Genetic Distance between Species Predicts Novel Trait Expression in Their Hybrids

Interspecific hybridization can generate transgressive hybrid phenotypes with extreme trait values exceeding the combined range of the parental species. Such variation can enlarge the working surface for natural selection, and may facilitate the evolution of novel adaptations where ecological opportunity exists. The number of quantitative trait loci fixed for different alleles in different species should increase with time since speciation. If transgression is caused by complementary gene action or epistasis, hybrids between more distant species should be more likely to display transgressive phenotypes. To test this prediction we collected data on transgression frequency from the literature, estimated genetic distances between the hybridizing species from gene sequences, and calculated the relationship between the two using phylogenetically controlled methods. We also tested if parental phenotypic divergence affected the occurrence of transgression. We found a highly significant positive correlation between transgression frequency and genetic distance in eudicot plants explaining 43% of the variance in transgression frequency. In total, 36% of the measured traits were transgressive. The predicted effect of time since speciation on transgressive segregation was unconfounded by the potentially conflicting effects of phenotypic differentiation between species. Our analysis demonstrates that the potential impact hybridization may have on phenotypic evolution is predictable from the genetic distance between species.

Phenotypic novelty in experimental hybrids is predicted by the genetic distance between species of cichlid fish

Background: Transgressive segregation describes the occurrence of novel phenotypes in hybrids with extreme trait values not observed in either parental species. A previously experimentally untested prediction is that the amount of transgression increases with the genetic distance between hybridizing species. This follows from QTL studies suggesting that transgression is most commonly due to complementary gene action or epistasis, which become more frequent at larger genetic distances. This is because the number of QTLs fixed for alleles with opposing signs in different species should increase with time since speciation provided that speciation is not driven by disruptive selection. We measured the amount of transgression occurring in hybrids of cichlid fish bred from species pairs with gradually increasing genetic distances and varying phenotypic similarity. Transgression in multi-trait shape phenotypes was quantified using landmark-based geometric morphometric methods. Results: We found that genetic distance explained 52% and 78% of the variation in transgression frequency in F1 and F2 hybrids, respectively. Confirming theoretical predictions, transgression when measured in F2 hybrids, increased linearly with genetic distance between hybridizing species. Phenotypic similarity of species on the other hand was not related to the amount of transgression. Conclusion: The commonness and ease with which novel phenotypes are produced in cichlid hybrids between unrelated species has important implications for the interaction of hybridization with adaptation and speciation. Hybridization may generate new genotypes with adaptive potential that did not reside as standing genetic variation in either parental population, potentially enhancing a population's responsiveness to selection. Our results make it conceivable that hybridization contributed to the rapid rates of phenotypic evolution in the large and rapid adaptive radiations of haplochromine cichlids.

Phenotypic divergence but not genetic distance predicts assortative mating among species of a cichlid fish radiation

The hypothesis of ecological divergence giving rise to premating isolation in the face of gene flow is controversial. However, this may be an important mechanism to explain the rapid multiplication of species during adaptive radiation following the colonization of a new environment when geographical barriers to gene flow are largely absent but underutilized niche space is abundant. Using cichlid fish, we tested the prediction of ecological speciation that the strength of premating isolation among species is predicted by phenotypic rather than genetic distance. We conducted mate choice experiments between three closely related, sympatric species of a recent radiation in Lake Mweru (Zambia/DRC) that differ in habitat use and phenotype, and a distantly related population from Lake Bangweulu that resembles one of the species in Lake Mweru. We found significant assortative mating among all closely related, sympatric species that differed phenotypically, but none between the distantly related allopatric populations of more similar phenotype. Phenotypic distance between species was a good predictor of the strength of premating isolation, suggesting that assortative mating can evolve rapidly in association with ecological divergence during adaptive radiation. Our data also reveals that distantly related allopatric populations that have not diverged phenotypically, may hybridize when coming into secondary contact, e.g. upon river capture because of diversion of drainage systems.

