Quantitative Genetics,Pleiotropy, and Morphological Integration in the Dentition of <Emphasis Type="Italic">Papio hamadryas</Emphasis>

Variation in the mammalian dentition is highly informative of adaptations and evolutionary relationships, and consequently has been the focus of considerable research. Much of the current research exploring the genetic underpinnings of dental variation can trace its roots to Olson and Miller’s 1958 book Morphological Integration. These authors explored patterns of correlation in the post-canine dentitions of the owl monkey and Hyopsodus, an extinct condylarth from the Eocene. Their results were difficult to interpret, as was even noted by the authors, due to a lack of genetic information through which to view the patterns of correlation. Following in the spirit of Olson and Miller’s research, we present a quantitative genetic analysis of dental variation in a pedigreed population of baboons. We identify patterns of genetic correlations that provide insight to the genetic architecture of the baboon dentition. This genetic architecture indicates the presence of at least three modules: an incisor module that is genetically independent of the post-canine dentition, and a premolar module that demonstrates incomplete pleiotropy with the molar module. We then compare this matrix of genetic correlations to matrices of phenotypic correlations between the same measurements made on museum specimens of another baboon subspecies and the Southeast Asian colobine Presbytis. We observe moderate significant correlations between the matrices from these three primate taxa. From these observations we infer similarity in modularity and hypothesize a common pattern of genetic integration across the dental arcade in the Cercopithecoidea.     

A MODULAR FRAMEWORK CHARACTERIZES MICRO‐ AND MACROEVOLUTION OF OLD WORLD MONKEY DENTITIONS

The study of modularity can provide a foundation for integrating development into studies of phenotypic evolution. The dentition is an ideal phenotype for this as it is developmentally relatively simple, adaptively highly significant, and evolutionarily tractable through the fossil record. Here, we use phenotypic variation in the dentition to test a hypothesis about genetic modularity. Quantitative genetic analysis of size variation in the baboon dentition indicates a genetic modular framework corresponding to tooth type categories. We analyzed covariation within the dentitions of six species of Old World monkeys (OWMs) to assess the macroevolutionary extent of this framework: first by estimating variance–covariance matrices of linear tooth size, and second by performing a geometric morphometric (GM) analysis of tooth row shape. For both size and shape, we observe across OWMs a framework of anterior and postcanine modules, as well as submodularity between the molars and premolars. Our results of modularity by tooth type suggest that adult variation in the OWM dentition is influenced by early developmental processes such as odontogenesis and jaw patterning. This study presents a comparison of genotypic modules to phenotypic modules, which can be used to better understand their action across evolutionary time scales.     

Evidence of strong stabilizing effects on the evolution of boreoeutherian (Mammalia) dental proportions

The dentition is an extremely important organ in mammals with variation in timing and sequence of eruption, crown morphology, and tooth size enabling a range of behavioral, dietary, and functional adaptations across the class. Within this suite of variable mammalian dental phenotypes, relative sizes of teeth reflect variation in the underlying genetic and developmental mechanisms. Two ratios of postcanine tooth lengths capture the relative size of premolars to molars (premolar–molar module, PMM), and among the three molars (molar module component, MMC), and are known to be heritable, independent of body size, and to vary significantly across primates. Here, we explore how these dental traits vary across mammals more broadly, focusing on terrestrial taxa in the clade of Boreoeutheria (Euarchontoglires and Laurasiatheria). We measured the postcanine teeth of N = 1,523 boreoeutherian mammals spanning six orders, 14 families, 36 genera, and 49 species to test hypotheses about associations between dental proportions and phylogenetic relatedness, diet, and life history in mammals. Boreoeutherian postcanine dental proportions sampled in this study carry conserved phylogenetic signal and are not associated with variation in diet. The incorporation of paleontological data provides further evidence that dental proportions may be slower to change than is dietary specialization. These results have implications for our understanding of dental variation and dietary adaptation in mammals.     

