Multiscale phylogeography: glacial history and autopolyploidy of Biscutella laevigata L. (Brassicaceae) in the Western Alps

Résumé Les changements climatiques du Quaternaire ont eu une influence majeure sur la distribution et l'évolution des biota septentrionaux. Les Alpes offrent un cadre spatio-temporel bien étudié pour comprendre la réactivité de la flore et le potentiel d'adaptation d'une espèce végétale face aux changements climatiques. Certaines hypothèses postulent une diversification des espèces en raison de la disparition complète de la flore des Alpes et d'un isolement important des espèces dans des refuges méridionaux durant les dernières glaciations (Tabula Rasa). Une autre hypothèse stipule le maintien de poches de résistance pour la végétation au coeur des Alpes (Nunataks). Comme de nombreuses espèces végétales présentant un grand succès écologique semblent avoir réagi aux glaciations par la multiplication de leur génome (autopolyploïdie), leur étude en milieu naturel devrait permettre de comprendre les avantages inhérents à la polyploïdie. Biscutella laevigata est un modèle emblématique de biogéographie historique, diverses études ayant montré que des populations diploïdes sont actuellement isolées dans les zones restées déglacées durant le dernier maximum glaciaire, alors que des tétraploïdes ont recolonisé l'ensemble des zones alpines mises à nu par le retrait des glaciers. Si le contexte périglaciaire semble avoir favorisé ce jeune complexe autopolyploïde, les circonstances et les avantages de cette mutation génomique ne sont pas encore clairs. Y a-t-il eu de multiples événements de polyploïdisation ? Dans quelle mesure affecte(nt)il(s) la diversité génétique et le potentiel évolutif des polyploïdes ? Les polyploïdes ont-ils une grande flexibilité génomique, favorisant une radiation adaptative, ou doivent-ils leur succès à une grande plasticité écologique ? Cette étude aborde ces questions à différentes échelles spatiales et temporelles. L'échelle régionale des Alpes occidentales permet d'aborder les facteurs distaux (aspects historiques), alors que l'échelle locale cherche à appréhender les facteurs proximaux (mécanismes évolutifs). Dans les Alpes occidentales, des populations ont été densément échantillonnées et étudiées grâce à (1) leur cytotype, (2) leur appartenance taxonomique, (3) leur habitat et (4) des marqueurs moléculaires de l'ADN chloroplastique, en vue d'établir leurs affinités évolutives. Á l'échelle locale, deux systèmes de population ont été étudiés : l'un où les populations persistent en périphérie de l'aire de distribution et l'autre au niveau du front actif de colonisation, en marge altitudinale. Les résultats à l'échelle des Alpes occidentales révèlent les sites d'intérêt (refuges glaciaires, principales barrières et voies de recolonisation) pour une espèce représentative des pelouses alpines, ainsi que pour la biodiversité régionale. Les Préalpes ont joué un rôle important dans le maintien de populations à proximité immédiate des Alpes centrales et dans l'évolution du taxon, voire de la végétation. Il est aussi démontré que l'époque glaciaire a favorisé l'autopolyploïdie polytopique et la recolonisation des Alpes occidentales par des lignées distinctes qui s'hybrident au centre des Alpes, influençant fortement leur diversité génétique et leur potentiel évolutif. L'analyse de populations locales en situations contrastées à l'aide de marqueurs AFLP montre qu'au sein d'une lignée présentant une grande expansion, la diversité génétique est façonnée par des forces évolutives différentes selon le contexte écologique et historique. Les populations persistant présentent une dispersion des gènes restreinte, engendrant une diversité génétique assez faible, mais semblent adaptées aux conditions locales de l'environnement. À l'inverse, les populations colonisant la marge altitudinale sont influencées par les effets de fondation conjugués à une importante dispersion des gènes et, si ces processus impliquent une grande diversité génétique, ils engendrent une répartition aléatoire des génotypes dans l'environnement. Les autopolyploïdes apparaissent ainsi comme capables de persister face aux changements climatiques grâce à certaines facultés d'adaptation locale et de grandes capacités à maintenir une importante diversité génétique lors de la recolonisation post-glaciaire. Summary The extreme climate changes of the Quaternary have had a major influence on species distribution and evolution. The European Alps offer a great framework to investigate flora reactivity and the adaptive potential of species under changing climate. Some hypotheses postulate diversification due to vegetation removal and important isolation in southern refugia (Tabula Rasa), while others explain phylogeographic patterns by the survival of species in favourable Nunataks within the Alps. Since numerous species have successfully reacted to past climate changes by genome multiplication (autopolyploidy), studies of such taxa in natural conditions is likely to explain the ecological success and the advantages of autopolyploidy. Early cytogeographical surveys of Biscutella laevigata have shed light on the links between autopolyploidy and glaciations by indicating that diploids are now spatially isolated in never-glaciated areas, while autotetraploids have recolonised the zones covered by glaciers- during the last glacial maximum. A periglacial context apparently favoured this young autopolyploid complex but the circumstances and the advantages of this genomic mutation remain unclear. What is the glacial history of the B. laevigata autopolyploid complex? Are there multiple events of polyploidisation? To what extent do they affect the genetic diversity and the evolutionary potential of polyploids? Is recolonisation associated with adaptive processes? How does long-term persistence affect genetic diversity? The present study addresses these questions at different spatiotemporal scales. A regional survey at the Western Alps-scale tackles distal factors (evolutionary history), while local-scale studies explore proximal factors (evolutionary mechanisms). In the Western Alps, populations have been densely sampled and studied from the (1) cytotypic, (2) morphotaxonomic, (3) habitat point of views, as well as (4) plastid DNA molecular markers, in order to infer their relationships and establish the maternal lineages phylogeography. At the local scale, populations persisting at the rear edge and populations recolonising the attitudinal margin at the leading edge have been studied by AFLPs to show how genetic diversity is shaped by different evolutionary forces across the species range. The results at the regional scale document the glacial history of a widespread species, representative of alpine meadows, in a regional area of main interest (glacial refugia, main barriers and recolonisation routes) and points out to sites of interest for regional biodiversity. The external Alps have played a major role in the maintenance of populations near the central Alps during the Last Glacial Maximum and influenced the evolution of the species, and of vegetation. Polytopic autopolyploidy in different biogeographic districts is also demonstrated. The species has had an important and rapid radiation because recolonisation took place from different refugia. The subsequent recolonisation of the Western Alps was achieved by independent lineages that are presently admixing in the central Alps. The role of the Pennic summit line is underlined as a great barrier that was permeable only through certain favourable high-altitude passes. The central Alps are thus viewed as an important crossroad where genomes with different evolutionary histories are meeting and admixing. The AFLP analysis and comparison of local populations growing in contrasted ecological and historical situations indicate that populations persisting in the external Alps present restricted gene dispersal and low genetic diversity but seem in equilibrium with their environment. On the contrary, populations colonising the attitudinal margin are mainly influenced by founder effects together with great gene dispersal and genotypes have a nearly random distribution, suggesting that recolonisation is not associated with adaptive processes. Autopolyploids that locally persist against climate changes thus seem to present adaptive ability, while those that actively recolonise the Alps are successful because of their great capacity to maintain a high genetic diversity against founder effects during recolonisation.

