Emmanuel Milot

Evidence for evolution in response to natural selection in a contemporary human population

It is often claimed that modern humans have stopped evolving because cultural and technological advancements have annihilated natural selection. In contrast, recent studies show that selection can be strong in contemporary populations. However, detecting a response to selection is particularly challenging; previous evidence from wild animals has been criticized for both applying anticonservative statistical tests and failing to consider random genetic drift. Here we study life-history variation in an insular preindustrial French-Canadian population and apply a recently proposed conservative approach to testing microevolutionary responses to selection. As reported for other such societies, natural selection favored an earlier age at first reproduction (AFR) among women. AFR was also highly heritable and genetically correlated to fitness, predicting a microevolutionary change toward earlier reproduction. In agreement with this prediction, AFR declined from about 26–22 y over a 140-y period. Crucially, we uncovered a substantial change in the breeding values for this trait, indicating that the change in AFR largely occurred at the genetic level. Moreover, the genetic trend was higher than expected under the effect of random genetic drift alone. Our results show that microevolution can be detectable over relatively few generations in humans and underscore the need for studies of human demography and reproductive ecology to consider the role of evolutionary processes.

The seabird paradox: dispersal, genetic structure and population dynamics in a highly mobile, but philopatric albatross species

The philopatric behaviour of albatrosses has intrigued biologists due to the high mobility of these seabirds. It is unknown how albatrosses maintain a system of fragmented populations without frequent dispersal movements, in spite of the long‐term temporal heterogeneity in resource distribution at sea. We used both genetic (amplified fragment length polymorphism) and capture–mark–recapture (CMR) data to identify explicitly which among several models of population dynamics best applies to the wandering albatross (Diomedea exulans) and to test for migration–drift equilibrium. We previously documented an extremely low genetic diversity in this species. Here, we show that populations exhibit little genetic differentiation across the species’ range (ΘB < 0.05, where ΘB is an FST analogue). Furthermore, there was no evidence of hierarchical structure or isolation‐by‐distance. Wrights FST between pairs of colonies were low in general and the pattern was consistent with a nonequilibrium genetic model. In contrast, CMR data collected over the last decades indicated that about one bird per cohort has dispersed among islands. Overall, FST values were not indicative of contemporary dispersal as inferred from CMR data. Moreover, all genotypes grouped together in a cluster analysis, indicating that current colonies may have derived from one ancestral source that had a low genetic diversity. A metapopulation dynamics model including a recent (postglacial) colonization of several islands seems consistent with both the very low levels of genetic diversity and structure within the wandering albatross. Yet, our data suggest that several other factors including ongoing gene flow, recurrent long‐distance dispersal and source‐sink dynamics have contributed to different extent in shaping the genetic signature observed in this species. Our results show that an absence of genetic structuring may in itself reveal little about the true population dynamics in seabirds, but can provide insights into important processes when a comparison with other information, such as demographic data, is possible.

Inflamm‐aging does not simply reflect increases in pro‐inflammatory markers

Many biodemographic studies use biomarkers of inflammation to understand or predict chronic disease and aging. Inflamm-aging, i.e. chronic low-grade inflammation during aging, is commonly characterized by pro-inflammatory biomarkers. However, most studies use just one marker at a time, sometimes leading to conflicting results due to complex interactions among the markers. A multidimensional approach allows a more robust interpretation of the various relationships between the markers. We applied principal component analysis (PCA) to 19 inflammatory biomarkers from the InCHIANTI study. We identified a clear, stable structure among the markers, with the first axis explaining inflammatory activation (both pro- and anti-inflammatory markers loaded strongly and positively) and the second axis innate immune response. The first but not the second axis was strongly correlated with age (r=0.56, p<0.0001, r=0.08 p=0.053), and both were strongly predictive of mortality (hazard ratios per PCA unit (95% CI): 1.33 (1.16-1.53) and 0.87 (0.76-0.98) respectively) and multiple chronic diseases, but in opposite directions. Both axes were more predictive than any individual markers for baseline chronic diseases and mortality. These results show that PCA can uncover a novel biological structure in the relationships among inflammatory markers, and that key axes of this structure play important roles in chronic disease.

Surviving with low genetic diversity: the case of albatrosses.