Effect of immune pressure on hepatitis C virus evolution: insights from a single-source outbreak

The host's immune response to hepatitis C virus (HCV) can result in the selection of characteristic mutations (adaptations) that enable the virus to escape this response. The ability of the virus to mutate at these sites is dependent on the incoming virus, the fitness cost incurred by the mutation, and the benefit to the virus in escaping the response. Studies examining viral adaptation in chronic HCV infection have shown that these characteristic immune escape mutations can be observed at the population level as human leukocyte antigen (HLA)-specific viral polymorphisms. We examined 63 individuals with chronic HCV infection who were infected from a single HCV genotype 1b source. Our aim was to determine the extent to which the host's immune pressure affects HCV diversity and the ways in which the sequence of the incoming virus, including preexisting escape mutations, can influence subsequent mutations in recipients and infection outcomes. Conclusion: HCV sequences from these individuals revealed 29 significant associations between specific HLA types within the new hosts and variations within their viruses, which likely represent new viral adaptations. These associations did not overlap with previously reported adaptations for genotypes 1a and 3a and possibly reflected a combination of constraint due to the incoming virus and genetic distance between the strains. However, these sites accounted for only a portion of the sites in which viral diversity was observed in the new hosts. Furthermore, preexisting viral adaptations in the incoming (source) virus likely influenced the outcomes in the new hosts.

The Accumulation of Reproductive Incompatibilities in African Cichlid Fish

The rate at which different components of reproductive isolation accumulate with divergence time between species has only been studied in a limited, but growing, number of species. We measured premating isolation and hybrid inviability at four different ontogenetic stages from zygotes to adults in interspecific hybrids of 26 pairs of African cichlid species, spanning the entire East African haplochromine radiation. We then used multiple relaxed molecular clock calibrations to translate genetic distances into absolute ages to compare evolutionary rates of different components of reproductive isolation. We find that premating isolation accumulates fast initially but then changes little with increasing genetic distance between species. In contrast, postmating isolation between closely related species is negligible but then accumulates rapidly, resulting in complete hybrid inviability after 4.4/8.5/18.4 million years (my). Thus, the rate at which complete intrinsic incompatibilities arise in this system is orders of magnitude lower than rates of speciation within individual lake radiations. Together these results suggest divergent ecological adaptations may prevent populations from interbreeding and help maintain cichlid species diversity, which may be vulnerable to environmental degradation. By quantifying the capacity to produce viable hybrids between allopatric, distantly related lineages our results also provide an upper divergence time limit for the "hybrid swarm origin" model of adaptive radiation.

Treatment-naive individuals are the major source of transmitted HIV-1 drug resistance in men who have sex with men in the Swiss HIV Cohort Study

BACKGROUND Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR. METHODS ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates. RESULTS One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F. CONCLUSIONS Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.

Eco-evolutionary Dynamics of Individual-Based Food Webs

The past decade has seen the rise of high resolution datasets. One of the main surprises of analysing such data has been the discovery of a large genetic, phenotypic and behavioural variation and heterogeneous metabolic rates among individuals within natural populations. A parallel discovery from theory and experiments has shown a strong temporal convergence between evolutionary and ecological dynamics, but a general framework to analyse from individual-level processes the convergence between ecological and evolutionary dynamics and its implications for patterns of biodiversity in food webs has been particularly lacking. Here, as a first approximation to take into account intraspecific variability and the convergence between the ecological and evolutionary dynamics in large food webs, we develop a model from population genomics and microevolutionary processes that uses sexual reproduction, genetic-distance-based speciation and trophic interactions. We confront the model with the prey consumption per individual predator, species-level connectance and prey–predator diversity in several environmental situations using a large food web with approximately 25,000 sampled prey and predator individuals. We show higher than expected diversity of abundant species in heterogeneous environmental conditions and strong deviations from the observed distribution of individual prey consumption (i.e. individual connectivity per predator) in all the environmental conditions. The observed large variance in individual prey consumption regardless of the environmental variability collapsed species-level connectance after small increases in sampling effort. These results suggest (1) intraspecific variance in prey–predator interactions has a strong effect on the macroscopic properties of food webs and (2) intraspecific variance is a potential driver regulating the speed of the convergence between ecological and evolutionary dynamics in species-rich food webs. These results also suggest that genetic–ecological drift driven by sexual reproduction, equal feeding rate among predator individuals, mutations and genetic-distance-based speciation can be used as a neutral food web dynamics test to detect the ecological and microevolutionary processes underlying the observed patterns of individual and species-based food webs at local and macroecological scales.

