Heritable Variation In Fitness Research Articles

A Chemostat Model for Evolution by Persistence: Clade Selection and Its Explanatory Autonomy

AbstractMany contemporary biologists and philosophers of biology admit that selection occurs at any level of the biological hierarchy at which entities showing heritable variation in fitness are found, while insisting that fitness at any level entails differential reproduction, not differential persistence. Those who allow that persistence can be selected doubt that selection on nonreproducing entities can be reiterated, to produce “complex adaptations.” We present here a verbal model of subclones evolving in a simple idealized chemostat that calls into question these suppositions and is usefully explanatory when taken as an analogy to selection for persistence of clades.

Natural Selection beyond Life? A Workshop Report.

Natural selection is commonly seen not just as an explanation for adaptive evolution, but as the inevitable consequence of “heritable variation in fitness among individuals”. Although it remains embedded in biological concepts, such a formalisation makes it tempting to explore whether this precondition may be met not only in life as we know it, but also in other physical systems. This would imply that these systems are subject to natural selection and may perhaps be investigated in a biological framework, where properties are typically examined in light of their putative functions. Here we relate the major questions that were debated during a three-day workshop devoted to discussing whether natural selection may take place in non-living physical systems. We start this report with a brief overview of research fields dealing with “life-like” or “proto-biotic” systems, where mimicking evolution by natural selection in test tubes stands as a major objective. We contend the challenge may be as much conceptual as technical. Taking the problem from a physical angle, we then discuss the framework of dissipative structures. Although life is viewed in this context as a particular case within a larger ensemble of physical phenomena, this approach does not provide general principles from which natural selection can be derived. Turning back to evolutionary biology, we ask to what extent the most general formulations of the necessary conditions or signatures of natural selection may be applicable beyond biology. In our view, such a cross-disciplinary jump is impeded by reliance on individuality as a central yet implicit and loosely defined concept. Overall, these discussions thus lead us to conjecture that understanding, in physico-chemical terms, how individuality emerges and how it can be recognised, will be essential in the search for instances of evolution by natural selection outside of living systems.

Proximate Causes of Infertility and Embryo Mortality in Captive Zebra Finches.

AbstractSome species show high rates of reproductive failure, which is puzzling because natural selection works against such failure in every generation. Hatching failure is common in both captive and wild zebra finches (Taeniopygia guttata), yet little is known about its proximate causes. Here we analyze data on reproductive performance (the fate of >23,000 eggs) based on up to 14 years of breeding of four captive zebra finch populations. We find that virtually all aspects of reproductive performance are negatively affected by inbreeding (mean ); by an early-starting, age-related decline (mean ); and by poor early-life nutrition (mean ). However, these effects together explain only about 3% of the variance in infertility, offspring mortality, fecundity, and fitness. In contrast, individual repeatability of different fitness components varied between 15% and 50%. As expected, we found relatively low heritability in fitness components (median: 7% of phenotypic variation and 29% of individually repeatable variation). Yet some of the heritable variation in fitness appears to be maintained by antagonistic pleiotropy (negative genetic correlations) between male fitness traits and female and offspring fitness traits. The large amount of unexplained variation suggests a potentially important role of local dominance and epistasis, including the possibility of segregating genetic incompatibilities.

Estimating the genome-wide contribution of selection to temporal allele frequency change

Rapid phenotypic adaptation is often observed in natural populations and selection experiments. However, detecting the genome-wide impact of this selection is difficult since adaptation often proceeds from standing variation and selection on polygenic traits, both of which may leave faint genomic signals indistinguishable from a noisy background of genetic drift. One promising signal comes from the genome-wide covariance between allele frequency changes observable from temporal genomic data (e.g., evolve-and-resequence studies). These temporal covariances reflect how heritable fitness variation in the population leads changes in allele frequencies at one time point to be predictive of the changes at later time points, as alleles are indirectly selected due to remaining associations with selected alleles. Since genetic drift does not lead to temporal covariance, we can use these covariances to estimate what fraction of the variation in allele frequency change through time is driven by linked selection. Here, we reanalyze three selection experiments to quantify the effects of linked selection over short timescales using covariance among time points and across replicates. We estimate that at least 17 to 37% of allele frequency change is driven by selection in these experiments. Against this background of positive genome-wide temporal covariances, we also identify signals of negative temporal covariance corresponding to reversals in the direction of selection for a reasonable proportion of loci over the time course of a selection experiment. Overall, we find that in the three studies we analyzed, linked selection has a large impact on short-term allele frequency dynamics that is readily distinguishable from genetic drift.