Low genetic diversity is predicted to negatively impact species viability and has been a central concern for conservation. In contrast, the possibility that some species may thrive in spite of a relatively poor diversity has received little attention. The wandering and Amsterdam albatrosses (Diomedea exulans and Diomedea amsterdamensis) are long-lived seabirds standing at an extreme along the gradient of life strategies, having traits that may favour inbreeding and low genetic diversity. Divergence time of the two species is estimated at 0.84 Myr ago from cytochrome b data. We tested the hypothesis that both albatrosses inherited poor genetic diversity from their common ancestor. Within the wandering albatross, per cent polymorphic loci and expected heterozygosity at amplified fragment length polymorphisms were approximately one-third of the minimal values reported in other vertebrates. Genetic diversity in the Amsterdam albatross, which is recovering from a severe bottleneck, was about twice as low as in the wandering albatross. Simulations supported the hypothesis that genetic diversity in albatrosses was already depleted prior to their divergence. Given the generally high breeding success of these species, it is likely that they are not suffering much from their impoverished diversity. Whether albatrosses are unique in this regard is unknown, but they appear to challenge the classical view about the negative consequences of genetic depletion on species survival.

Reduced fitness of Atlantic salmon released in the wild after one generation of captive breeding

Salmonids rank among the most socioeconomically valuable fishes and the most targeted species by stocking with hatchery‐reared individuals. Here, we used molecular parentage analysis to assess the reproductive success of wild‐ and hatchery‐born Atlantic salmon over three consecutive years in a small river in Québec. Yearly restocking in this river follows a single generation of captive breeding. Among the adults returning to the river to spawn, between 11% and 41% each year were born in hatchery. Their relative reproductive success (RRS) was nearly half that of wild‐born fish (0.55). RRS varied with life stage, being 0.71 for fish released at the fry stage and 0.42 for fish released as smolt. The lower reproductive success of salmon released as smolt was partly mediated by the modification of the proportion of single‐sea‐winter/multi‐sea‐winter fish. Overall, our results suggest that modifications in survival and growth rates alter the life‐history strategies of these fish at the cost of their reproductive success. Our results underline the potential fitness decrease, warn on long‐term evolutionary consequences for the population of repeated stocking and support the adoption of more natural rearing conditions for captive juveniles and their release at a younger stage, such as unfed fry.

Detection of a Novel, Integrative Aging Process Suggests Complex Physiological Integration

Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels of many biomarkers simultaneously by applying principal components analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans from three longitudinal cohort studies on two continents (Women’s Health and Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The first axis was associated with anemia, inflammation, and low levels of calcium and albumin. The axis structure was precisely reproduced in all three populations and in all demographic sub-populations (by sex, race, etc.); we call the process represented by the axis “integrated albunemia.” Integrated albunemia increases and accelerates with age in all populations, and predicts mortality and frailty – but not chronic disease – even after controlling for age. This suggests a role in the aging process, though causality is not yet clear. Integrated albunemia behaves more stably across populations than its component biomarkers, and thus appears to represent a higher-order physiological process emerging from the structure of underlying regulatory networks. If this is correct, detection of this process has substantial implications for physiological organization more generally.

Tug of war between continental gene flow and rearing site philopatry in a migratory bird: the sex‐biased dispersal paradigm reconsidered

Nonrandom dispersal has been recently advanced as a mechanism promoting fine‐scale genetic differentiation in resident populations, yet how this applies to species with high rates of dispersal is still unclear. Using a migratory species considered a classical example of male‐biased dispersal (the greater snow goose, Chen caerulescens atlantica), we documented a temporally stable fine‐scale genetic clustering between spatially distinct rearing sites (5–30 km apart), where family aggregates shortly after hatching. Such genetic differentiation can only arise if, in both sexes, dispersal is restricted and nonrandom, a surprising result considering that pairing occurs among mixed flocks of birds more than 3000 km away from the breeding grounds. Fine‐scale genetic structure may thus occur even in migratory species with high gene flow. We further show that looking for genetic structure based on nesting sites only may be misleading. Genetically distinct individuals that segregated into different rearing sites were in fact spatially mixed during nesting. These findings provide new, scale‐dependent links between genetic structure, pairing, and dispersal and show the importance of sampling different stages of the breeding cycle in order to detect a spatial genetic structure.