Statistical genetics of molar cusp patterning in pedigreed baboons: implications for primate dental development and evolution

Gene expression and knock-out studies provide considerable information about the genetic mechanisms required for tooth organogenesis. Quantitative genetic studies of normal phenotypic variation are complementary to these developmental studies and may help elucidate the genes and mechanisms that contribute to the normal population-level phenotypic variation upon which selection acts. Here we present the first quantitative genetic analysis of molar cusp positioning in mammals. We analyzed quantitative measures of molar cusp position in a captive pedigreed baboon breeding colony housed at the Southwest National Primate Research Center in San Antonio, Texas. Our results reveal complete pleiotropy between antimeric pairs of traits--i.e., they are influenced by the same gene or suite of genes. Mandibular morphological homologues in the molar series also exhibit complete pleiotropy. In contrast, morphological homologues in maxillary molar series appear to be influenced by partial, incomplete pleiotropic effects. Variation in the mandibular mesial and distal molar loph orientation on the same molar crown is estimated to be genetically independent, whereas the maxillary molar mesial and distal loph orientation is estimated to have partially overlapping genetic affects. The differences between the maxillary and mandibular molar patterning, and the degree of genetic independence found between lophs on the same molar crown, may be indicative of previously unrecognized levels of modularity in the primate dentition.     

Cortical Folding of the Primate Brain: An Interdisciplinary Examination of the Genetic Architecture,Modularity, and Evolvability of a Significant Neurological Trait in Pedigreed Baboons (Genus Papio)

Folding of the primate brain cortex allows for improved neural processing power by increasing cortical surface area for the allocation of neurons. The arrangement of folds (sulci) and ridges (gyri) across the cerebral cortex is thought to reflect the underlying neural network. Gyrification, an adaptive trait with a unique evolutionary history, is affected by genetic factors different from those affecting brain volume. Using a large pedigreed population of ∼1000 Papio baboons, we address critical questions about the genetic architecture of primate brain folding, the interplay between genetics, brain anatomy, development, patterns of cortical–cortical connectivity, and gyrification’s potential for future evolution. Through Mantel testing and cluster analyses, we find that the baboon cortex is quite evolvable, with high integration between the genotype and phenotype. We further find significantly similar partitioning of variation between cortical development, anatomy, and connectivity, supporting the predictions of tension-based models for sulcal development. We identify a significant, moderate degree of genetic control over variation in sulcal length, with gyrus-shape features being more susceptible to environmental effects. Finally, through QTL mapping, we identify novel chromosomal regions affecting variation in brain folding. The most significant QTL contain compelling candidate genes, including gene clusters associated with Williams and Down syndromes. The QTL distribution suggests a complex genetic architecture for gyrification with both polygeny and pleiotropy. Our results provide a solid preliminary characterization of the genetic basis of primate brain folding, a unique and biomedically relevant phenotype with significant implications in primate brain evolution.     

A genomewide linkage scan for quantitative trait loci influencing the craniofacial complex in baboons (Papio hamadryas spp.)

Numerous studies have detected significant contributions of genes to variation in development, size, and shape of craniofacial traits in a number of vertebrate taxa. This study examines 43 quantitative traits derived from lateral cephalographs of 830 baboons (Papio hamadryas) from the pedigreed population housed at the Southwest National Primate Research Center. Quantitative genetic analyses were conducted using the SOLAR analytic platform, a maximum-likelihood variance components method that incorporates all familial information for parameter estimation. Heritability estimates were significant and of moderate to high magnitude for all craniofacial traits. Additionally, 14 significant quantitative trait loci (QTL) were identified for 12 traits from the three developmental components (basicranium, splanchnocranium, and neurocranium) of the craniofacial complex. These QTL were found on baboon chromosomes (and human orthologs) PHA1 (HSA1), PHA 2 (HSA3), PHA4 (HSA6), PHA11 (HSA12), PHA13 (HSA2), PHA16 (HSA17), and PHA17 (HSA13) (PHA, P. hamadryas; HSA, Homo sapiens). This study of the genetic architecture of the craniofacial complex in baboons provides the groundwork needed to establish the baboon as an animal model for the study of genetic and nongenetic influences on craniofacial variation.     

Quantitative trait loci mapping of floral and leaf morphology traits in Arabidopsis thaliana: evidence for modular genetic architecture

Summary Morphological variation within organisms is integrated and often modular in nature. That is to say, the size and shape of traits tend to vary in a coordinated and structured manner across sets of organs or parts of an organism. The genetic basis of this morphological integration is largely unknown. Here, we report on quantitative trait loci (QTL) analysis of leaf and floral organ size in Arabidopsis thaliana. We evaluate patterns of genetic correlations among traits and perform whole-genome scans using QTL mapping methods. We detected significant genetic variation for the size and shape of each floral and leaf trait in our study. Moreover, we found large positive genetic correlations among sets of either flower or leaf traits, but low and generally nonsignificant genetic correlations between flower and leaf traits. These results support the hypothesis of independent floral and vegetative modules. We consider co-localization of QTL for different traits as support for a pleiotropic basis of morphological integration and modularity. A total of eight QTL affecting flower and three QTL affecting leaf traits were identified. Most QTL affected either floral or leaf traits, providing a general explanation for high correlations within and low correlations between modules. Only two genomic locations affected both flower and leaf growth. These results are discussed in the context of the evolution of modules, pleiotropy, and the putative homologous relationship between leaves and flowers.     

