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W R Atchley

Publications and source records attributed to W R Atchley.

At least 37 records · Page 2Linked to original sources
PubMed1997

Developmental quantitative genetics, conditional epigenetic variability and growth in mice.

Ontogenetic variation in the causal components of phenotypic variability and covariability is described for body weight and tail length in mice derived from a full 7 x 7 diallel cross. Age-related changes in additive, dominance, sex-linked and maternal variance and covariance between 14 and 70 days of age are described. Age-specific variance components at time t are conditioned on the causal genetic effects at time (t - 1). This procedure demonstrates the generation of significant episodes of new genetic variation arising at specific intervals during ontogeny. These episodes of new genetic variation are placed in the context of epigenetic models in developmental quantitative genetics. These results are also concordant on recent findings on age-specific gene expression in mouse growth as shown by QTL analyses.

Animals↗
PubMed1996

Mapping quantitative trait loci for complex binary diseases using line crosses.

A composite interval gene mapping procedure for complex binary disease traits is proposed in this paper. The binary trait of interest is assumed to be controlled by an underlying liability that is normally distributed. The liability is treated as a typical quantitative character and thus described by the usual quantitative genetics model. Translation from the liability into a binary (disease) phenotype is through the physiological threshold model. Logistic regression analysis is employed to estimate the effects and locations of putative quantitative trait loci (our terminology for a single quantitative trait locus is QTL while multiple loci are referred to as QTLs). Simulation studies show that properties of this mapping procedure mimic those of the composite interval mapping for normally distributed data. Potential utilization of the QTL mapping procedure for resolving alternative genetic models (e.g., single- or two-trait-locus model) is discussed.

Chromosome Mapping↗
PubMed1995

Myc and Max: molecular evolution of a family of proto-oncogene products and their dimerization partner.

The myc gene family encodes a group of transcription factors that regulate cell proliferation and differentiation. These genes are widely studied because of their importance as proto-oncogenes. Phylogenetic analyses are described here for 45 Myc protein sequences representing c-, N-, L-, S-, and B-myc genes. A gene duplication early in vertebrate evolution produced the c-myc lineage and another lineage that later gave rise to the N- and L-myc lineages by another gene duplication. Evolutionary divergence in the myc gene family corresponds closely to the known branching order of the major vertebrate groups. The patterns of sequence evolution are described for five separate highly conserved regions, and these analyses show that differential rates of sequence divergence (= mosaic evolution) have occurred among conserved motifs. Further, the closely related dimerization partner protein Max exhibits significantly less sequence variability than Myc. It is suggested that the reduced variability in max stems from natural selection acting to preserve dimerization capability with products of myc and related genes.

Amino Acid Sequence↗
PubMed1995

A random model approach to interval mapping of quantitative trait loci.

Mapping quantitative trait loci in outbred populations is important because many populations of organisms are noninbred. Unfortunately, information about the genetic architecture of the trait may not be available in outbred populations. Thus, the allelic effects of genes can not be estimated with ease. In addition, under linkage equilibrium, marker genotypes provide no information about the genotype of a QTL (our terminology for a single quantitative trait locus is QTL while multiple loci are referred to as QTLs). To circumvent this problem, an interval mapping procedure based on a random model approach is described. Under a random model, instead of estimating the effects, segregating variances of QTLs are estimated by a maximum likelihood method. Estimation of the variance component of a QTL depends on the proportion of genes identical-by-descent (IBD) shared by relatives at the locus, which is predicted by the IBD of two markers flanking the QTL. The marker IBD shared by two relatives are inferred from the observed marker genotypes. The procedure offers an advantage over the regression interval mapping in terms of high power and small estimation errors and provides flexibility for large sibships, irregular pedigree relationships and incorporation of common environmental and fixed effects.

Alleles↗
PubMed1995

Hormone gradients and cartilage cell kinetics.