Group and individual selection during evolutionary transitions in individuality: meanings and partitions.

The Price equation embodies the 'conditions approach' to evolution in which the Darwinian conditions of heritable variation in fitness are represented in equation form. The equation can be applied recursively, leading to a partition of selection at the group and individual levels. After reviewing the well-known issues with the Price partition, as well as issues with a partition based on contextual analysis, we summarize a partition of group and individual selection based on counterfactual fitness, the fitness that grouped cells would have were they solitary. To understand 'group selection' in multi-level selection models, we assume that only group selection can make cells suboptimal when they are removed from the group. Our analyses suggest that there are at least three kinds of selection that can be occurring at the same time: group-specific selection along with two kinds of individual selection, within-group selection and global individual selection. Analyses based on counterfactual fitness allow us to specify how close a group is to being a pseudo-group, and this can be a basis for quantifying progression through an evolutionary transition in individuality (ETI). During an ETI, fitnesses at the two levels, group and individual, become decoupled, in the sense that fitness in a group may be quite high, even as counterfactual fitness goes to zero. This article is part of the theme issue 'Fifty years of the Price equation'.

Offspring phenotype is shaped by the nonsperm fraction of semen.

In a large majority of animal species, the only contribution of males to the next generation has been assumed to be their genes (sperm). However, along with sperm, seminal plasma contains a wide array of extracellular factors that have many important functions in reproduction. Yet, the potential intergenerational effects of these factors are virtually unknown. We investigated these effects in European whitefish (Coregonus lavaretus) by experimentally manipulating the presence and identity of seminal plasma and by fertilizing the eggs of multiple females with the manipulated and unmanipulated semen of several males in a full-factorial breeding design. The presence of both own seminal plasma and foreign seminal plasma inhibited sperm motility, and the removal of own seminal plasma decreased embryo survival. Embryos hatched significantly earlier after both semen manipulations than in control fertilizations; foreign seminal plasma also increased offspring aerobic swimming performance. Given that our experimental design allowed us to control potentially confounding sperm-mediated (sire) effects and maternal effects, our results indicate that seminal plasma may have direct intergenerational consequences for offspring phenotype and performance. This novel source of offspring phenotypic variance may provide new insights into the evolution of polyandry and mechanisms that maintain heritable variation in fitness and associated female mating preferences.

Genome-wide sexually antagonistic variants reveal long-standing constraints on sexual dimorphism in fruit flies.

The evolution of sexual dimorphism is constrained by a shared genome, leading to ‘sexual antagonism’, in which different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, we know little about the identity, genomic location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual antagonism. We identify approximately 230 chromosomal clusters of candidate antagonistic single nucleotide polymorphisms (SNPs). In contradiction to classic theory, we find no clear evidence that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations and closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million years) genomic constraints on the evolution of sexual dimorphism. Based on our results, we propose that antagonistic variation accumulates because of constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation.

