Predicting the future of our oceans-Evaluating genomic forecasting approaches in marine species.

Climate change is restructuring biodiversity on multiple scales and there is a pressing need to understand the downstream ecological and genomic consequences of this change. Recent advancements in the field of eco-evolutionary genomics have sought to include evolutionary processes in forecasting species' responses to climate change (e.g., genomic offset), but to date, much of this work has focused on terrestrial species. Coastal and offshore species, and the fisheries they support, may be even more vulnerable to climate change than their terrestrial counterparts, warranting a critical appraisal of these approaches in marine systems. First, we synthesize knowledge about the genomic basis of adaptation in marine species, and then we discuss the few examples where genomic forecasting has been applied in marine systems. Next, we identify the key challenges in validating genomic offset estimates in marine species, and we advocate for the inclusion of historical sampling data and hindcasting in the validation phase. Lastly, we describe a workflow to guide marine managers in incorporating these predictions into the decision-making process.

Quantifying heritable variation in fitness-related traits of wild, farmed and hybrid Atlantic salmon families in a wild river environment.

Farmed fish are typically genetically different from wild conspecifics. Escapees from fish farms may contribute one-way gene flow from farm to wild gene pools, which can depress population productivity, dilute local adaptations and disrupt coadapted gene complexes. Here, we reanalyse data from two experiments (McGinnity et al., 1997, 2003) where performance of Atlantic salmon (Salmo salar) progeny originating from experimental crosses between farm and wild parents (in three different cohorts) were measured in a natural stream under common garden conditions. Previous published analyses focussed on group-level differences but did not account for pedigree structure, as we do here using modern mixed-effect models. Offspring with one or two farm parents exhibited poorer survival in their first and second year of life compared with those with two wild parents and these group-level inferences were robust to excluding outlier families. Variation in performance among farm, hybrid and wild families was generally similar in magnitude. Farm offspring were generally larger at all life stages examined than wild offspring, but the differences were moderate (5-20%) and similar in magnitude in the wild versus hatchery environments. Quantitative genetic analyses conducted using a Bayesian framework revealed moderate heritability in juvenile fork length and mass and positive genetic correlations (>0.85) between these morphological traits. Our study confirms (using more rigorous statistical techniques) previous studies showing that offspring of wild fish invariably have higher fitness and contributes fresh insights into family-level variation in performance of farm, wild and hybrid Atlantic salmon families in the wild. It also adds to a small, but growing, number of studies that estimate key evolutionary parameters in wild salmonid populations. Such information is vital in modelling the impacts of introgression by escaped farm salmon.

Longitudinal bio-logging reveals interplay between extrinsic and intrinsic carry-over effects in a long-lived vertebrate.

Carry-over effects have major implications for individual fitness and population and evolutionary dynamics. The strength of these effects is dependent on an individual's intrinsic performance and the environmental conditions it experiences. However, understanding the relative importance of environmental and intrinsic effects underpinning seasonal interactions has proved extremely challenging, since they covary. A powerful approach is longitudinal measurement of individuals across a range of conditions, whereby each animal is effectively acting as its own control. We related time spent foraging during the nonbreeding period to subsequent breeding performance in European Shags Phalacrocorax aristotelis. By following individuals for up to six years, we could test simultaneously for extrinsic and intrinsic effects using random regression modeling. We detected significant annual and among-individual variation in daily foraging time during the late winter, and clear variation among individuals in the quadratic relationship between foraging time and date. Shorter foraging times were associated with earlier and more successful breeding, driven by differences among years and individuals, with no evidence of individual variation in the slope of these relationships. That both environmental and intrinsic variation shape carry-over effects has important implications for population responses to environmental change.

Lake-specific variation in growth, migration timing and survival of juvenile sockeye salmon Oncorhynchus nerka: separating environmental from genetic influences.

Time series on juvenile life-history traits obtained from sockeye salmon Oncorhynchus nerka were analysed to assess lake-specific environmental influences on juvenile migration timing, size and survival of fish from a common gene pool. Every year for the past two decades, O. nerka have been spawned at a hatchery facility, and the progeny released into two lakes that differ in average summer temperatures, limnological attributes and growth opportunities. Juveniles reared in the warmer, more productive Crosswind Lake were larger and heavier as smolts compared to those from the cooler, less productive Summit Lake and had higher in-lake and subsequent marine survival. Crosswind Lake smolts migrated from the lake to sea slightly earlier in the season but the migration timing distributions overlapped considerably across years. Fry stocking density had a negative effect on smolt length for both lakes, and a negative effect on in-lake survival in Summit Lake. Taken together, the results revealed a strong effect of lake-rearing environment on the expression of life-history variation in O. nerka. The stocking of these lakes each year with juveniles from a single mixed-source population provided a large-scale reverse common-garden experiment, where the same gene pool was exposed to different environments, rather than the different gene pools in the same environment approach typical of evolutionary ecology studies. Other researchers are encouraged to seek and exploit similar serendipitous situations, which might allow environmental and genetic influences on ecologically important traits to be distinguished in natural or semi-natural settings.

