantifying this dependence, our results allow us to estimate which deleterious mutations will be likely to fix and how many of these mutations must arise before the progress of adaptation is significantly reduced.     

Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy

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The mean and variance of the number of segregating sites since the last hitchhiking event

 Tight linkage may cause a reduction of nucleotide diversity in a chromosomal region if an advantageous mutation appears in that region which is driven to fixation by directional selection. This process is usually called genetic hitchhiking. If selection is strong, the entire process takes place during a time period of length 2s ln (2N) that is very short relative to 2N generations [s is the selection coefficient of the advantageous mutation and N the effective diploid population size]. On the time scale of 2N generations, which is characteristic for neutral evolution, we may therefore call this process a hitchhiking event. Using coalescent methods, we analyzed a model in which a hitchhiking event occurred in a chromosomal region of zero-recombination in the past at time x. Such a hitchhiking “catastrophe” wipes out completely genetic variation that existed in a population before that time. Standing variation observed at present must therefore be due to mutations that have arisen since time point x. Assuming that all newly arising mutations are neutral, we derived expressions for the expectation, variance and also for the higher moments of the number of nucleotide sites segregating in a sample of n genes as a function of x. The result for the first moment is then used to estimate the time back to the last hitchhiking event based on DNA polymorphism data from Drosophila. Assuming that directional selection is the sole determinant of the level of genetic variation in the gene regions surveyed, we obtained estimates of x that were typically in the order of 0.1N generations. Received 14 May 1996; received in revised form 26 August 1996     

Detecting the footprints of divergent selection in oaks with linked markers

Genome scans are increasingly used to study ecological speciation, providing a useful genome-wide perspective on divergent selection in the presence of gene flow. Here, we compare current approaches to detect footprints of divergent selection in closely related species. We analyzed 192 individuals from two interfertile European temperate oak species using 30 nuclear microsatellites from eight linkage groups. These markers present little intraspecific differentiation and can be used in combination to assign individual genotypes to species. We first show that different outlier detection tests give somewhat different results, possibly due to model constraints. Second, using linkage information for these markers, we further characterize the signature of divergent selection in the presence of gene flow. In particular, we show that recombination estimates for regions with outlier markers are lower than those for a control region, in line with a prediction from ecological speciation theory. Most importantly, we show that analyses at the haplotype level can distinguish between truly divergent (bi-directional) selection and positive selection in one of the two species, offering a new and improved method for characterizing the speciation process.     

Long-term experimental evolution in Escherichia coli. V. Effects of recombination with immigrant genotypes on the rate of bacterial evolution

This study builds upon an earlier experiment that examined the dynamics of mean fitness in evolving populations of Escherichia coli in which mutations were the sole source of genetic variation. During thousands of generations in a constant environment, the rate of improvement in mean fitness of these asexual populations slowed considerably from an initially rapid pace. In this study, we sought to determine whether sexual recombination with novel genotypes would reaccelerate the rate of adaption in these populations. To that end, treatment populations were propagated for an additional 1000 generations in the same environment as their ancestors, but they were periodically allowed to mate with an immigrant pool of genetically distinct Hfr (high frequency recombination) donors. These donors could transfer genes to the resident populations by conjugation, but the donors themselves could not grow in the experimental environment. Control populations were propagated under identical conditions, but in the absence of sexual recombination with the donors. All twelve control populations retained the ancestral alleles at every locus that was scored. In contrast, the sexual recombination treatment yielded dramatic increases in genetic variation. Thus, there was a profound effect of recombination on the rate of genetic change. However, the increased genetic variation in the treatment populations had no significant effect on the rate of adaptive evolution, as measured by changes in mean fitness relative to a common competitor. We then considered three hypotheses that might reconcile these two outcomes: recombination pressure, hitchhiking of recombinant genotypes in association with beneficial mutations, and complex selection dynamics whereby certain genotypes may have a selective advantage only within a particular milieu of competitors. The estimated recombination rate was too low to explain the observed rate of genetic change, either alone or in combination with hitchhiking effects. However, we documented comple x ecological interactions among some recombinant genotypes, suggesting that our method for estimating fitness relative to a common competitor might have underestimated the rate of adaptive evolution in the treatment populations.