Genetic and evolutionary fitness.

The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness. Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions. Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved. Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationships, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases.     

Genetic and evolutionary fitness

The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness. Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions. Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved. Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationsips, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases.     

Quantitative genetic analysis of longitudinal trends in adoption designs with application to IQ in the Colorado Adoption Project

A factor model is presented that provides for either multivariate or developmental specification of longitudinal genetic and environmental effects in the presence of assortative mating and cultural transmission. Delta path methods are employed for the treatment of assortative mating and selective placement effects. The proportions of genetic and environmental variance and covariance attributable to assortative mating and cultural transmission are modeled explicitly. The model was applied to cognitive ability data on 493 families in the Colorado Adoption Project by means of maximum-likelihood pedigree analysis. A test of the assumption of multivariate normality of error provided an additional model criterion beyond the log-likelihood ratio statistic. No significant effects were found for cultural transmission, genetic-environmental covariance, or selective placement. The results suggest that the phenotypic stability of IQ during early childhood is largely, if not entirely, genetic in origin and that these longitudinal genetic effects can be represented most parsimoniously in the form of developmental transmission.     

Multivariate path analysis of specific cognitive abilities in the colorado adoption project

A multivariate path model of genetic and environmental transmission was fitted to specific cognitive abilities data (verbal, spatial, perceptual speed, and visual memory) and evaluated using a maximum-likelihood estimation procedure. In this first multivariate behavioral genetic analysis of adoption data, cultural transmission was modeled via parental phenotypes, each parental phenotype being allowed to affect all traits in the offspring, and assortative mating and cross-assortative mating were accommodated. Results of a preliminary analysis indicated that selective placement is absent in this study. When the full model was fitted to the data, it was found that assortative mating is more important than cross-assortative mating but is substantial only for verbal ability. Genetic transmission parameters are modest in size, whereas cultural transmission is both small and nonsignificant. A simplified model in which cultural transmission and genotype-environment correlation are constrained to be zero provided a good fit to the data. Analyses of the structures of genetic and environmental correlation matrices indicated a strong genetic general factor and a similar, but weaker, environmental factor. Inspection of the genetic transmission parameters suggests that genetic continuity between early childhood and adulthood may be substantial for verbal ability, spatial ability, and perceptual speed.This work was supported in part by grants from the NSF (BNS-7826204 and BNS-8200310) and from the NICHD (HD-10333).     

The host environment drives HIV-1 fitness

Viral fitness is defined by the ability of an individual genotype to produce infectious progeny in a specific environment. For HIV the environment is never constant but rather fluctuates in time and space. For instance, environmental factors that determine viral fitness during transmission from host to host are different to the pressures from either cytotoxic T-lymphocytes (CTLs) or antiviral drugs. Consequently, viral fitness is highly dependent on the environment and the accurate determination of this value therefore depends strongly on the chosen environmental setting. This review describes how the host environment imposes selective pressures on the virus that shape its genotype and fitness. The most important environments that the virus encounters throughout its life cycle and during natural infection are discussed. In order of appearance, CTLs are discussed, followed by neutralising antibodies and antiretroviral drug treatment. It then goes on to describe receptor molecules that mediate viral entry and intracellular restriction factors, which represent selective pressures that are present directly from the start of a natural infection. It concludes by discussing the complexity of viral fitness and how an accurate measure of viral fitness eventually may, for example, contribute to the improvement of antiretroviral therapy or help in the formulation of an optimal vaccination strategy.     

Genetic analysis of cleft lip with or without cleft palate in Madras, India.

We performed a genetic analysis of 331 non-syndromic cleft lip with or without cleft palate (CL +/- P) proband families ascertained in Madras, India. Predictions of the multifactorial threshold (MF/T) model are tested; goodness-of-fit tests of the MF/T model and complex segregation analysis are also utilized to clarify the genetic etiology of CL +/- P in this study population. There was little evidence for the MF/T model. The most reasonable conclusion from mixed model analysis is that of a major locus with reduced transmission probability. This is not altogether surprising if manifestation of CL +/- P also depends on in utero exposure to harmful environmental agents during the critical period of facial development, as suggested by Melnick et al. [1980] and demonstrated in an animal model of CL +/- P [Melnick et al., 1981]. Further the results in the Madras population are quite similar to those in other populations of Europe and Asia.     