Heterogeneity in individual quality in birds: overall patterns and insights from a study on common terns

While life‐history theory predicts a tradeoff between reproduction and survival, positive covariance, indicative of heterogeneity in individual quality, is often reported among individuals from natural populations. We review longitudinal studies of wild bird populations that test the relationship between annual reproductive success and lifespan and find the majority to report a positive correlation, while none reports a negative correlation. Heterogeneity in individual quality in resource acquisition, masking resource‐based tradeoffs, therefore appears to be common in birds. Considering that there is little evidence for heritable variation in fitness, heterogeneity in individual quality among adults may be due to life‐long effects of developmental conditions. In a 20‐year case study on common terns Sterna hirundo, we test for life‐long effects of cohort quality and within‐cohort nest quality, but find no significant effects on long‐term proxies of quality. Since other studies do find strong life‐long effects of developmental conditions, we suggest that the brood reduction strategy adopted by common terns, causing the majority of offspring to die rapidly after hatching, efficiently reduces variation in offspring quality at independence. As such, a brood reduction strategy may contribute to reduced heterogeneity in adult survival in stochastic environments, both suggested to be more common and adaptive in long‐lived species. Further study is required to assess heterogeneity in individual reproduction, especially in relation to environmental stochasticity and species’ life‐history strategies, in order to assess whether the relative strength of selection in early and late life may indeed affect the magnitude of heterogeneity in individual quality over life, and how this is mediated by parent–offspring conflict.

An epigenetic resolution of the lek paradox.

Female choice for traits signaling male genetic quality is expected to erode heritable variation in fitness, undermining the benefits of choice. Known as the lek paradox, this contradiction has motivated extensive population genetic theory, yet remains unresolved. Recent modeling by Bonduriansky and Day concludes that costly female preference is best maintained when male condition is determined by environmentally induced factors transmitted across single generations. Here, we reformulate their model in explicitly epigenetic terms, and review evidence that environmentally induced paternal effects are mediated through epigenetic changes in sperm. Noncoding RNA expression, DNA methylation and histone modifications are highly sensitive to diet, stress, toxicants and stochastic events. Epigenetic variation renews each generation and cannot be exhausted by selection. By choosing well-endowed males that produce gametes in epigenetically good states, females can increase their fitness directly through increased fertilization success or indirectly through epigenetic effects on the fitness of offspring and potentially subsequent generations. Also watch the video abstract.

Sexual Selection and Mate Choice: Insights from Neutralist Perspectives

Darwin’s concept of sexual selection has been an area of intense research interest for the past half-century. Research has mainly focused on intersexual selection (selection arising from mate choice), and has particularly focused on the hypothesis that mates are chosen on the basis of “genetic quality” which is “honestly” signaled by sexually dimorphic traits. I discuss these models in the light of evidence that most genetic variation in real populations is either selectively neutral or slightly deleterious. Since several well-known models have focused on the immune system as a source of heritable variation in fitness, I examine evidence from studies of the vertebrate major histocompatibility complex and its interaction with pathogens. Finally, I discuss alternative hypotheses for the evolution of secondary sexual characteristics that are consistent with the prevalence of purifying selection rather than positive selection in most populations. One such model, the random walk model, relies only on the well-attested processes of mutation, purifying selection, and genetic drift, thereby providing an attractive alternative to models that assume ubiquitous positive selection.

Cytochrome P450 gene CYP337 and heritability of fitness traits in the Glanville fritillary butterfly

Fitness-related life history traits often show substantial heritable genetic variation in natural populations, but knowledge of the genetic architecture of these traits is limited. In the Glanville fritillary butterfly, we measured the heritability of key life history traits in a large outdoor population cage during 2 years and generations and combined this experiment with an association study of a set of candidate genes. The genes were selected on the basis of previous genomic and transcriptomic studies and have been linked to the physiology and life history of this or other arthropod species. Heritability was high and significant for two traits, post-diapause larval development time (h(2) = 0.37) and lifetime egg (and larval) production (h(2) = 0.62); the latter is closely related to lifetime reproductive success and therefore fitness. We discovered a strong association between genetic polymorphism in the cytochrome P450 gene CYP337 and lifetime egg production, which accounted for 14% of the additive variance in egg production. This gene belongs to a group of cytochrome P450 genes that have a well-documented role in host plant adaptations in Lepidoptera and other insects and is likely to play an important role in the ecology and microevolution of the Glanville fritillary. This study provides a prime example of a gene associated with heritable fitness variation, measured under semi-natural ecological conditions.