Small-scale dispersal and survival in a long-lived seabird, the wandering albatross

1. Dispersal is a fundamental but still poorly known process in population dynamics and several hypotheses have been proposed to explain its patterns. We studied natal and breeding dispersal and survival in a long-lived seabird, the wandering albatross (Diomedea exulans L.), and examined several hypotheses concerning dispersal patterns in birds. 2. We applied multi-state capture-recapture models to a 36-year data set (1969-2004) collected at three albatross colonies on Ile de Possession, Crozet Islands. Because the species has biennial reproduction, we introduced unobservable states in the model to account for the absence of individuals in those years. 3. Adults were highly faithful to their nesting colony but colony fidelity, as well as survival rate, differed slightly among colonies (fidelity ranged from 0.957 to 0.977). Breeding fidelity was highest in the colony where survival was lowest and individuals were not more likely to change colony following a failed breeding attempt than after a successful one. The colony that attracted most dispersers had the lowest density of nesting birds. 4. Philopatry (the probability that young return to breed at a birth site) was generally high but variable among colonies (ranging from 0.70 to 0.92), and survival of young differed little. Philopatry was highest in the largest colony, where the availability of potential mates was presumably greatest. However, among dispersing individuals, the colony that had the lowest density of nesting individuals, not the largest colony, attracted the most recruits. 5. Although size of the colony influenced the decision to stay or to leave in young, density was most influential in the selection of a new colony among both adult and young dispersers. Our results support the hypothesis that philopatry is the strategy favoured by most recruits and that conspecific attraction can explain variation in the level of philopatry among colonies but not settlement patterns among dispersing individuals.

Homeostatic dysregulation proceeds in parallel in multiple physiological systems

An increasing number of aging researchers believes that multi‐system physiological dysregulation may be a key biological mechanism of aging, but evidence of this has been sparse. Here, we used biomarker data on nearly 33 000 individuals from four large datasets to test for the presence of multi‐system dysregulation. We grouped 37 biomarkers into six a priori groupings representing physiological systems (lipids, immune, oxygen transport, liver function, vitamins, and electrolytes), then calculated dysregulation scores for each system in each individual using statistical distance. Correlations among dysregulation levels across systems were generally weak but significant. Comparison of these results to dysregulation in arbitrary ‘systems’ generated by random grouping of biomarkers showed that a priori knowledge effectively distinguished the true systems in which dysregulation proceeds most independently. In other words, correlations among dysregulation levels were higher using arbitrary systems, indicating that only a priori systems identified distinct dysregulation processes. Additionally, dysregulation of most systems increased with age and significantly predicted multiple health outcomes including mortality, frailty, diabetes, heart disease, and number of chronic diseases. The six systems differed in how well their dysregulation scores predicted health outcomes and age. These findings present the first unequivocal demonstration of integrated multi‐system physiological dysregulation during aging, demonstrating that physiological dysregulation proceeds neither as a single global process nor as a completely independent process in different systems, but rather as a set of system‐specific processes likely linked through weak feedback effects. These processes – probably many more than the six measured here – are implicated in aging.

Statistical Distance as a Measure of Physiological Dysregulation Is Largely Robust to Variation in Its Biomarker Composition

Physiological dysregulation may underlie aging and many chronic diseases, but is challenging to quantify because of the complexity of the underlying systems. Recently, we described a measure of physiological dysregulation, DM, that uses statistical distance to assess the degree to which an individual’s biomarker profile is normal versus aberrant. However, the sensitivity of DM to details of the calculation method has not yet been systematically assessed. In particular, the number and choice of biomarkers and the definition of the reference population (RP, the population used to define a “normal” profile) may be important. Here, we address this question by validating the method on 44 common clinical biomarkers from three longitudinal cohort studies and one cross-sectional survey. DMs calculated on different biomarker subsets show that while the signal of physiological dysregulation increases with the number of biomarkers included, the value of additional markers diminishes as more are added and inclusion of 10-15 is generally sufficient. As long as enough markers are included, individual markers have little effect on the final metric, and even DMs calculated from mutually exclusive groups of markers correlate with each other at r~0.4-0.5. We also used data subsets to generate thousands of combinations of study populations and RPs to address sensitivity to differences in age range, sex, race, data set, sample size, and their interactions. Results were largely consistent (but not identical) regardless of the choice of RP; however, the signal was generally clearer with a younger and healthier RP, and RPs too different from the study population performed poorly. Accordingly, biomarker and RP choice are not particularly important in most cases, but caution should be used across very different populations or for fine-scale analyses. Biologically, the lack of sensitivity to marker choice and better performance of younger, healthier RPs confirm an interpretation of DM physiological dysregulation and as an emergent property of a complex system.