The effects of cultural learning in populations of neural networks

Population learning can be described as the iterative Darwinian process of fitness-based selection and genetic transfer of information leading to populations of higher fitness and is often simulated using genetic algorithms. Cultural learning describes the process of information transfer between individuals in a population through non-genetic means. Cultural learning has been simulated by combining genetic algorithms and neural networks using a teacher-pupil scenario where highly fit individuals are selected as teachers and instruct the next generation. By examining the innate fitness of a population (i.e., the fitness of the population measured before any cultural learning takes place), it is possible to examine the effects of cultural learning on the population's genetic makeup. Our model explores the effect of cultural learning on a population and employs three benchmark sequential decision tasks as the evolutionary task for the population: connect-four, tic-tac-toe, and blackjack. Experiments are conducted with populations employing population learning alone and populations combining population and cultural learning. The article presents results showing the gradual transfer of knowledge from genes to the cultural process, illustrated by the simultaneous decrease in the population's innate fitness and the increase of its acquired fitness measured after learning takes place.     

Multivariate path analysis of cognitive ability measures in reading-disabled and control nuclear families and twins

Matrix notation is used to formulate a multivariate path model of familial resemblance in nuclear families, monozygotic (MZ) twin pairs, and dizygotic (DZ) twin pairs. The model incorporates multivariate genetic and environmental influences, cultural transmission, assortative mating, and environmental influences shared by offspring, and it permits the estimation of genetic and environmental correlations. The model is applied to data from nuclear families, MZ twin pairs, and DZ twin pairs in which at least one child was diagnosed as being reading disabled and to data from control families and twins. Three cognitive ability measures (Reading, Coding Speed, and Spatial Ability) were analyzed simultaneously. Results indicate that genetic influences are moderate, with significant genetic correlations among characters. Cultural transmission is negligible, as are the environmental correlations. Assortative mating is significant only for the Reading measure. There is no evidence for sibling shared environmental influences; however, there are significant twin shared environmental effects for each measure but not between measures.This work was supported by grants from the Spencer Foundation and the NICHD (HD-11681) to J. C. DeFries and by NIMH Postdoctoral Training Grant MH-17104.     

HIV diversity, recombination and disease progression: how does fitness "fit" into the puzzle?

HIV appears to have diverged into several lineages upon multiple zoonotic introductions from the nonhuman primates. The HIV-2 and HIV-1 groups M, N, and O likely represent different cross-species transmission events. The radial evolution of group M in multiple clades or subtypes is likely due to adaptation and expansions in the human hosts. It is not well understood why HIV strains such as HIV-1 subtype C in particular or group M in general have spread disproportionately as compared to other subtypes, groups, or types, which often remained geographically constrained to local epidemics. Host genetic effects, transmission bottlenecks, social/behavioral and environmental limitations, founder effect and other viral factors could have contributed to variable spread through the human population. Even after transmission, viruses evolve at different rates during disease progression. Recent studies have explored phenotypic differences between HIV types, groups, and subtypes in attempts to explain or understand this radial evolution and expansion. This review explores some of the important aspects relating to fitness during disease progression, during global distribution of different HIV subtypes, and related to circulation of recombinant forms in the epidemic.     

Meiotic recombination favors the spreading of deleterious mutations in human populations

Although mutations that are detrimental to the fitness of organisms are expected to be rapidly purged from populations by natural selection, some disease-causing mutations are present at high frequencies in human populations. Several nonexclusive hypotheses have been proposed to account for this apparent paradox (high new mutation rate, genetic drift, overdominance, or recent changes in selective pressure). However, the factors ultimately responsible for the presence at high frequency of disease-causing mutations are still contentious. Here we establish the existence of an additional process that contributes to the spreading of deleterious mutations: GC-biased gene conversion (gBGC), a process associated with recombination that tends to favor the transmission of GC-alleles over AT-alleles. We show that the spectrum of amino acid-altering polymorphisms in human populations exhibits the footprints of gBGC. This pattern cannot be explained in terms of selection and is evident with all nonsynonymous mutations, including those predicted to be detrimental to protein structure and function, and those implicated in human genetic disease. We present simulations to illustrate the conditions under which gBGC can extend the persistence time of deleterious mutations in a finite population. These results indicate that gBGC meiotic drive contributes to the spreading of deleterious mutations in human populations.     

Simple models of assortment through environmental feedback

Social evolution depends critically on assortment, or segregation versus even mixing, between cooperators and noncooperators. Altruistic traits, which reduce the absolute fitness of their bearers, cannot evolve without positive assortment (excess segregation). The question of how positive assortment can arise has been controversial, but most evolutionary biologists believe that common descent is the only effective general mechanism. Here I investigate another recently proposed mechanism for generating nonrandom assortment, termed environmental feedback. This requires only that two forms of a trait affect the quality of the local environment differently in such a way that all individuals are more likely to leave low-quality locales. Experiments with simple computational models confirm that environmental feedback generates significant levels of genetic similarity among non-kin within locales. The mechanism is fairly general, and can under some conditions produce levels of genetic similarity comparable to those resulting from close genealogical relationship. Environmental feedback can also generate the negative assortment necessary for the evolution of spiteful traits. Environmental feedback is expected to create positive frequency-dependent selection, which thus favor any social trait that becomes common in the population. Results from this stylized model suggest that environmental feedback could be important in the evolution of both cooperation and spite, within as well as between species.     