A New Definition of Aging?

I do not fundamentally differ with Michael Rose's definition of aging and his thesis. For him aging is defined as a decline or loss (a “de-tuning”) of adaptation with increasing age, caused by a time-progressive decline of Hamilton's forces of natural selection. To my mind, this definition is consistent with most previous definitions of aging used by the majority of evolutionary biologists. Most evolutionary biologists define aging as an age-dependent or age-progressive decline in intrinsic physiological function, leading to an increase in age-specific mortality rate (i.e., a decrease in survival rate) and a decrease in age-specific reproductive rate (e.g., Medawar, 1955; Williams, 1957; Rose, 1991; Partridge and Barton, 1996; Tatar, 2001; Promislow and Bronikowski, 2006; Flatt and Schmidt, 2009; Bronikowski and Flatt, 2010; Fabian and Flatt, 2011). Rose (1991), for example, in his seminal book on the evolution of aging defines aging as “a persistent decline in the age-specific fitness components of an organism due to internal physiological degeneration.” At level of the individual, the intrinsic physiological state at a specific age determines, among other things, whether an individual is dead or alive and how much it reproduces. At the level of the cohort, the underlying physiological states of the individuals translate into the age-specific rates of mortality and reproduction. We therefore diagnose demographic aging to occur if we observe an increase in age-specific mortality and a decrease in age-specific reproductive rate in the cohort (e.g., Bronikowski and Flatt, 2010). In particular, the notion that aging is a de-tuning of adaptation is completely consistent with the standard definition of aging. Adaptation by natural selection is based on heritable variation in fitness among individuals, and survival and reproduction are the most important determinants or components of fitness (e.g., Stearns, 1992). Thus, in agreement with Rose's definition, the age-dependent decline of age-specific survival and reproductive rates represents an age-progressive loss or de-tuning of fitness or the state of adaptation. Moreover, it is well-accepted among evolutionary biologists that this decline is due to the declining forces of natural selection with increasing age. So where exactly do Rose's definition and main thesis differ from the standard definition of aging? The crux of Rose's thesis is not so much about the fact that adaptation and the forces of selection decline but about the fact that the forces plateau (Rose et al., 2007). Although this is well-known from both theory and data, the important point is that, under protected conditions (low extrinsic mortality), age-specific mortality and fecundity also exhibit plateaus late in life. This means that the age-specific rates of survival and reproduction do not necessarily decrease to zero toward the end of life, as had previously (mostly implicitly yet incorrectly) been assumed. In fact, the existence of such plateaus has often been missed because observing them requires very large cohort sizes. The work by Rose and others now posits that these late life mortality and fecundity plateaus are a direct, causal consequence of the plateaus in the forces of selection. The real issue at stake is therefore that the aging process is not sufficiently well defined if we describe it as a persistent age-progressive decline of physiological function leading to a steady age-progressive decline in survival and reproduction. Instead, demographic aging involves an age-progressive decline in survival and reproduction which is often (perhaps always) being followed by plateaus in the rates of mortality and reproduction. In other words, the age-dependent decline that is characteristic of the aging process is therefore not (at least not necessarily) persistent and steady but levels off. Note Rose's (1991) use of the word “persistent” in his classical definition of aging quoted above; clearly, in view of the by now well-documented demographic cessation of aging at advanced ages and under protected conditions, the usage of the term “persistent” is problematic. However, this being said, it should be pointed out that most evolutionary biologists do not include terms such as “persistent” or “steady” in their definitions of aging: most of them simply characterize demographic aging as an age-progressive increase in mortality rate and a decrease in reproductive rate. From my point of view, such a definition of aging is certainly not wrong, but one might say that it is not sufficiently precise. Obviously, in any finite cohort of individuals, the age-specific rates of survival and reproduction will eventually reach zero at some point of time: everyone has died and stopped reproducing. Thus, survival and reproduction do decline to zero levels in a time-progressive manner. However, as the existence of plateaus demonstrates, it would be wrong to assume that these rates decline steadily toward zero. If it turns out that such plateaus are general under benign conditions (the evidence so far suggests that they might be), then their existence must be integrated into the standard definition of the aging process. Similar considerations apply when we talk about the age-progressive decline of physiological function. We might still say that demographic aging at the cohort level reflects the age-dependent decline or deterioration of physiological function of the individuals in the cohort; however, we should not take this to mean that physiological function deteriorates steadily toward zero functionality. In a finite population with individuals of finite lifespan, physiological functionality will be zero at some point; however, before this point is reached, it might plateau. Although we still know next to nothing about the mechanistic details of physiology during late life, the plateauing of physiological decline might be a direct consequence of the plateaus of Hamilton's forces of natural selection. Thus, if Rose's model is correct, plateaus in the forces of selection cause plateaus in individual physiological state which in turn cause plateaus in mortality and reproduction. The notion that Hamiltons’ forces of natural selection plateau thus has major implications for our understanding of the aging process and, in particular, of late life: at advanced ages natural selection is unable to distinguish among individuals, be it at the level of physiological state or at the level of fitness components, so that demographic aging, under benign conditions, can come to a halt. While it remains to be seen how general the existence of such plateaus is across species, and although more theoretical and empirical efforts are required to fully understand the nature of the demographic cessation of aging, the phenomenon itself is now empirically well established.

