A Concept of Complementarity Between Complexity and Redundancy can Account for Kant's Biological Teleology and Unify Mechanistic and Finalistic Biology.

Over 160 years after Darwin and 70 years after the discovery of DNA, two fundamental questions of biology remain unanswered: What differentiates the living from the nonliving? How can mechanistic and finalistic or holistic biology be unified? Niels Bohr introduced a concept of complementarity in quantum physics and based on the paradox of light as a simultaneous wave and particle, conjectured that a similar concept might exist in biology that would solve the paradox of life originating from the nonliving. Bohr proposed that two mutually exclusive-independent observations may be necessary to explain a phenomenon and provided support to Immanuel Kant's idea that the "purposive" behaviour of organisms could only be explained in teleological terms and that mechanical and teleological approaches were necessary and complementary to explain biology. We present a concept of complementarity whereby biochemical pathways or cellular channels for the flow of information are simultaneously complex and redundant and complexity and redundancy complement each other. The postulates of biological complementarity are that (1) it was an essential condition in the origin of life; (2) it provided physiological flexibility that allowed organisms to mount self-protection response and complexity to evolve in the face of deleterious mutations before the evolution of bi-parental sex; (3) it laid the foundation for the evolution of a choice of response when confronted with threat; and (4) it applies to all levels of biological organizations and, thus, can serve as a basis for the unification of mechanistic and holistic biology. It is proposed that teleology is simultaneously constitutive and heuristic: constitutive because organisms' "purposive" behaviours are adaptive and are grounded in mechanism (complexity and redundancy), and heuristic because with our finite cognition and our goal-oriented (humans alone are aware of "tomorrow") and anthropomorphic pre-disposition, teleology will remain useful as a guide to our making sense of the world, even how to ask a meaningful question.

A Law of Redundancy Compounds the Problem of Cancer and Precision Medicine.

Genetics and molecular biology research have progressed for over a century; however, no laws of biology resembling those of physics have been identified, despite the expectations of some physicists. It may be that it is not the properties of matter alone but evolved properties of matter in combination with atomic physics and chemistry that gave rise to the origin and complexity of life. It is proposed that any law of biology must also be a product of evolution that co-evolved with the origin and progression of life. It was suggested that molecular complexity and redundancy exponentially increase over time and have the following relationship: DNA sequence complexity (Cd) < molecular complexity (Cm) < phenotypic complexity (Cp). This study presents a law of redundancy, which together with the law of complexity, is proposed as an evolutionary law of biology. Molecular complexity and redundancy are inseparable aspects of biochemical pathways, and molecular redundancy provides the first line of defense against environmental challenges, including those of deleterious mutations. Redundancy can create problems for precision medicine because in addition to the issues arising from the involvement of multiple genes, redundancy arising from alternate pathways between genotypes and phenotypes can complicate gene detection for complex diseases and mental disorders. This study uses cancer as an example to show how cellular complexity, molecular redundancy, and hidden variation affect the ability of cancer cells to evolve and evade detection and elimination. Characterization of alternate biochemical pathways or "escape routes" can provide a step in the fight against cancer.

Origin of Sex-Biased Mental Disorders: Do Males and Females Experience Different Selective Regimes?

The origins of sex-biased differences in disease and health are of growing interest to both medical researchers and health professionals. Several major factors have been identified that affect sex differences in incidence of diseases and mental disorders. These are: sex chromosomes, sex hormones and female immunity, sexual selection and antagonistic evolution, and differential susceptibility of sexes to environmental factors. These factors work on different time scales and are not exclusive of each other. Recently, a combined Sexual Selection-Sex Hormones (SS-SH) Theory was presented as an evolutionary mechanism to explain sex-biased differences in diseases and mental disorders (Singh in J Mol Evol 89:195-213, 2021). In that paper disease prevalence trends were investigated, and non-sex-specific diseases were hypothesized to be more common in males than in females in general. They showed signs of exceptions to this trend with inflammatory diseases and stress-related mental disorders that were more common in females. We believe that the SS-SH theory requires the consideration of psycho-social stress (PSS) to explain the predominance of female-biased mental disorders and some other exceptions in their findings. Here we present a theory of sex-differential experience of PSS and provide quantitative support for the combined SS-SH-PSS Theory using age-standardized incidence rates (ASIRs) recording the levels of male- and female-bias in data obtained from different countries. The grand theory provides an evolutionary framework for explaining patterns of sex-biased trends in the prevalence of disease and health. Further exploration of women's vulnerability to social factors may help to facilitate new treatments for female-biased diseases.