We present a model of growth control in mammalian cartilage growth plates by hormones. The model is based on the distribution of insulin-like growth factors I and II (IGF-I and IGF-II) and their receptors, and assumes that a hormone-receptor complex of IGF controls cells proliferation. A system of differential equations is derived and solved with simplifications in extreme cases, for the one-dimensional time independent case. Even if opposite extremes, such as proliferation control by factors extrinsic to the cell versus intrinsic to the cell, are assumed, similar distributions of hormones and proliferating cells are produced. Hence, choice between alternative models of growth control must be based on empirical observations. On the positive side, similarities between our model for cartilage growth and other models for differentiation and proliferation are evident and might be exploited for unifying these systems on an abstract level.

Animals↗
PubMed1994

Molecular evolution of the MyoD family of transcription factors.

Myogenesis in skeletal muscle is a cascade of developmental events whose initiation involves the MyoD family of transcription factors. Evolutionary analyses of amino acid sequences of this family of transcriptional activators suggest that the vertebrate genes MyoD1, myf-5, Myog (myogenin), and myf-6 were derived by gene duplications from a single ancestral gene. A common genetic origin predicts some functional redundancy between MyoD1 and myf-5 and between Myog and myf-6. Experimental studies have suggested that these pairs of genes can substitute for each other during myogenesis. Separate analyses of the conserved basic helix-loop-helix and nonconserved flanking elements yield similar branching sequences but show evolutionary change in the basic helix-loop-helix region has occurred at a much slower rate.

Animals↗
PubMed1994

Developmental quantitative genetic models of evolutionary change.

Discussions about evolutionary change in developmental processes or morphological structures are predicated on specific quantitative genetic models whose parameters predict whether evolutionary change can occur, its relative rate and direction, and if correlated change will occur in other related and unrelated structures. The appropriate genetic model should reflect the relevant genetical and developmental biology of the organisms, yet be simple enough in its parameters so that deductions can be made and hypotheses tested. As a consequence, the choice of the most appropriate genetic model for polygenically controlled traits is a complex tissue and the eventual choice of model is often a compromise between completeness of the model and computational expediency. Herein, we discuss several developmental quantitative genetic models for the evolution of development and morphology. The models range from the classical direct effects model to complex epigenetic models. Further, we demonstrate the algebraic equivalency of the Cowley and Atchley epigenetic model and Wagner's developmental mapping model. Finally, we propose a new multivariate model for continuous growth trajectories. The relative efficacy of these various models for understanding evolutionary change in developmental and morphological traits is discussed.

Animals↗
PubMed1994

Phylogenetic inference under the pure drift model.

When pairwise genetic distances are used for phylogenetic reconstruction, it is usually assumed that the genetic distance between two taxa contains information about the time after the two taxa diverged. As a result, upon an appropriate transformation if necessary, the distance usually can be fitted to a linear model such that it is expressed as the sum of lengths of all branches that connect the two taxa in a given phylogeny. This kind of distance is referred to as "additive distance." For a phylogenetic tree exclusively driven by random genetic drift, genetic distances related to coancestry coefficients (theta XY) between any two taxa are more suitable. However, these distances are fundamentally different from the additive distance in that coancestry does not contain any information about the time after two taxa split from a common ancestral population; instead, it reflects the time before the two taxa diverged. In other words, the magnitude of theta XY provides information about how long the two taxa share the same evolutionary pathways. The fundamental difference between the two kinds of distances has led to a different algorithm of evaluating phylogenetic trees when theta XY and related distance measures are used. Here we present the new algorithm using the ordinary-least-squares approach but fitting to a different linear model. This treatment allows genetic variation within a taxon to be included in the model. Monte Carlo simulation for a rooted phylogeny of four taxa has verified the efficacy and consistency of the new method. Application of the method to human population was demonstrated.

Animals↗
PubMed1993

Genetic affinities of inbred mouse strains of uncertain origin.