Good Genes and Sexual Selection in Dung Beetles (Onthophagus taurus): Genetic Variance in Egg-to-Adult and Adult Viability

Whether species exhibit significant heritable variation in fitness is central for sexual selection. According to good genes models there must be genetic variation in males leading to variation in offspring fitness if females are to obtain genetic benefits from exercising mate preferences, or by mating multiply. However, sexual selection based on genetic benefits is controversial, and there is limited unambiguous support for the notion that choosy or polyandrous females can increase the chances of producing offspring with high viability. Here we examine the levels of additive genetic variance in two fitness components in the dung beetle Onthophagus taurus. We found significant sire effects on egg-to-adult viability and on son, but not daughter, survival to sexual maturity, as well as moderate coefficients of additive variance in these traits. Moreover, we do not find evidence for sexual antagonism influencing genetic variation for fitness. Our results are consistent with good genes sexual selection, and suggest that both pre- and postcopulatory mate choice, and male competition could provide indirect benefits to females.

Evolution of intra-ejaculate sperm interactions: do sperm cooperate?

Sperm are often considered to be individuals, in part because of their unique genetic identities produced as a result of synapsis during meiosis, and in part due to their unique ecology, being ejected away from the soma to continue their existence in a foreign environment. Selection at the level of individual sperm has been suggested to explain the evolution of two enigmatic sperm phenotypes: sperm heteromorphism, where more than one type of sperm is produced by a male, and sperm conjugation, where multiple sperm join together for motility and transport through the female reproductive tract before dissociation prior to fertilization. In sperm heteromorphic species, only one of the sperm morphs typically participates in fertilization, with the non-fertilizing "parasperm" being interpreted as reproductive altruists. Likewise, in species with sperm conjugation, high levels of sperm mortality have been suggested to be required for conjugate break-up and this has been considered evidence of kin-selected altruism. However, it is unclear if sperm possess the heritable variation in fitness (i.e. are individuals) required for the evolution of cooperation. We investigate the question of sperm individuality by focusing on how sperm morphology is determined and how sperm conjugates are formed. Concentrating on sperm conjugation, we discuss functional hypotheses for the evolutionary maintenance of this remarkable trait. Additionally, we speculate on the potential origins of sperm heteromorphism and conjugation, and explore the diversification and losses of these traits once they have arisen in a lineage. We find current evidence insufficient to support the concept of sperm control over their form or function. Thus, without additional evidence of haploid selection (i.e. sperm phenotypes that reflect their haploid genome and result in heritable differences in fitness), sperm heteromorphism and conjugation should be interpreted not as cooperation but rather as traits selected at the level of the male, much like other ejaculatory traits such as accessory gland proteins and ejaculate size.