Decline in cognitive performance in aging twins. Heritability and biobehavioral predictors from the National Heart, Lung, and Blood Institute Twin Study.

The present study examined the contribution of genetic factors to Digit Symbol performance and its decline in 23 monozygotic twin pairs (mean age at examination 1, 57.1 years) and 21 dizygotic twin pairs (mean age at examination 1, 56.3 years). These men were assessed twice during a 5-year interval as part of the National Heart, Lung, and Blood Institute Twin Study. The prevalence of decline (a change, greater than 1 SD) during the 5-year interval was 35% and 39% for monozygotic and dizygotic twins, respectively. The pairwise concordance for decline was 45% in monozygotic and 8% in dizygotic twin pairs, suggesting a possible role for genetic factors in the decline in Digit Symbol performance in this sample. A comparison of baseline biologic and behavioral characteristics within monozygotic twin pairs discordant for decline in Digit Symbol performance revealed that decliners had higher initial systolic blood pressures, lower serum cholesterol levels, and lower heart rates than nondecliners.

Marked individual variability in heart rate "normalization" by ethanol.

In order to test Kissin's (1974) concept of "normalization" by ethanol (deviant prealcohol parameter values becoming less deviant after alcohol) in nonalcoholics, data on unselected mice and nonalcoholic humans were analyzed. These data were on heart rates (HR) of 1055 HS mice and 24 young adults, measured before and after receiving a dose of ethanol (mice: 1.4g/kg, i.p.;humans: 1.3g/kg, oral). Both mice and humans, on the average, show marked "normalization" inintially low HR usually increasing after alcohol, and initially high HR usually decreasing. The correlation between (1) deviation in HR from the prealcohol mean and (2) change in HR after alcohol was -0.803 for mice and -0.538 for humans. There is very great individual variability, however, in the degree of this normalizing response, some individuals normalizing strongly and others not at all. Although first described in alcoholics, strong normalization by alcohol of several psychophysiological parameters is now known to occur in mice and seems likely to occur in some nonalcoholic humans. The possible relevance of these results to predisposition to alcoholism remains to be shown.

Confirmation of an abnormal (non-Poisson) distribution of sperm from some infertile men in the hamster-ovum test.

The present study was carried out to investigate an earlier report that stated that some men of infertile couples (patients), but not normal donors, have an abnormal (non-Poison) distribution of penetrating sperm among ova in the hamster-ovum test. Semen samples from 60 men, 24 proven fathers and 36 patients, were analyzed for agreement with the theoretical Poisson distribution (PD). Most of the fathers (23 of 24) fit PD well, but 10 of the patients did not. The overall (group) fit of fathers is good, but that of the patients is poor. Patients, but not fathers, are heterogeneous in their agreement with PD; about 25% fit poorly whereas more than 50% fit well. The 25% fitting poorly may often be those patients who are truly infertile (even when their wives are actually fertile).

Detection of benzo(a)pyrene diol epoxide-DNA adducts in sperm of men exposed to cigarette smoke.

OBJECTIVE: To determine whether the adducts formed when benzo(a)pyrene, a diol epoxide derivative, binds covalently to DNA (BPDE-DNA adducts) are detectable in the sperm of men who smoke cigarettes. DESIGN: Prospective study. SETTING: The Toronto Hospital IVF-ET program. PATIENT(S): Twenty-three patients with normal seminal parameters: 11 smokers (20.6 +/- 0.7 cigarettes per day) and 12 nonsmokers. INTERVENTION(S): Semen samples obtained by masturbation. MAIN OUTCOME MEASURE(S): Seminal plasma samples were assessed for cotinine by RIA. Sperm were treated with dithiothreitol to release disulfide bonds and allow for DNA binding, then exposed to an anti-BPDE monoclonal antibody, a biotinylated antibody, and streptavidin-conjugated peroxidase. Staining intensity scores, determined in 100 cells per individual, were correlated with seminal plasma cotinine levels, a marker of smoking. RESULT(S): Cotinine levels correlated highly with the number of cigarettes smoked per day. Mean cotinine levels and mean staining intensity scores were higher in smokers than in nonsmokers. Staining intensity correlated highly with cotinine levels. CONCLUSION(S): We demonstrated, for the first time, that BPDE-DNA adducts in sperm cells are increased by smoking; we also detected comparatively high levels in nonsmokers, which indicates that environmental exposure also is substantial. The formation of adducts in spermatozoa is a potential source of transmissible prezygotic DNA damage.

Sperm from some infertile men may consist of several populations.