Familial transmission of schizophrenia in Palau: A 20‐year genetic epidemiological study in three generations

Our genetic epidemiological studies of schizophrenia and other psychotic disorders (SCZ) in the isolated population of Palau have been ongoing for 20 years. Results from the first decade showed that Palau has an elevated prevalence of SCZ and that cases cluster in extended multigenerational pedigrees interconnected via complex genetic relationships after centuries of endogamous, but not consanguineous, marriages. The aim of our second decade of research, which extended data collection into a third generation of young, high‐risk (HR) Palauans, was to identify significant predictors of intergenerational transmission of illness. Our findings revealed that degree of familial loading and gender effects on reproductive fitness are important modifiers of risk for transmission of SCZ. Among 45 distinct multiplex families, we identified 10 high‐density (HD) Palauan families, each with 7–29 SCZ cases, which contain half of Palau's 260 SCZ cases and 80% of the 113 SCZ cases with one or more affected first‐degree relatives, indicating that familial loading is a major risk factor for SCZ in Palau. Cases that belong to multiply affected sibships are more common than cases with an affected parent. Furthermore, only 6/38 multiply affected sibships have an affected parent, strong evidence that many unaffected parents are obligate carriers of susceptibility genes. Although reproductive fitness is dramatically reduced in affected males, the 30% minority who do become fathers are twice as likely as affected mothers to transmit SCZ to an offspring. As they evolve, these HD families can help to elucidate the genetic mechanisms that predict intergenerational transmission of SCZ. © 2011 Wiley‐Liss, Inc.     

Population variation of West Nile virus confers a host-specific fitness benefit in mosquitoes

West Nile virus is similar to most other RNA viruses in that it exists in nature as a genetically diverse population. However, the role of this genetic diversity within natural transmission cycles and its importance to virus perpetuation remain poorly understood. Therefore, we determined whether highly genetically diverse populations are more fit compared to less genetically diverse WNV populations. Specifically, we generated three WNV populations that varied in their genetic diversity and evaluated their fitness relative to genetically marked control WNV in vivo in Culex quinquefasciatus mosquitoes and chickens. Our results demonstrate that high genetic diversity leads to fitness gains in vector mosquitoes, but not chickens.     

Analysing the contributions of genes and parent-child interaction to childhood behavioural and emotional problems: a model for the children of twins

BACKGROUND: Despite the demonstrable influence of both genes and the family environment on children's behavioural and emotional development, the mechanisms by which these factors are transmitted from parents to their children are not known. Numerous aspects of the family have long been associated with behavioural and emotional problems in children; it is not clear, however, whether these family variables represent genuine environmental risks or secondary consequences of the underlying genetic liability shared between parents and their children. METHOD: In this study we present a model for analysing the non-genetic contributions of family background to risk for childhood and adolescent depression and conduct disturbance using simulated data on adult MZ and DZ twins, their spouses and children. RESULTS: The twin offspring design provides substantial power to detect remarkably small non-genetic effects on parent-offspring resemblance against the background of genetic transmission. As presented, the model is able to resolve the direction of transmission from both parent to child (passive genotype environment correlation) and child to parent (evocative genotype environment correlation). CONCLUSIONS: Unlike many other genetic studies, a study of twins and their children can sort out which putative family environmental risk factors do actually have a significant environmental impact on the child and which ones only appear to do so because they are associated with genetic mediation.     

Relative fitness of carriers of the mitochondrial DNA mutation 3243A > G

Deleterious point mutations in mitochondrial DNA (mtDNA) have been found in many human populations and always at a low frequency suggesting that they are under strong negative selection. It is assumed that this selection is caused by reduced genetic fitness of mutation carriers, but the fitness of carriers of any mtDNA mutation has not been determined. We estimated the reproductive disadvantage caused by the mitochondrial DNA mutation 3243A > G in a population-based group of female carriers (n = 32). The person-years method, Kaplan-Meier survival analysis and population statistics were used to estimate net reproduction rates of the mutation carriers and the general population. We found that women with 3243A > G reproduced at the same rate as women in the general population, suggesting that on average host-level selection against women harbouring the 3243A > G mutation is not strong.     

Genetic and Cultural Transmission of Smoking Initiation: An Extended Twin Kinship Model

BACKGROUND: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a significant role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent-offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. METHODS: We examined the role of genetic and environmental factors for smoking initiation using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission. A dichotomous lifetime smoking measure was obtained from twins and relatives in the Virginia 30,000 sample. RESULTS: Results demonstrate that both genetic and environmental factors play a significant role in the liability to smoking initiation. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission and resulting genotype-environment covariance. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent-offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (i) age x gene interaction, and (ii) social homogamy. Neither mechanism provided a significantly better explanation of the data, although age regression was significant. CONCLUSIONS: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on smoking initiation.     