A Continuous-State Coalescent and the Impact of Weak Selection on the Structure of Gene Genealogies

Coalescent theory provides an elegant and powerful method for understanding the shape of gene genealogies and resulting patterns of genetic diversity. However, the coalescent does not naturally accommodate the effects of heritable variation in fitness. Although some methods are available for studying the effects of strong selection (Ns >> 1), few tools beyond forward simulation are available for quantifying the impact of weak selection at many sites. Here, we introduce a continuous-state coalescent capable of accurately describing the distortions to genealogies caused by moderate to weak natural selection affecting many linked sites. We calculate approximately the full distribution of pairwise coalescent times, the lengths of coalescent intervals, and the time to the most recent common ancestor of a sample. Weak selection (Ns approximately 1) is found to substantially decrease the tree depth, primarily through a shortening of the lengths of the basal coalescent intervals. Additionally, we demonstrate that only two parameters, population size and the variance of the distribution describing fitness heritability, are sufficient to describe most changes.

Genetic recombination and adaptation to fluctuating environments: selection for geotaxis in Drosophila melanogaster.

Heritable variation in fitness is the fuel of adaptive evolution, and sex can generate new adaptive combinations of alleles. If the generation of beneficial combinations drives the evolution of recombination, then the level of recombination should result in changes in the response to selection. Three types of lines of Drosophila melanogaster varying in their level of genetic recombination were selected over 38 generations for geotaxis. The within-chromosome recombination level of these lines was controlled for 60% of the genome: chromosome X and chromosome II. The full recombination lines had normal, unmanipulated levels of recombination on these two chromosomes. Conversely, nonrecombination lines had recombination effectively eliminated within the X and second chromosomes. Finally, partial recombination lines had the effective rate of within-chromosome recombination lowered to 10% of natural levels for these two chromosomes. The rate of response to selection was measured for continuous negative geotaxis and for a fluctuating environment (alternating selection for negative and positive geotaxis). All selected Drosophila lines responded to selection and approximately 36% of the response to selection was because of the X and second chromosomes. However, recombination did not accelerate adaptation during either directional or fluctuating selection for geotaxis.

On the Reorganization of Fitness During Evolutionary Transitions in Individuality

The basic problem in an evolutionary transition is to understand how a group of individuals becomes a new kind of individual, possessing the property of heritable variation in fitness at the new level of organization. During an evolutionary transition, for example, from single cells to multicellular organisms, the new higher-level evolutionary unit (multicellular organism) gains its emergent properties by virtue of the interactions among lower-level units (cells). We see the formation of cooperative interactions among lower-level units as a necessary step in evolutionary transitions; only cooperation transfers fitness from lower levels (costs to group members) to higher levels (benefits to the group). As cooperation creates new levels of fitness, it creates the opportunity for conflict between levels as deleterious mutants arise and spread within the group. Fundamental to the emergence of a new higher-level unit is the mediation of conflict among lower-level units in favor of the higher-level unit. The acquisition of heritable variation in fitness at the new level, via conflict mediation, requires the reorganization of the basic components of fitness (survival and reproduction) and life-properties (such as immortality and totipotency) as well as the co-option of lower-level processes for new functions at the higher level. The way in which the conflicts associated with the transition in individuality have been mediated, and fitness and general life-traits have been re-organized, can influence the potential for further evolution (i.e., evolvability) of the newly emerged evolutionary individual. We use the volvocalean green algal group as a model-system to understand evolutionary transitions in individuality and to apply and test the theoretical principles presented above. Lastly, we discuss how the different notions of individuality stem from the basic properties of fitness in a multilevel selection context.

Effective size of populations with heritable variation in fitness.