Lingual incisor traits in modern hominoids and an assessment of their utility for fossil hominoid taxonomy

The morphology of the anterior dentition has received scant attention for purposes of taxonomic discrimination. Recently, however, lingual incisor morphology was used in differentiating several Miocene ape species and genera. This paper assesses the utility of this morphology for taxonomic discrimination by examining the nature and patterns of variation in lingual incisor morphology in extensive samples of modern chimpanzees, gorillas, orangutans, and gibbons. This paper documents discrete morphological traits on the lingual side of incisors. Trait frequencies are used in univariate and multivariate analyses to examine the apportionment of variation in species, subspecies, and populations. A correlation between lingual incisor traits, tooth dimensions, and sex attempts to determine if such factors affect the manifestation of traits. Finally, the findings are applied to understanding patterns of variation in the Miocene hominids. The study demonstrates that: 1) lingual incisor morphology differs substantially between the hylobatids and great apes; 2) variation in incisor traits is high within species, and most of it is found within local populations; and 3) incisor traits do not correlate significantly with incisor dimensions or sex. Species and to some extent subspecies of extant hominoids can be differentiated statistically using lingual incisor traits, but the frequency of traits such as continuous or discontinuous cingulum, or the presence or absence of pillars, differentiates them. Given this pattern of variation, I argue that it is necessary to assume and document similar patterns of variation in Miocene apes before incisor morphology is used for differentiating taxa.     

Evolution of genetically correlated traits: tooth size and body size in baboons

Within a population, only phenotypic variation that is influenced by genes will respond to selection. Genes with pleiotropic effects are known to influence numerous traits, complicating our understanding of their evolution through time. Here we use quantitative genetic analyses to identify and estimate the shared genetic effects between molar size and trunk length in a pedigreed, breeding population of baboons housed at the Southwest National Primate Research Center. While crown area has a genetic correlation with trunk length, specific linear measurements yield different results. We find that variation in molar buccolingual width and trunk length is influenced by overlapping additive genetic effects. In contrast, mesiodistal molar length appears to be genetically independent of body size. This is the first study to demonstrate a significant genetic correlation between tooth size and body size in primates. The evolutionary implications are discussed.     

Genetic structure of a tribal population, the Yanomama Indians. XIII. Dental microdifferentiation.

Data are presented on the frequency of the following eight dental traits in 635 Yanomama and 65 Makiritare Indians: upper central incisor rotation or winging, shoveling of maxillary incisors, maxillary molar hypocone reduction, Carabelli's trait, mandibular molar cusp number, mandibular molar cusp pattern rotation of second lower premolar, and pattern of second lower premolar cusps. Yanomama dentition is unusual in the high frequency of six cusps on the mandibular molars. There is marked dental microdifferentiation between villages; significant agreement was observed between a matrix of pairwise "dental distances" based on six morphological traits and corresponding matrices based on 11 genetic systems and on geographic location.     

Pleiotropic effects on mandibular morphology II: differential epistasis and genetic variation in morphological integration

The evolution of morphological modularity through the sequestration of pleiotropy to sets of functionally and developmentally related traits requires genetic variation in the relationships between traits. Genetic variation in relationships between traits can result from differential epistasis, where epistatic relationships for pairs of loci are different for different traits. This study maps relationship quantitative trait loci (QTLs), specifically QTLs that affect the relationship between individual mandibular traits and mandible length, across the genome in an F2 intercross of the LG/J and SM/J inbred mouse strains (N = 1045). We discovered 23 relationship QTLs scattered throughout the genome. All mandibular traits were involved in one or more relationship QTL. When multiple traits were affected at a relationship QTL, the traits tended to come from a developmentally restricted region of the mandible, either the muscular processes or the alveolus. About one-third of the relationship QTLs correspond to previously located trait QTLs affecting the same traits. These results comprise examples of genetic variation necessary for an evolutionary response to selection on the range of pleiotropic effects.     