Decoding 'Unnecessary Complexity': A Law of Complexity and a Concept of Hidden Variation Behind "Missing Heritability" in Precision Medicine.

The high hopes for the Human Genome Project and personalized medicine were not met because the relationship between genotypes and phenotypes turned out to be more complex than expected. In a previous study we laid the foundation of a theory of complexity and showed that because of the blind nature of evolution, and molecular and historical contingency, cells have accumulated unnecessary complexity, complexity beyond what is necessary and sufficient to describe an organism. Here we provide empirical evidence and show that unnecessary complexity has become integrated into the genome in the form of redundancy and is relevant to molecular evolution of phenotypic complexity. Unnecessary complexity creates uncertainty between molecular and phenotypic complexity, such that phenotypic complexity (CP) is higher than molecular complexity (CM), which is higher than DNA complexity (CD). The qualitative inequality in complexity is based on the following hierarchy: CP > CM > CD. This law-like relationship holds true for all complex traits, including complex diseases. We present a hypothesis of two types of variation, namely open and closed (hidden) systems, show that hidden variation provides a hitherto undiscovered "third source" of phenotypic variation, beside genotype and environment, and argue that "missing heritability" for some complex diseases is likely to be a case of "diluted heritability". There is a need for radically new ways of thinking about the principles of genotype-phenotype relationship. Understanding how cells use hidden, pathway variation to respond to stress can shed light on why two individuals who share the same risk factors may not develop the same disease, or how cancer cells escape death.

Origin of Sex-Biased Mental Disorders: An Evolutionary Perspective.

Sexual dimorphism or sex bias in diseases and mental disorders have two biological causes: sexual selection and sex hormones. We review the role of sexual selection theory and bring together decades of molecular studies on the variation and evolution of sex-biased genes and provide a theoretical basis for the causes of sex bias in disease and health. We present a Sexual Selection-Sex Hormone theory and show that male-driven evolution, including sexual selection, leads to: (1) increased male vulnerability due to negative pleiotropic effects associated with male-driven sexual selection and evolution; (2) increased rates of male-driven mutations and epimutations in response to early fitness gains and at the cost of late fitness; and (3) enhanced female immunity due to antagonistic responses to mutations that are beneficial to males but harmful to females, reducing female vulnerability to diseases and increasing the thresholds for disorders such as autism. Female-driven evolution, such as reproduction-related fluctuation in female sex hormones in association with stress and social condition, has been shown to be associated with increased risk of certain mental disorders such as major depression disorder in women. Bodies have history, cells have memories. An evolutionary framework, such as the Sexual Selection-Sex Hormone theory, provides a historical perspective for understanding how the differences in the sex-biased diseases and mental disorders have evolved over time. It has the potential to direct the development of novel preventive and treatment strategies.

Is menopause still evolving? Evidence from a longitudinal study of multiethnic populations and its relevance to women's health.