Phylogenetic analyses of genetic data arising from 144 gene loci are used to describe the interrelationships among 24 widely used inbred strains of mice. An unordered-parsimony analysis gives a cladogram that is virtually identical to the known genealogy of the mouse strains. A loss-parsimony analysis is used to evaluate the hypothesis that the observed patterns of genetic divergence among these 24 strains can be explained by the segregation of residual heterozygosity arising from a small population of highly heterozygous mice. The loss-parsimony cladogram is very similar to both the unordered-parsimony cladogram and the known genealogy of the mice. The phylogenetic analyses of these 144 loci are integrated with data on the type and origin of the Y chromosome. Inclusion of the Y-chromosome data provides additional insights into the genetic composition of several of the original stocks used to produce the current inbred strains of mice. Ten strains of uncertain origin are contained in these analyses, including AKR, BUB, CE, I, NZB, P, RF, SJL, ST, and SWR. SJL is hypothesized to have been derived from the same Swiss albino stock previously used to produce SWR. The BUB strain appears to have had a complex origin and shows closest genetic similarity to SWR and ST. AKR and RF are shown to be closely related, while the I strain shows greatest genetic similarity to DBA/2 for the 144 loci. However, I and DBA possess different types of Y chromosome. The NZB strain shows genetic similarity to several stocks of both U.S. and European origins. The power of the genetic data used in these analyses reiterates that inbred strains of mice can be a valuable paradigm for studies in evolutionary biology.

Animals↗
PubMed1993

The epigenetic influence of growth hormone on skeletal development.

We studied the epigenetic effect of growth hormone using mice that were transgenic for a sheep metallothionein 1a-sheep growth hormone, which was expressed beginning at 21 days postnatal age. The impact of exogenous growth hormone (GH) on various skeletal traits with special emphasis on the mandible was examined by conventional statistical analysis and finite element scaling analysis. In long bones, growth hormone enhances the proliferation rate of cartilage cells in the growth plate and should thus lead to increased lengths. Further, growth hormone is known to increase muscle mass. Our results are consistent with these developmental considerations. We found that the lengths of long bones increased in the transgenic mice compared to the control mice, while the differences in long bone width were less pronounced. In the mandible and skull, the impact of GH is most pronounced in areas of major muscle attachment, i.e., the proximal part of the mandible and the occipital and malar bones in the skull.

Animals↗
PubMed1991

Gene trees and the origins of inbred strains of mice.

Extensive data on genetic divergence among 24 inbred strains of mice provide an opportunity to examine the concordance of gene trees and species trees, especially whether structured subsamples of loci give congruent estimates of phylogenetic relationships. Phylogenetic analyses of 144 separate loci reproduce almost exactly the known genealogical relationships among these 24 strains. Partitioning these loci into structured subsets representing loci coding for proteins, the immune system and endogenous viruses give incongruent phylogenetic results. The gene tree based on protein loci provides an accurate picture of the genealogical relationships among strains; however, gene trees based upon immune and viral data show significant deviations from known genealogical affinities.

Algorithms↗
PubMed1991

A model for development and evolution of complex morphological structures.

How 'complex' or composite morphological structures like the mammalian craniomandibular region arise during development and how they are altered during evolution are two major unresolved questions in biology. Herein, we have described a model for the development and evolution of complex morphological structures. The model assumes that natural selection acts upon an array of phenotypes generated by variation in a variety of underlying genetic and epigenetic controlling factors. Selection refines the integration of the various morphogenetic components during ontogeny in order to produce a functioning structure and to adapt the organisms to differing patterns of environmental heterogeneity. The model was applied to the development and evolution of the mammalian mandible (which is used as a paradigm of complex morphological structures). The embryology of the mandible was examined in detail in order to identify the fundamental developmental units which are necessary to assemble the final morphological structure. The model is quite general since equivalent units exist for the development of many other biological structures. This model could be applied to many other developing morphological structures as well as other groups of organisms. For example, it can be applied to cell parameters during Drosophila development (Atchley, 1987). The model as discussed in this paper assumes that morphological changes in the mandible result from evolutionary changes in its underlying developmental units. The developmental units relate to characteristics of cellular condensations which are produced from the differentiation of embryonic neural crest cells. The developmental units include: the number of stem cells in preskeletal condensations (n), the time of initiation of condensation formation (t), the fraction of cells that is mitotically active within a condensation (f), the rate of division of these cells (r), and their rate of cell death (d). These units and their derivative structures are discussed in terms of types of tissue differentiation (chondrogenesis, osteogenesis, primary/secondary osteogenesis, intramembranous/endochondral ossification) and growth properties of major morphological regions of the mandible. Variation in these five units provides the developmental basis for ontogenetic and phylogenetic modification of mandibular morphology. We have discussed how these developmental units are influenced by (a) the cell lineage from which they arise, (b) epithelial-mesenchymal (inductive tissue) interactions, (c) regulation of cell differentiation, and (d) extrinsic factors such as muscles, teeth and hormones. Evidence was provided that variation in mandibular morphology is heritable, subject to modification by natural selection, and that divergence among different genetic stocks has apparently occurred through changes in these developmental units and their derivative structures.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

The impact of maternal uterine genotype on postnatal growth and adult body size in mice.