Genetic variation in pleiotropy: differential epistasis as a source of variation in the allometric relationship between long bone lengths and body weight

Pleiotropy is an aspect of genetic architecture underlying the phenotypic covariance structure. The presence of genetic variation in pleiotropy is necessary for natural selection to shape patterns of covariation between traits. We examined the contribution of differential epistasis to variation in the intertrait relationship and the nature of this variation. Genetic variation in pleiotropy was revealed by mapping quantitative trait loci (QTLs) affecting the allometry of mouse limb and tail length relative to body weight in the mouse-inbred strain LG/J by SM/J intercross. These relationship QTLs (rQTLs) modify relationships between the traits affected by a common pleiotropic locus. We detected 11 rQTLs, mostly affecting allometry of multiple bones. We further identified epistatic interactions responsible for the observed allometric variation. Forty loci that interact epistatically with the detected rQTLs were identified. We demonstrate how these epistatic interactions differentially affect the body size variance and the covariance of traits with body size. We conclude that epistasis, by differentially affecting both the canalization and mean values of the traits of a pleiotropic domain, causes variation in the covariance structure. Variation in pleiotropy maintains evolvability of the genetic architecture, in particular the evolvability of its modular organization.     

The quantitative-genetic and QTL architecture of trait integration and modularity in Brassica rapa across simulated seasonal settings

Within organisms, groups of traits with different functions are frequently modular, such that variation among modules is independent and variation within modules is tightly integrated, or correlated. Here, we investigated patterns of trait integration and modularity in Brassica rapa in response to three simulated seasonal temperature/photoperiod conditions. The goals of this research were to use trait correlations to understand patterns of trait integration and modularity within and among floral, vegetative and phenological traits of B. rapa in each of three treatments, to examine the QTL architecture underlying patterns of trait integration and modularity, and to quantify how variation in temperature and photoperiod affects the correlation structure and QTL architecture of traits. All floral organs of B. rapa were strongly correlated, and contrary to expectations, floral and vegetative traits were also correlated. Extensive QTL co-localization suggests that covariation of these traits is likely due to pleiotropy, although physically linked loci that independently affect individual traits cannot be ruled out. Across treatments, the structure of genotypic and QTL correlations was generally conserved. Any observed variation in genetic architecture arose from genotype × environment interactions (GEIs) and attendant QTL × E in response to temperature but not photoperiod.     

Genetics and the evolution of primate enamel thickness: a baboon model

The thickness of mammalian tooth enamel plays a prominent role in paleontology because it correlates with diet, and thicker enamel protects against tooth breakage and wear. Hominid evolutionary studies have stressed the importance of this character for over 30 years, from the identification of "Ramapithecus" as an early Miocene hominid, to the recent discovery that the earliest hominids display molar enamel intermediate in thickness between extant chimpanzees and Australopithecus. Enamel thickness remains largely unexplored for nonhominoid primate fossils, though there is significant variation across modern species. Despite the importance of enamel thickness variation to primate evolution, the mechanisms underlying variation in this trait have not yet been elucidated. We report here on the first quantitative genetic analysis of primate enamel thickness, an analysis based on 506 pedigreed baboons from a captive breeding colony. Computed tomography analysis of 44 Papio mandibular molars shows a zone of sufficiently uniform enamel thickness on the lateral surface of the protoconid. With this knowledge, we developed a caliper metric measurement protocol for use on baboon molars worn to within this zone, enabling the collection of a data set large enough for genetic analyses. Quantitative genetic analyses show that a significant portion of the phenotypic variance in enamel thickness is due to the additive effects of genes and is independent of sex and tooth size. Our models predict that enamel thickness could rapidly track dietary adaptive shifts through geological time, thus increasing the potential for homoplasy in this character. These results have implications for analyses of hominoid enamel thickness variation, and provide a foundation from which to explore the evolution of this phenotype in the papionin fossil record.     

Genotype-Phenotype Maps Maximizing Evolvability: Modularity Revisited

The mechanisms translating genetic to phenotypic variation determine the distribution of heritable phenotypic variance available to selection. Pleiotropy is an aspect of this structure that limits independent variation of characters. Modularization of pleiotropy has been suggested to promote evolvability by restricting genetic covariance among unrelated characters and reducing constraints due to correlated response. However, modularity may also reduce total genetic variation of characters. We study the properties of genotype-phenotype maps that maximize average conditional evolvability, measured as the amount of unconstrained genetic variation in random directions of phenotypic space. In general, maximal evolvability occurs by maximizing genetic variance and minimizing genetic covariance. This does not necessarily require modularity, only patterns of pleiotropy that cancel on average. The detailed structure of the most evolvable genotype-phenotype maps depends on the distribution of molecular variance. When molecular variance is determined by mutation-selection equilibrium either highly pleiotropic or highly modular genotype-phenotype maps can be optimal, depending on the mutation rate and the relative strengths of stabilizing selection on the characters.     