BACKGROUND: To reflect on the impact of changing patterns of delayed marriage and reproduction and to seek evidence as to whether menopause is still evolving, characteristics of the menopause transition were investigated within and between ethnic populations in this study. METHODS: A cross-sectional analysis was conducted using data on 747 middle-aged women obtained from the Study of Women's Health Across the Nation (SWAN) from 1996 to 2008. The ethnic groups included: Afro-American, Chinese, Japanese, Caucasian, and Hispanic. Perimenopause age and duration, menopause age, and hormonal indicators of menopause were examined across five ethnicities. RESULTS: We found a similar window of menopause age within populations, but no significant difference in perimenopause and menopause age between populations. The rate of increase of follicle-stimulating hormone and testosterone differed significantly in Hispanics and African-Americans during the menopause transition period. CONCLUSIONS: The broad window of variation in age at menopause within the population and the absence of significant differences between populations, in combination with population variation in menopause symptoms, suggest that menopause is a relatively recently evolved and still evolving trait. Under the mate choice theory of menopause, menopause is the result of the accumulation of infertility mutations in older women due to men's preference for younger mates. We propose a shifting mate choice-shifting menopause model which posits that, as the age of mate choice/marriage shifts to older ages, so will the age at menopause, and that menopause is a transient phase of female fertility; it can de-evolve, be delayed, if not disappear completely. Integrated longitudinal menopausal studies linked with genomics and hormonal studies on diverse ethnic populations can provide valuable information bearing on women's health and personalized medicine.

Rotation of sex combs in Drosophila melanogaster requires precise and coordinated spatio-temporal dynamics from forces generated by epithelial cells.

The morphogenesis of sex combs (SCs), a male trait in many species of fruit flies, is an excellent system in which to study the cell biology, genetics and evolution of a trait. In Drosophila melanogaster, where the incipient SC rotates from horizontal to a vertical position, three signal comb properties have been documented: length, final angle and shape (linearity). During SC rotation, in which many cellular processes are occurring both spatially and temporally, it is difficult to distinguish which processes are crucial for which attributes of the comb. We have used a novel approach combining simulations and experiments to uncover the spatio-temporal dynamics underlying SC rotation. Our results indicate that 1) the final SC shape is primarily controlled by the inhomogeneity of initial cell size in cells close to the immature comb, 2) the final angle is primarily controlled by later cell expansion and 3) a temporal sequence of cell expansion mitigates the malformations generally associated with longer rotated SCs. Overall, our work has linked together the morphological diversity of SCs and the cellular dynamics behind such diversity, thus providing important insights on how evolution may affect SC development via the behaviours of surrounding epithelial cells.

Genomic portrait of population of Jharkhand, India, drawn with 15 autosomal STRs and 17 Y-STRs.

We analysed 15 autosomal STRs in 200 unrelated individuals (102 males and 98 females) and 17 Y-STRs in 102 unrelated males living in Jharkhand, India, to establish parameters of forensic interest. The examined autosomal STRs revealed high combined power of exclusion (CPE) and combined power of discrimination (CPD) as equal to 0.9999 and greater than 0.99999, respectively. The combined probability of match (CPm) and combined paternity index (CPI) for all 15 autosomal STR loci were found to be 5.15 × 10-18 and 6.83 × 105, respectively. A total of 97 unique haplotypes were obtained, of which 93 were observed only once. The haplotype diversity, discrimination capacity and matching probability for 17 Y-STR loci were 0.999, 0.951 and 1.09 × 10-2, respectively. The highest gene diversity values at the single copy locus DYS635 and multi-copy locus DYS385 a/b were 0.785 and 0.823, respectively.

Evolution of Drosophila sex comb length illustrates the inextricable interplay between selection and variation.

In spite of the diversity of possible biological forms observed in nature, a limited range of morphospace is frequently occupied for a given trait. Several mechanisms have been proposed to explain this bias in the distribution of phenotypes including selection, drift, and developmental constraints. Despite extensive work on phenotypic bias, the underlying developmental mechanisms explaining why particular regions of morphological space remain unoccupied are poorly understood. To address this issue, we studied the sex comb, a group of modified bristles used in courtship that shows marked morphological diversity among Drosophila species. In many Drosophila species including Drosophila melanogaster, the sex comb rotates 90° to a vertical position during development. Here we analyze the effect of changing D. melanogaster sex comb length on the process of rotation. We find that artificial selection changes the number of bristles per comb without a proportional change in the space available for rotation. As a result, when increasing sex comb length, rather than displaying a similar straight vertical shape observed in other Drosophila species, long sex combs bend because rotation is blocked by a neighboring row of bristles. Our results show ways in which morphologies that would be favored by natural selection are apparently impossible to achieve developmentally. These findings highlight the potential role of development in modifying selectable variation in the evolution of Drosophila sex comb length.