Embryo transfers were used to demonstrate that the genotype of the mother providing the uterine developmental environment significantly influences postnatal growth and adult body size of her progeny. Irrespective of their own genotype, mouse embryos transferred into the uterus of an inbred strain with large body size (C3H) had greater body weights, longer tails and higher growth rates than those transferred into the uterus of a strain with small body size (SWR). Uterine heterosis on body size was smaller than progeny heterosis, and both progeny and uterine heterosis persisted in adult mice. Uterine litter size was significantly negatively associated with body weight, tail length, growth rate and the timing of developmental events. The inbred SWR strain was more sensitive to the embryo transfer procedure than the C3H strain, but effects due to embryo transfer were moderate. Prenatal uterine effects have ramifications for biotechnologies utilizing embryo transfer as well as predictions about evolutionary change by selection.

Analysis of Variance↗
PubMed1989

Donor and recipient genotype and heterosis effects on survival and prenatal growth of transferred mouse embryos.

Reciprocal embryo transfers amongst two inbred strains (C3HeB/FeJ and SWR/J) and their F1 cross (C3SWF1) were used to examine donor and recipient genotype and heterosis effects on survival and prenatal growth of mouse embryos. Among inbred strains, significant recipient genotype effects were detected for both embryo survival (P less than 0.01) and prenatal growth (P less than 0.05), while no donor genotype effects were observed. The recipient effect on overall embryo survival was due to a higher proportion of C3H recipients maintaining pregnancy to term than SWR recipients (P less than 0.01), rather than survival within litters. Irrespective of their own genotype, embryos developing in C3H uteri achieved larger body weights (P less than 0.01) and longer tail lengths (P less than 0.05) at birth than did embryos developing in SWR uteri. Recipient heterosis was not significant, while donor heterosis was significant for prenatal growth traits (P less than 0.001).

Animals↗
PubMed1988

Genetic divergence in mandible form in relation to molecular divergence in inbred mouse strains.

Genetic divergence in the form of the mandible is examined in ten inbred strains of mice. Several univariate and multivariate genetic distance estimates are given for the morphological data and these estimates are compared to measures of genealogical and molecular divergence. Highly significant divergence occurs among the ten strains in all 11 mandible traits considered individually and simultaneously. Genealogical relationship among strains is highly correlated with genetic divergence in single locus molecular traits. However, the concordance between genealogical relationship and multivariate genetic divergence in morphology is much more complex. Whether there is a significant correlation between morphological divergence and genealogy depends upon the method of analysis and the particular genetic distance statistic being employed.

Animals↗
PubMed1985

Evolution in inbred strains of mice appears rapid.

Genetic variation at 97 loci in ten commonly used inbred strains of mice is greatly in excess of that expected under current assumptions. Evidence against all of the readily apparent explanations is presented and the possibility of early selection for heterozygosity or of conversion is suggested. The common ancestor of these strains is estimated to have occurred about 150 years ago.

Animals↗
PubMed1985

Genetics of mandible form in the mouse.

The underlying determination of phenotypic variability and covariability is described for 14 traits that define the morphological size and shape of the mature mouse mandible. Variability is partitioned into components due to direct additive and dominance genetic effects, indirect maternal additive genetic effects, genetic covariance between direct additive and indirect maternal additive effects and common and residual environmental effects. Multivariate analyses of the dimensionality of genetic variability indicate several complex and independent genetic components underlie the morphological form of the mandible. The multidimensional nature of the genetic components suggests a complex picture with regard to the consequences of selection on mandibular form.

Analysis of Variance↗