Quantitative genetic analyses of complex behaviours in Drosophila

Behaviours are exceptionally complex quantitative traits. Sensitivity to environmental variation and genetic background, the presence of sexual dimorphism, and the widespread functional pleiotropy that is inherent in behavioural phenotypes pose daunting challenges for unravelling their underlying genetics. Drosophila melanogaster provides an attractive system for elucidating the unifying principles of the genetic architectures that drive behaviours, as genetically identical individuals can be reared rapidly in controlled environments and extensive publicly accessible genetic resources are available. Recent advances in quantitative genetic and functional genomic approaches now enable the extensive characterization of complex genetic networks that mediate behaviours in this important model organism.     

Cranial modularity shifts during mammalian evolution

The mammalian skull has been studied as several separate functional components for decades, but the study of modularity is a more recent, integrative approach toward quantitative examination of independent subsets of highly correlated traits, or modules. Although most studies of modularity focus on developmental and genetic systems, phenotypic modules have been noted in many diverse morphological structures. However, few studies have provided empirical data for comparing modules across higher taxonomic levels, limiting the ability to assess the broader evolutionary significance of modularity. This study uses 18-32 three-dimensional cranial landmarks to analyze phenotypic modularity in 106 mammalian species and demonstrates that cranial modularity is generally conserved in the evolution of therian mammals (marsupials and placentals) but differs between therians and monotremes, the two extant subclasses of Mammalia. Within therians, cluster analyses identify six distinct modules, but only three modules display significant integration in all species. Monotremes display only two highly integrated modules. Specific hypotheses of functional and developmental influences on cranial bones were tested. Theoretical correlation matrices for bones were constructed on the basis of shared function, tissue origin, or mode of ossification, and all three of these models are significantly correlated with observed correlation matrices for the mammalian cranium.     

Cranial ontogeny of Papio baboons (Papio hamadryas)

Cranial form in subspecies of Papio baboons (Papio hamadryas) varies in relation to size, geography, and sex. However, knowledge about this variation is based mainly on adults, precluding direct assessments of the evolutionary factors that are ultimately responsible for adult shape variation. Consequently, this study tests hypotheses about the development of size and shape differences among subspecies of Papio baboons, anticipating limited evolutionary divergences in the ontogenetic pathways leading to adult endpoints. Geometric morphometric and bivariate allometric analyses are used to explore developmental size and shape variation. Allometric scaling in adult Papio baboons occurs because both sexes and all subspecies follow similar developmental pathways to a variety of adult forms. However, complex allometry contributes to form differences, producing potentially important shape differences that emerge during development. Modest shape differences that are statistically independent of size distinguish chacma baboons (P. h. ursinus) from other forms. A small-headed subspecies, the Kinda baboon (P. h. kindae), also presents a distinctive ontogeny, and may provide insights into the evolution of size change in this species. Variation among subspecies that is statistically independent of size involves the rostrum, zygomatic breadths, and cranial flexion. These features may be related to diet, but the precise biomechanical correlates of baboon form variation remain unclear.     

SIZE VARIATION,GROWTH STRATEGIES,AND THE EVOLUTION OF MODULARITY IN THE MAMMALIAN SKULL

Allometry is a major determinant of within‐population patterns of association among traits and, therefore, a major component of morphological integration studies. Even so, the influence of size variation over evolutionary change has been largely unappreciated. Here, we explore the interplay between allometric size variation, modularity, and life‐history strategies in the skull from representatives of 35 mammalian families. We start by removing size variation from within‐species data and analyzing its influence on integration magnitudes, modularity patterns, and responses to selection. We also carry out a simulation in which we artificially alter the influence of size variation in within‐taxa matrices. Finally, we explore the relationship between size variation and different growth strategies. We demonstrate that a large portion of the evolution of modularity in the mammalian skull is associated to the evolution of growth strategies. Lineages with highly altricial neonates have adult variation patterns dominated by size variation, leading to high correlations among traits regardless of any underlying modular process and impacting directly their potential to respond to selection. Greater influence of size variation is associated to larger intermodule correlations, less individualized modules, and less flexible responses to natural selection.