Causes of Stability of Aggression from Early Childhood to Adolescence: A Longitudinal Genetic Analysis in Dutch Twins

This study investigated the contribution of genetic and environmental influences on the stability of aggressive behavior from early childhood to adolescence. Two developmental models, the simplex model and the common factor model, were tested to study the underlying processes of stability and change. Measures of aggressive behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing longitudinal study of the Netherlands Twin Registers (NTR) and included data from 6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high stability during childhood. The stability coefficients ranged from 0.41 to 0.77 across varying intervals. Averaged across boys and girls, genetic factors accounted for approximately 65% of the total stability. Longitudinal genetic analysis indicated a simplex model for genetic effects, which suggests a dynamic development process consisting of transmission of existing genetic effects interacting with new genetic influences. This is especially true at age 7, when the influence of new genetic factors was large. Shared environmental factors accounted for approximately 25% of phenotypic stability, and it seemed that a stable set of the same shared environmental factors underlay the development of AGG. Nonshared environmental factors, when important, are age specific. Sex-specific differences for stability were identified. For boys, genetic influences were greater, whereas for girls shared environmental factors were more important. These data support the idea that both genetic and environmental influences play a role in the stability of AGG from age 3 to 12.     

Lousy mums: patterns of vertical transmission of an amphibious louse

In this study, we document patterns of vertical transmission of the amphibious louse Antarctophthirus microchir (Echinophthiriidae) in pups of South American sea lion, Otaria flavescens, from Patagonia. Vertical transmission is fundamental for the long-term stability of A. microchir populations because only pups stay long enough (1 month) on land for the louse to reproduce. A total of 72 pups ≤7 days old from a single rookery were captured and examined for lice. Infection parameters and population structure of A. microchir did not differ among pups collected at the beginning, middle, and end of the reproductive season, suggesting that patterns of early vertical transmission are not affected by the increase of rookery size during this period. Over 60 % of 1-day-old pups were infected with A. microchir, and recruitment increased in pups up to 3 days old and then leveled off. In 1-day-old pups, significantly more adults than nymphs were found, but the pattern was reversed in older pups. The number of first-stage nymphs was significantly smaller than that of second- and third-stage nymphs, as it was the number of males vs. females, particularly in 1-day-old pups. Three non-exclusive hypotheses could account for these patterns, i.e., recruitment merely reflects the population structure of A. microchir is cows; the relative ability of lice to pass from cows onto pups increases in advanced instars; and/or natural selection favors transmission of adults, especially females, because they accrue greater fitness. The importance of latter hypothesis should not be underestimated in a species with a tight reproductive schedule.     

Reproductive Reproductive behaviour and natural selection for the sickle gene in the Baiga Tribe of Central India: The role of social parenting

We have investigated the transmission of the sickle cell gene in relation to tribal structure, and genetic fitness in a primitive Indian tribal population, the Baiga. Factors operating on gene frequency include protection of AS individuals against falciparum malaria, a high frequency of genetic factors capable of moderating the severity of sickle cell anaemia (α-thalassaemia and Xmn I polymorphism in G gamma gene), a high frequency of consanguineous marriage, and reproductive compensation by couples at risk for sickle cell anaemia. The study incidentally made it possible to measure the extent of 'social parenting' in such a tribal society for the first time: deviation from expectation in the distribution of the Hb A and S genes within families suggests that up to 30 % of children may not be offspring of their ostensible parents.     

Genetic polymorphism and fertility parameters in the Aymara of Chile and Bolivia

To determine whether increased fitness in natural populations is associated with heterozygosity, several studies have attempted to correlate heterozygosity at one or a few genetic loci with fitness-related quantitative traits. The results have been equivocal at best. Furthermore, data on fertility-related parameters and the extent of genetic polymorphism at a large number of loci in man are quite scanty. This report examines the association of four fertility-related parameters (number of pregnancies, number of livebirths, number of children surviving at least one year and number of children alive at the time of the survey) with heterozygosity at 17 polymorphic immunological and biochemical systems in the Aymara of Chile and Bolivia. Women 45 years of age and above, on whom complete fertility histories and phenotype data are available, were included in the study (n=190). None of the fertility parameters seem to be correlated with heterozygosity, as measured by the proportion of polymorphic loci. For some individual loci, however, an association between heterozygous state and fertility parameters exists. Even in these cases, heterozygosity did not always confer higher fertility. To see whether these negative results are due to heterogeneity in the data, the total sample was divided according to altitude of residence and ethnicity. The conclusions remained the same, indicating that the lack of association of these fertility parameters with genetic polymorphism is not due to population heterogeneity alone. Reproductive fitness differentials, therefore, were not detectable in the Aymara by heterozygosity determined by the polymorphic genetic systems scored by serological and electrophoretic techniques.