In the hamster ovum penetration (HOP) test, when ova have equal penetrability and sperm have equal penetrating ability, the distribution of zona-free hamster ova classified by number of penetrating human sperm is expected to follow the Poisson distribution (PD). This study reports tests for PD in HOP tests on 9 infertile patients and 11 normal controls. The data, presented in detail, show the expected PD in the control group. In contrast, 3 patients had HOP tests with definite non-PDs, whereas 5 patients have clearcut PDs. The cause of non-PD is unknown, but could result from differences among motile sperm in penetrating ability.

Cotinine, a major metabolite of nicotine, is detectable in follicular fluids of passive smokers in in vitro fertilization therapy.

OBJECTIVE: To assess cotinine, a metabolite of nicotine, in follicular fluids (FF) of women who smoke either actively or passively or not all. DESIGN: Controlled clinical study. SETTING: Infertile patients in a hospital IVF-ET program. PATIENTS: One hundred eleven women classified by smoking habits: active smokers (n = 44), passive smokers (n = 17), or nonsmokers (n = 50). INTERVENTIONS: Ovarian hyperstimulation. MAIN OUTCOME MEASURE: Cotinine levels in FF. RESULTS: A strong correlation between number of cigarettes smoked and levels of FF cotinine was found. The levels of FF cotinine were: active smokers 710.4 +/- 128.2, passive smokers 76.3 +/- 56.5, and nonsmokers 4.2 +/- 2.0 ng/mL (mean +/- SEM). The level in active smokers was significantly greater than in other groups. The levels of FF cotinine in passive smokers differed significantly from nonsmokers. Eighty-four percent of nonsmokers actually were exposed to nicotine, with a mean value of 5.0 ng/mL. CONCLUSIONS: Cotinine was detectable in a dose-dependent manner in active and passive smokers. It was detected in all active smokers and in a majority of passive smokers and self-reported nonsmokers. A strong interindividual variation suggests differences in metabolism and smoking habits. Follicular fluid cotinine assessments are useful for infertility studies.

Non-poisson distribution of sperm from grandfathers in zona-free hamster ova.

Earlier reports indicated that sperm from 25% of patients from infertile couples, but not from normal or fertile donors, show deviations from the theoretical Poisson distribution of the number of sperm penetrating zona-free hamster ova. Using semen samples from 15 grandfathers (aged 60 to 84 years) and 24 young fathers (aged 25 to 36 years), this study analyzed whether age also has an effect on the distribution. It was found that the overall fit to the Poisson distribution of the samples from grandfathers was very poor; in contrast, the samples from young fathers fit well. The observed deviations from the Poisson distribution among grandfathers may be a consequence of their long periods of sexual abstinence. Decrease in sexual activity produces age-different populations of sperm that probably differ in penetrating ability. Samples from older fathers also show a worse fit to the Poisson distribution than do those from younger fathers. These results suggest that the duration of sperm storage in the genital tract after maturation has an effect on sperm function.

Acute effects of ethanol in vivo on neuromuscular transmission.

The effects in vivo of acute doses of ethanol on impulse transmission in the region of the neuromuscular junction are poorly known. These effects were studied with a new procedure, using mouse tails in a constant temperature chamber to study the delay in nerve-to-muscle impulse transmission. A saline control and five ethanol doses (0.5, 1.0, 1.4, 2.0, 4.24 g/kg) were used with 96 mice. The interval ("residual latency", RL), between (a) the peak of the compound nerve action potential and (b) the first peak of the associated compound muscle action potential, was measured. Ethanol was given IP and tail nerve stimulations were done at 4 min intervals to 16 min post-ethanol. The mean pre-ethanol RL was 0.93 +/- 0.01 (SE) msec; about 25% of this time should be synaptic delay and the remainder is nerve and muscle fiber conduction time. Individual post-ethanol relative RL (RRL) values were calculated for each moue, based on its pre-ethanol value. With doses of 1.0 g/kg and higher there was a mean increase in RRL; at 16 min this increase was 0.8 to 4.4% (all p less than 0.01). At 0.5 g/kg, and also at higher doses, there was a significantly (p less than 0.01) increased variance in RRL 8 to 16 min post-ethanol. A marked correspondence between mean RRL and ataxia is apparent. This appears to be the first in vivo demonstration of acute effects of ethanol on neuromuscular transmission. The methods and mice used may comprise a useful animal model for detecting acute effects of low doses of ethanol on synaptic function.

The myth of "the average alcohol response".

The human alcohol response literature often states or implies that there is little variation among normal individuals in their responses to a standard dose. To test this assumption, a wide variety of alcohol responses was reviewed in studies where the original, individual responses were available. All such responses showed variability among individuals. Seven alcohol responses (individual changes from pre-alcohol baseline in heart rate, systolic and diastolic blood pressure, automobile driving ability, and three tests for intoxication) in normal males are analyzed in detail. Each response shows marked, significant individual variability. Genetic differences among individuals (in addition to environmental differences) are probably important in producing this variability. Since normal persons can vary greatly in their alcohol responses, it is not only incomplete but misleading to give only the mean value. Information on the range and frequency distribution of responses is also needed.