Science beyond boundary: are premature discoveries things of the past?

Mendel's name more than of any other draws our attention to the personal side in terms of success and failure in science. Mendel lived 19 years after presenting his research findings and died without receiving any recognition for his work. Are premature discoveries things of the past, you may ask? I review the material basis of science in terms of science boundary and field accessibility and analyze the possibility of premature discoveries in different fields of science such as, for example, physics and biology. I conclude that science has reached a stage where progress is being made mostly by pushing the boundary of the known from inside than by leaping across boundaries. As more researchers become engaged in science, and as more publications become open access, on-line, and interactive, the probability of an important discovery remaining buried and going unrecognized would become exceedingly small. Of course, as examples from physics show, a new theory or an important idea can always lie low, unrecognized until it becomes re-discovered and popularized by other researchers. Thus, premature discoveries will become less likely but not forbidden.

Limits of imagination: the 150th Anniversary of Mendel's Laws, and why Mendel failed to see the importance of his discovery for Darwin's theory of evolution.

Mendel is credited for discovering Laws of Heredity, but his work has come under criticism on three grounds: for possible falsification of data to fit his expectations, for getting undue credit for the laws of heredity without having ideas of segregation and independent assortment, and for being interested in the development of hybrids rather than in the laws of heredity. I present a brief review of these criticisms and conclude that Mendel deserved to be called the father of genetics even if he may not, and most likely did not, have clear ideas of segregation and particulate determiners as we know them now. I argue that neither Mendel understood the evolutionary significance of his findings for the problem of genetic variation, nor would Darwin have understood their significance had he read Mendel's paper. I argue that the limits to imagination, in both cases, came from their mental framework being shaped by existing paradigms-blending inheritance in the case of Darwin, hybrid development in the case of Mendel. Like Einstein, Darwin's natural selection was deterministic; like Niels Bohr, Mendel's Laws were probabilistic-based on random segregation of trait-determining "factors". Unlike Einstein who understood quantum mechanics, Darwin would have been at a loss with Mendel's paper with no guide to turn to. Geniuses in their imaginations are like heat-seeking missiles locked-in with their targets of deep interests and they generally see things in one dimension only. Imagination has limits; unaided imagination is like a bird without wings--it goes nowhere.

Darwin's legacy II: why biology is not physics, or why it has taken a century to see the dependence of genes on the environment.

Genes and environment make the organism. Darwin stood firm in his denial of any direct role of environment in the modification of heredity. His theory of evolution heralded two debates: one about the importance and adequacy of natural selection as the main mechanism of evolution, and the other about the role of genes versus environment in the modification of phenotype and evolution. Here, I provide an overview of the second debate and show that the reasons for the gene versus environment battle were twofold: first, there was confusion about the role of environment in modifying the inheritance of a trait versus the evolution of that trait, and second, there was misunderstanding about the meaning of environment and its interaction with genes in the production of phenotypes. It took nearly a century to see that environment does not directly affect the inheritance of a phenotype (i.e., its heredity), but it is nevertheless the primary mover of phenotypic evolution. Effects of genes and environment are not separate but interdependent. One cannot separate the effect of genes from that of environment, or nature from nurture. To answer the question posed in the title, it is partly because the 20th century has been a century of unending progress in genetics. But also because unlike physics, biology is not colorblind; progress in biology has often been delayed beyond the Kuhnian paradigm change due to built-in interest in negating the influence of environment. Those who are against evolution, of course, cannot be expected to understand the role of environment in evolution. Those for it, many biologists included, believing in the supremacy of genes empowers them by giving adaptation a solely gene-directed (self-driven) "teleological" interpretation.