The effective size of monogamous populations with heritable variation in fitness is formulated, and the expression obtained is compared with a published equation. It is shown that the published equation for dioecious populations is inappropriate for most animal and human populations, because the derivation is implicitly based on the assumption that zygotes are produced by random union of gametes, each from conceptual male and female gametic pools. A convenient equation for practical use is proposed, and the application is illustrated with the estimation of the effective size of a rural human community in Japan.

Effective population size

What is it? An aid to calculation in population genetics, introduced by Sewall Wright. The rate of change of the genetic make-up of a population by genetic drift – fluctuations in allele frequencies caused by random sampling – is inversely related to the effective population size, Ne. Ne is measured with reference to an ideal ‘Wright–Fisher’ population. This has a fixed number of N diploid breeding individuals, with no distinction of sex. Each new generation is formed by sampling genes randomly from the parents of the previous generation. The rate at which selectively neutral variability is lost from the population is then equal to 1/(2N). In the messier real world, there may be two different sexes, population size may change, individuals may differ in their reproductive success and there may be overlapping generations. If you are clever enough, you can write down an expression for the rate of drift per generation in such cases. This is then equated to 1/(2Ne). Ne is usually substantially smaller than the census number of breeding individuals.Why is it useful? Genetic drift is a major factor in DNA sequence evolution. To make sense of the data, we need evolutionary models which include genetic drift. By plugging Ne into the relevant equations, we can write down general expressions, instead of having to work out new results for each type of population. For example, a favourable new mutation which increases the fitness of its carriers by a small amount s has a chance of spreading of 2(Ne/N)s in a population of size N and effective size Ne. Reducing Ne relative to N thus reduces the chance that a favourable mutation will spread.Similarly, the chance that a deleterious mutation can get fixed against selection is increased by a reduction in Ne, and approaches the value for a neutral mutation when |Nes|⪡1. The equilibrium level of within-population variability for neutral or nearly-neutral variants is controlled by the product of the mutation rate and Ne, so that Ne plays an important role in the interpretation of data on single nucleotide polymorphisms, a major focus of contemporary human genetics.What influences Ne? If population size changes, the long-term value of Ne, which controls the level of neutral variability, is the harmonic mean (reciprocal of the mean of the reciprocals) of the series of values for each generation. A population that has recently expanded, like our own, has a much smaller Ne than indicated by its current size. In the human case, levels of variability indicate that Ne is close to 10,000, reflecting the population size in the remote past. Ne is affected by mode of inheritance, so that X-linked, Y-linked and organelle genes each have their own Ne values, which differ from that for autosomal genes. Ne is also influenced by natural or artificial selection, which induce heritable variation in fitness. Selection at sites linked to a gene under study may greatly reduce its Ne value. This means that genomic regions with low levels of genetic recombination, where genes tend to be tightly linked to each other, may have lower than average levels of variability and adaptation.

Signaling Health versus Parasites

The Hamilton-Zuk hypothesis, that parasite-host coevolution can maintain heritable variation in fitness, has inspired a very successful research program on sexual selection on signals of health. The immunocompetence handicap hypothesis was developed to provide a handicapping mechanism to stabilize the correlation between signals and health. In earlier articles, I showed that handicap signaling is a special case, not a general law that we can rely on to deduce relative costs across signalers of different quality at equilibrium. The essential requirement for reliable signaling is that higher-quality signalers are more efficient; they get greater marginal fitness returns from an incremental increase in the signal. This does not undermine the Hamilton-Zuk hypothesis or the immunocompetence mechanism, but it does raise doubts about a widespread assumption that is commonly used to test these hypotheses: that sexual selection on signals of health implies the choice of mates with the fewest parasites. Immunity and parasites might play a fundamental role in many biological signaling systems, but viability-indicating traits are not necessarily parasite-load-indicating traits. Theory allows for the possibility that high-quality big signalers have greater health and more parasites than low-quality small signalers (and the data suggest that in many systems they do). This means that we cannot test the Hamilton-Zuk hypothesis or the immunocompetence handicap hypothesis by counting parasites. More generally, we cannot understand sexual selection on signals of health by focusing on the viability costs of signals.