Frequency-Dependent Selection Predicts Patterns of Radiations and Biodiversity

Most empirical studies support a decline in speciation rates through time, although evidence for constant speciation rates also exists. Declining rates have been explained by invoking pre-existing niches, whereas constant rates have been attributed to non-adaptive processes such as sexual selection and mutation. Trends in speciation rate and the processes underlying it remain unclear, representing a critical information gap in understanding patterns of global diversity. Here we show that the temporal trend in the speciation rate can also be explained by frequency-dependent selection. We construct a frequency-dependent and DNA sequence-based model of speciation. We compare our model to empirical diversity patterns observed for cichlid fish and Darwin's finches, two classic systems for which speciation rates and richness data exist. Negative frequency-dependent selection predicts well both the declining speciation rate found in cichlid fish and explains their species richness. For groups like the Darwin's finches, in which speciation rates are constant and diversity is lower, speciation rate is better explained by a model without frequency-dependent selection. Our analysis shows that differences in diversity may be driven by incipient species abundance with frequency-dependent selection. Our results demonstrate that genetic-distance-based speciation and frequency-dependent selection are sufficient to explain the high diversity observed in natural systems and, importantly, predict decay through time in speciation rate in the absence of pre-existing niches.

Hybrid Breakdown in Cichlid Fish

Studies from a wide diversity of taxa have shown a negative relationship between genetic compatibility and the divergence time of hybridizing genomes. Theory predicts the main breakdown of fitness to happen after the F1 hybrid generation, when heterosis subsides and recessive allelic (Dobzhansky-Muller) incompatibilities are increasingly unmasked. We measured the fitness of F2 hybrids of African haplochromine cichlid fish bred from species pairs spanning several thousand to several million years divergence time. F2 hybrids consistently showed the lowest viability compared to F1 hybrids and non-hybrid crosses (crosses within the grandparental species), in agreement with hybrid breakdown. Especially the short- and long-term survival (2 weeks to 6 months) of F2 hybrids was significantly reduced. Overall, F2 hybrids showed a fitness reduction of 21% compared to F1 hybrids, and a reduction of 43% compared to the grandparental, non-hybrid crosses. We further observed a decrease of F2 hybrid viability with the genetic distance between grandparental lineages, suggesting an important role for negative epistatic interactions in cichlid fish postzygotic isolation. The estimated time window for successful production of F2 hybrids resulting from our data is consistent with the estimated divergence time between the multiple ancestral lineages that presumably hybridized in three major adaptive radiations of African cichlids.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

BACKGROUND  Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS  A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS  Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS  We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.

Long distance dispersal shaped patterns of human genetic diversity in Eurasia

Most previous attempts at reconstructing the past history of human populations did not explicitly take geography into account, or considered very simple scenarios of migration and ignored environmental information. However, it is likely that the Last Glacial Maximum (LGM) affected the demography and the range of many species, including our own. Moreover, long-distance dispersal (LDD) may have been an important component of human migrations, allowing fast colonization of new territories and preserving high levels of genetic diversity. Here, we use a high-quality microsatellite dataset genotyped in 22 populations to estimate the posterior probabilities of several scenarios for the settlement of the Old World by modern humans. We considered models ranging from a simple spatial expansion to others including LDD and a LGM-induced range contraction, as well as Neolithic demographic expansions. We find that scenarios with LDD are much better supported by data than models without LDD. Nevertheless, we show evidence that LDD events to empty habitats were strongly prevented during the settlement of Eurasia. This unexpected absence of LDD ahead of the colonization wave front could have been caused by an Allee effect, either due to intrinsic causes such as an inbreeding depression built during the expansion, or to extrinsic causes such as direct competition with archaic humans. Overall, our results suggest only a relatively limited effect of the LGM-contraction on current patterns of human diversity. This is in clear contrast with the major role of LDD migrations, which have potentially contributed to the intermingled genetic structure of Eurasian populations.