Maternal effect and speciation: maternal effect contributes to the evolution of hybrid inviability between Drosophila simulans and Drosophila mauritiana.

Haldane's rule has been the basis of speciation research during the last 30 years. Most studies have focused on the nature of incompatibilities in the hybrid male, but not much attention has been given to the genetic basis of fertility and inviability in hybrid females. Hybridizations between Drosophila simulans and Drosophila mauritiana produce fertile females and sterile males. Here, we re-examined the level of fertility in reciprocal F1 females of these two species and looked for the presence of maternal effects. Our results show that the reciprocal F1 females of D. simulans and D. mauritiana hybridizations are fully fertile and in fact show a significant level of heterosis in the rate of oviposition but display reduced egg hatching in one direction. Reduced egg hatching was observed in the progenies of F1 hybrid females with D. mauritiana as mother, the same cross that showed a stronger negative effect on F1 male fertility. A review of the literature on the hybridizations in Lepidoptera also showed a maternal effect on inviability when reciprocal crosses produced asymmetric results. Our findings point to the importance of maternal effects in the evolution of embryo inviability and thus enhancing the process of speciation through the evolution of hybrid inviability.

Dose-dependent effects of Asparagus adscendens root (AARR) extract on the anabolic, reproductive, and sexual behavioral activity in rats.

CONTEXT: Asparagus adscendens Roxb (Liliaceae) has a promising role in modulation of various disorders such as leucorrhea, diarrhea, dysentery, diabetes, senile pruritus, asthma, fatigue antifilarial, antifungal, spermatorrhea, and sexual debility/seminal weakness. OBJECTIVE: To investigate dose-dependent effects of Asparagus adscendens root (AARR) extract on anabolic, reproductive, and sexual behavioral activities with a view to emphasize the pharmacological basis. MATERIALS AND METHODS: Rats were divided into five groups: Group I (control), Groups II-IV (AARR treated, 100, 200, and 300 mg/kg body weight, respectively, orally for 30 d) and Group V (standard control treated with sildenafil citrate, 5 mg/kg body weight). On day 31, copulatory and potency tests were carried out and an autopsy was done to study the reproductive function, namely, organ weights, spermatogenesis, daily sperm production rate (DSP), and epididymal sperm counts (ESC). RESULTS: AARR extract (200 and 300 mg/kg doses) caused a significant increase in body (p < 0.02 and p < 0.001) and testes (p < 0.01 and p < 0.001, control versus treated) weights. Reproductive activity showed significant a increase in testicular tubular diameter (p < 0.005-0.001), the number of round/elongated spermatids (p < 0.02-0.001), DSP, and ESC (p < 0.05-0.001). The sexual behavioral parameters including mounting/intromission frequency (13.0 ± 0.32/11.8 ± 0.37 and 18.2 ± 2.12/14.8 ± 1.15 versus 11.2 ± 0.66/8.2 ± 1.16), ejaculation latency (187.4 ± 1.91 and 191.4 ± 1.72 versus 180.0 ± 3.47), and penile erections (13.5 ± 0.3 and 14.5 ± 0.5 versus 8.5 ± 0.2) showed a significant increase at 200 and 300 mg/kg doses (ED50 300 mg/kg), but less than a standard control. In contrast, 100 mg/kg dose caused an increase (p < 0.005) in mounting latency only. CONCLUSION: These results indicate increased anabolic, reproductive, and sexual activities by AARR treatment. Thus, the data provide scientific rationale for its traditional use as an aphrodisiac or for sexual disorders.

Mate choice and the origin of menopause.