History of diabetes and risk of head and neck cancer: a pooled analysis from the international head and neck cancer epidemiology consortium.

BACKGROUND: A history of diabetes is associated with an increased risk of several types of cancers. Whether diabetes is a risk factor for head and neck cancer (HNC) has received little attention. METHODS: We pooled data from 12 case-control studies including 6,448 cases and 13,747 controls, and estimated odds ratios (OR) and 95% confidence intervals (CI) for the associations between diabetes and HNC, adjusted for age, education level, sex, race/ethnicity, study center, cigarette smoking, alcohol use and body mass index (BMI). RESULTS: We observed a weak association between diabetes and the incidence of HNC overall (OR, 1.09; 95% CI, 0.95-1.24). However, we observed a modest association among never smokers (OR, 1.59; 95% CI, 1.22-2.07), and no association among ever smokers (OR, 0.96; 95% CI, 0.83-1.11); likelihood ratio test for interaction p=0.001. CONCLUSIONS: A history of diabetes was weakly associated with HNC overall, but we observed evidence of effect modification by smoking status, with a positive association among those who never smoked cigarettes. Impact: This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNC risk, possibly providing new strategies in the prevention of HNC.

Genetic and environmental effects on the covariation betweencolour polymorphism and a life history trait

Variation in coloration with a strong underlying genetic basis is frequently found within animal populations but little is known about its function. Covariation between colour polymorphism and life-history traits can arise because morphs perform differently among environments or because they possess alternative alleles coding for key life-history traits. To test these two hypotheses, we studied a population of tawny owls Strix aluco, a bird displaying red, brown and grey morphs. We assessed the colour morph of breeding females, swapped eggs or hatchlings between pairs of nests, and examined how body condition in 3-week-old nestlings covaries with coloration of foster and genetic mothers. Redder foster and genetic mothers produced young in better condition. Because in two other years we observed that greyish females produced offspring in better condition than those of red females, the present study suggests that colour polymorphism signals genetic and phenotypic adaptations to cope with a fluctuating environment.

Mitochondrial uncoupling as a regulator of life-history trajectories in birds: an experimental study in the zebra finch.