Using multiple landscape genetic approaches to test the validity of genetic clusters in a species characterized by an isolation-by-distance pattern

Bayesian clustering methods are typically used to identify barriers to gene flow, but they are prone to deduce artificial subdivisions in a study population characterized by an isolation-by-distance pattern (IbD). Here we analysed the landscape genetic structure of a population of wild boars (Sus scrofa) from south-western Germany. Two clustering methods inferred the presence of the same genetic discontinuity. However, the population in question was characterized by a strong IbD pattern. While landscape-resistance modelling failed to identify landscape features that influenced wild boar movement, partial Mantel tests and multiple regression of distance matrices (MRDMs) suggested that the empirically inferred clusters were separated by a genuine barrier. When simulating random lines bisecting the study area, 60% of the unique barriers represented, according to partial Mantel tests and MRDMs, significant obstacles to gene flow. By contrast, the random-lines simulation showed that the boundaries of the inferred empirical clusters corresponded to the most important genetic discontinuity in the study area. Given the degree of habitat fragmentation separating the two empirical partitions, it is likely that the clustering programs correctly identified a barrier to gene flow. The differing results between the work published here and other studies suggest that it will be very difficult to draw general conclusions about habitat permeability in wild boar from individual studies.

Evidence of neutral and adaptive genetic divergence between European trout populations sampled along altitudinal gradients

Species with a wide geographical distribution are often composed of distinct subgroups which may be adapted to their local environment. European trout (Salmo trutta species complex) provide an example of such a complex consisting of several genetically and ecologically distinct forms. However, trout populations are strongly influenced by human activities, and it is unclear to what extent neutral and adaptive genetic differences have persisted. We sampled 30 Swiss trout populations from heterogeneous environments along replicated altitudinal gradients in three major European drainages. More than 850 individuals were genotyped at 18 microsatellite loci which included loci diagnostic for evolutionary lineages and candidate markers associated with temperature tolerance, reproductive timing and immune defence. We find that the phylogeographic structure of Swiss trout populations has not been completely erased by stocking. Distinct genetic clusters corresponding to the different drainages could be identified, although nonindigenous alleles were clearly present, especially in the two Mediterranean drainages. We also still detected neutral genetic differentiation within rivers which was often associated with the geographical distance between populations. Five loci showed evidence of divergent selection between populations with several drainage-specific patterns. Lineage-diagnostic markers, a marker linked to a quantitative trait locus for upper temperature tolerance in other salmonids and a marker linked to the major histocompatibility class I gene were implicated in local adaptation and some patterns were associated with altitude. In contrast, tentative evidence suggests a signal of balancing selection at a second immune relevant gene (TAP2). Our results confirm the persistence of both neutral and potentially adaptive genetic differences between trout populations in the face of massive human-mediated dispersal.

Fine-scale genetic structure and dispersal in the common vole (Microtus arvalis)

The genetic structure and demography of local populations is tightly linked to the rate and scale of dispersal. Dispersal parameters are notoriously difficult to determine in the field, and remain often completely unknown for smaller organisms. In this study, we investigate spatial and temporal genetic structure in relation to dispersal patterns among local populations of the probably most abundant European mammals, the common vole (Microtus arvalis). Voles were studied in six natural populations at distances of 0.4-2.5 km in three different seasons (fall, spring, summer) corresponding to different life-history stages. Field observations provided no direct evidence for movements of individuals between populations. The analysis of 10 microsatellite markers revealed a persistent overall genetic structure among populations of 2.9%, 2.5% and 3% FST in the respective season. Pairwise comparisons showed that even the closest populations were significantly differentiated from each other in each season, but there was no evidence for temporal differentiation within populations or isolation by distance among populations. Despite significant genetic structure, assignment analyses identified a relatively high proportion of individuals as being immigrants for the population where they were captured. The immigration rate was not significantly lower for females than for males. We suggest that a generally low and sex-dependent effective dispersal rate as the consequence of only few immigrants reproducing successfully in the new populations together with the social structure within populations may explain the maintenance of genetic differentiation among populations despite migration.