Human menopause is an unsolved evolutionary puzzle, and relationships among the factors that produced it remain understood poorly. Classic theory, involving a one-sex (female) model of human demography, suggests that genes imparting deleterious effects on post-reproductive survival will accumulate. Thus, a 'death barrier' should emerge beyond the maximum age for female reproduction. Under this scenario, few women would experience menopause (decreased fertility with continued survival) because few would survive much longer than they reproduced. However, no death barrier is observed in human populations. Subsequent theoretical research has shown that two-sex models, including male fertility at older ages, avoid the death barrier. Here we use a stochastic, two-sex computational model implemented by computer simulation to show how male mating preference for younger females could lead to the accumulation of mutations deleterious to female fertility and thus produce a menopausal period. Our model requires neither the initial assumption of a decline in older female fertility nor the effects of inclusive fitness through which older, non-reproducing women assist in the reproductive efforts of younger women. Our model helps to explain why such effects, observed in many societies, may be insufficient factors in elucidating the origin of menopause.

Condition dependence and the nature of genetic variation for male sex comb bristle number in Drosophila melanogaster.

Genetic architecture of variation underlying male sex comb bristle number, a rapidly evolving secondary sexual character of Drosophila, was examined. First, in order to test for condition dependence, diet was manipulated in a set of ten Drosophila melanogaster full-sib families. We confirmed heightened condition dependent expression of sex comb bristle number and its female homologue (distal transverse row bristles) as compared to non-sex sternopleural bristles. Significant genotype by environment effects were detected for the sex traits indicating a genetic basis for condition dependence. Next we measured sex comb bristle number and sternopleural bristle number, as well as residual mass, a commonly used condition index, in a set of thirty half-sib families. Sire effect was not significant for sex comb and sternopleural bristle number, and we detected a strong dominance and/or maternal effect or X chromosome effect for both traits. A strong sire effect was detected for condition and its heritability was the highest as compared to sex comb and sternopleural bristles. We discuss our results in light of the rapid response to divergent artificial selection for sex comb bristle number reported previously. The nature of genetic variation for male sex traits continues to be an important unresolved issue in evolutionary biology.

Darwin's legacy: why biology is not physics, or why evolution has not become a common sense.

Cosmology and evolution together have enabled us to look deep into the past and comprehend evolution-from the big bang to the cosmos, from molecules to humans. Here, I compare the nature of theories in biology and physics and ask why physical theories get accepted by the public without necessarily comprehending them but biological theories do not. Darwin's theory of natural selection, utterly simple in its premises but profound in its consequences, is not accepted widely. Organized religions, and creationists in particularly, have been the major critic of evolution, but not all opposition to evolution comes from organized religions. A great many people, between evolutionary biologists on one hand and creationists on the other, many academics included, who may not be logically opposed to evolution nevertheless do not accept it. This is because the process of and the evidence for evolution are invisible to a nonspecialist, or the theory may look too simple to explain complex traits to some, or because people compare evolution against God and find evolutionary explanations threatening to their beliefs. Considering how evolution affects our lives, including health and the environment to give just two examples, a basic course in evolution should become a required component of all our college and university educational systems.

Molecular evidence for increased regulatory conservation during metamorphosis, and against deleterious cascading effects of hybrid breakdown in Drosophila.

BACKGROUND: Speculation regarding the importance of changes in gene regulation in determining major phylogenetic patterns continues to accrue, despite a lack of broad-scale comparative studies examining how patterns of gene expression vary during development. Comparative transcriptional profiling of adult interspecific hybrids and their parental species has uncovered widespread divergence of the mechanisms controlling gene regulation, revealing incompatibilities that are masked in comparisons between the pure species. However, this has prompted the suggestion that misexpression in adult hybrids results from the downstream cascading effects of a subset of genes improperly regulated in early development. RESULTS: We sought to determine how gene expression diverges over development, as well as test the cascade hypothesis, by profiling expression in males of Drosophila melanogaster, D. sechellia, and D. simulans, as well as the D. simulans (female) x D. sechellia (male) male F1 hybrids, at four different developmental time points (3rd instar larval, early pupal, late pupal, and newly-emerged adult). Contrary to the cascade model of misexpression, we find that there is considerable stage-specific autonomy of regulatory breakdown in hybrids, with the larval and adult stages showing significantly more hybrid misexpression as compared to the pupal stage. However, comparisons between pure species indicate that genes expressed during earlier stages of development tend to be more conserved in terms of their level of expression than those expressed during later stages, suggesting that while Von Baer's famous law applies at both the level of nucleotide sequence and expression, it may not apply necessarily to the underlying overall regulatory network, which appears to diverge over the course of ontogeny and which can only be ascertained by combining divergent genomes in species hybrids. CONCLUSION: Our results suggest that complex integration of regulatory circuits during morphogenesis may lead to it being more refractory to divergence of underlying gene regulatory mechanisms--more than that suggested by the conservation of gene expression levels between species during earlier stages. This provides support for a 'developmental hourglass' model of divergence of gene expression in Drosophila resulting in a highly conserved pupal stage.