Mitochondria have a fundamental role in the transduction of energy from food into ATP. The coupling between food oxidation and ATP production is never perfect, but may nevertheless be of evolutionary significance. The 'uncoupling to survive' hypothesis suggests that 'mild' mitochondrial uncoupling evolved as a protective mechanism against the excessive production of damaging reactive oxygen species (ROS). Because resource allocation and ROS production are thought to shape animal life histories, alternative life-history trajectories might be driven by individual variation in the degree of mitochondrial uncoupling. We tested this hypothesis in a small bird species, the zebra finch (Taeniopygia guttata), by treating adults with the artificial mitochondrial uncoupler 2,4-dinitrophenol (DNP) over a 32-month period. In agreement with our expectations, the uncoupling treatment increased metabolic rate. However, we found no evidence that treated birds enjoyed lower oxidative stress levels or greater survival rates, in contrast to previous results in other taxa. In vitro experiments revealed lower sensitivity of ROS production to DNP in mitochondria isolated from skeletal muscles of zebra finch than mouse. In addition, we found significant reductions in the number of eggs laid and in the inflammatory immune response in treated birds. Altogether, our data suggest that the 'uncoupling to survive' hypothesis may not be applicable for zebra finches, presumably because of lower effects of mitochondrial uncoupling on mitochondrial ROS production in birds than in mammals. Nevertheless, mitochondrial uncoupling appeared to be a potential life-history regulator of traits such as fecundity and immunity at adulthood, even with food supplied ad libitum.

Mortality associated with diabetes mellitus in comparison with history of cardiovascular disease in older women.

BACKGROUND: Women with diabetes mellitus have an increased risk of cardiovascular disease (CVD) mortality and current treatment guidelines consider diabetes to be equivalent to existing CVD, but few data exist about the relative importance of these risk factors for total and cause-specific mortality in older women. METHODS: We studied 9704 women aged ≥65 years enrolled in a prospective cohort study (Study of Osteoporotic Fractures) during a mean follow-up of 13 years and compared all-cause, CVD and coronary heart disease (CHD) mortality among non-diabetic women without and with a prior history of CVD at baseline and diabetic women without and with a prior history of CVD. Diabetes mellitus and prior CVD (history of angina, myocardial infarction or stroke) were defined as self-report of physician diagnoses. Cause of death was adjudicated from death certificates and medical records when available (>95% deaths confirmed). Ascertainment of vital status was 99% complete. Log-rank tests for the rates of death and multivariate Cox hazard models adjusted for age, smoking, physical activity, systolic blood pressure, waist girth and education were used to compare mortality among the four groups with non-diabetic women without CVD as the referent group. Results are reported as adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: At baseline mean age was 71.7±5.3 years, 7.0% reported diabetes mellitus and 14.5% reported prior CVD. 4257 women died during follow-up, 36.6% were attributed to CVD. The incidence of CVD death per 1000 person-years was 9.9 and 21.6 among non-diabetic women without and with CVD, respectively, and 23.8 and 33.3 among diabetic women without and with CVD, respectively. Compared to nondiabetic women without prior CVD, the risk of CVD mortality was elevated among both non-diabetic women with CVD (HR=1.82, CI: 1.60-2.07, P<0.001) and diabetic women without prior CVD (HR=2.24, CI: 1.87-2.69, P<0.001). CVD mortality was highest among diabetic women with CVD (HR=3.41, CI: 2.61-4.45, P<0.001). Compared to non-diabetic women with CVD, diabetic women without prior CVD had a significantly higher adjusted HR for total and CVD mortality (P<0.001 and P<0.05 respectively). CHD mortality did not differ significantly between non-diabetic women with CVD and diabetic women without prior CVD. CONCLUSION: Older diabetic women without prior CVD have a higher risk of all-cause and CVD mortality and a similar risk of CHD mortality compared to non-diabetic women with pre-existing CVD. For older women, these data support the equivalence of prior CVD and diabetes mellitus in current guidelines for the prevention of CVD.

Reproductive and post-reproductive life history of wild-caught Drosophila melanogaster under laboratory conditions.

The life history of the fruit fly (Drosophila melanogaster) is well understood, but fitness components are rarely measured by following single individuals over their lifetime, thereby limiting insights into lifetime reproductive success, reproductive senescence and post-reproductive lifespan. Moreover, most studies have examined long-established laboratory strains rather than freshly caught individuals and may thus be confounded by adaptation to laboratory culture, inbreeding or mutation accumulation. Here, we have followed the life histories of individual females from three recently caught, non-laboratory-adapted wild populations of D. melanogaster. Populations varied in a number of life-history traits, including ovariole number, fecundity, hatchability and lifespan. To describe individual patterns of age-specific fecundity, we developed a new model that allowed us to distinguish four phases during a female's life: a phase of reproductive maturation, followed by a period of linear and then exponential decline in fecundity and, finally, a post-ovipository period. Individual females exhibited clear-cut fecundity peaks, which contrasts with previous analyses, and post-peak levels of fecundity declined independently of how long females lived. Notably, females had a pronounced post-reproductive lifespan, which on average made up 40% of total lifespan. Post-reproductive lifespan did not differ among populations and was not correlated with reproductive fitness components, supporting the hypothesis that this period is a highly variable, random 'add-on' at the end of reproductive life rather than a correlate of selection on reproductive fitness. Most life-history traits were positively correlated, a pattern that might be due to genotype by environment interactions when wild flies are brought into a novel laboratory environment but that is unlikely explained by inbreeding or positive mutational covariance caused by mutation accumulation.