Male sex drive and the maintenance of sex: evidence from Drosophila.

The resolution of the paradoxes surrounding the evolutionary origins and maintenance of sexual reproduction has been a major focus in biology. The operation of sexual selection-which is very common among multicellular organisms-has been proposed as an important factor in the maintenance of sex, though in order for this hypothesis to hold, the strength of sexual selection must be stronger in males than in females. Sexual selection poses its own series of evolutionary questions, including how genetic variability is maintained in the face of sustained directional selection (known as the "paradox of the lek"). In this short review, we present evidence obtained from recent comparative genomics projects arguing that 1) the genomic consequences of sexual selection clearly show that its effect is stronger in males and 2) this sustained selection over evolutionary timescales also has an effect of capturing de novo genes and expression patterns influencing male fitness, thus providing a mechanism via which new genetic variation can be input into to male traits. Furthermore, we argue that this latter process of genomic "masculinization" has an additional effect of making males difficult to purge from populations, as evidence from Drosophila indicates that, for example, many male sexually selected seminal fluid factors are required to ensure maximally efficient reproduction. Newly arising parthenogenic mutations would suffer an immediate reproductive rate disadvantage were these proteins lost. We show that recent studies confirm that genomic masculinization, as a result of "male sex drive," has important consequences for the evolution of sexually dimorphic species.

Ontogeny and phylogeny: molecular signatures of selection, constraint, and temporal pleiotropy in the development of Drosophila.

BACKGROUND: Karl Ernst Von Baer noted that species tend to show greater morphological divergence in later stages of development when compared to earlier stages. Darwin originally interpreted these observations via a selectionist framework, suggesting that divergence should be greatest during ontogenic stages in which organisms experienced varying 'conditions of existence' and opportunity for differential selection. Modern hypotheses have focused on the notion that genes and structures involved in early development will be under stronger purifying selection due to the deleterious pleiotropic effects of mutations propagating over the course of ontogeny, also known as the developmental constraint hypothesis. RESULTS: Using developmental stage-specific expressed sequence tag (EST) libraries, we tested the 2 hypotheses by comparing the rates of evolution of 7,180 genes obtained from 6 species of the Drosophila melanogaster group with respect to ontogeny, and sex and reproduction-related functions in gonadal tissues. Supporting morphological observations, we found evidence of a pattern of increasing mean evolutionary rate in genes that are expressed in subsequent stages of development. Furthermore, supporting expectations that early expressed genes are constrained in divergence, we found that embryo stage genes are involved in a higher mean number of interactions as compared to later stages. We noted that the accelerated divergence of genes in the adult stage is explained by those expressed specifically in the male gonads, whose divergence is driven by positive selection. In addition, accelerated gonadal gene divergence occurs only in the adult stage, suggesting that the effects of selection are observed primarily at the stages during which they are expected occur. Finally, we also found a significant correlation between temporal specificity of gene expression and evolutionary rate, supporting expectations that genes with ubiquitous expression are under stronger constraint. CONCLUSION: Taken together, these results support both the developmental constraint hypothesis limiting the divergence of early expressed developmentally important genes, leading to a gradient of divergence rates over ontogeny (embryonic < larval/pupal < adult), as well as Darwin's 'selection opportunity' hypothesis leading to increased divergence in adults, particularly in the case of reproductive tissues. We suggest that a constraint early/opportunity late model best explains divergence over ontogeny.