@article{mcferrin_atchley_2012, title={A novel N-terminal domain may dictate the glucose response of Mondo proteins}, volume={7}, number={4}, journal={PLoS One}, author={McFerrin, L. G. and Atchley, W. R.}, year={2012} }
 @article{mcferrin_atchley_2011, title={Evolution of the Max and Mlx Networks in Animals}, volume={3}, ISSN={["1759-6653"]}, DOI={10.1093/gbe/evr082}, abstractNote={Transcription factors (TFs) are essential for the regulation of gene expression and often form emergent complexes to perform vital roles in cellular processes. In this paper, we focus on the parallel Max and Mlx networks of TFs because of their critical involvement in cell cycle regulation, proliferation, growth, metabolism, and apoptosis. A basic-helix-loop-helix-zipper (bHLHZ) domain mediates the competitive protein dimerization and DNA binding among Max and Mlx network members to form a complex system of cell regulation. To understand the importance of these network interactions, we identified the bHLHZ domain of Max and Mlx network proteins across the animal kingdom and carried out several multivariate statistical analyses. The presence and conservation of Max and Mlx network proteins in animal lineages stemming from the divergence of Metazoa indicate that these networks have ancient and essential functions. Phylogenetic analysis of the bHLHZ domain identified clear relationships among protein families with distinct points of radiation and divergence. Multivariate discriminant analysis further isolated specific amino acid changes within the bHLHZ domain that classify proteins, families, and network configurations. These analyses on Max and Mlx network members provide a model for characterizing the evolution of TFs involved in essential networks.}, journal={GENOME BIOLOGY AND EVOLUTION}, author={McFerrin, Lisa G. and Atchley, William R.}, year={2011}, pages={915–937} }
 @article{fronza_tramonti_atchley_nardini_2011, title={Joint analysis of transcriptional and post-transcriptional brain tumor data: searching for emergent properties of cellular systems}, volume={12}, journal={BMC Bioinformatics}, author={Fronza, R. and Tramonti, M. and Atchley, W. R. and Nardini, C.}, year={2011} }
 @article{atchley_2011, title={Walter M. Fitch (1929-2011)}, volume={332}, ISSN={["0036-8075"]}, DOI={10.1126/science.1207426}, abstractNote={A meticulous biologist developed fundamental tools for the field of molecular evolution. Walter Monroe Fitch, founder of the field of molecular phylogenetics, passed away in Irvine, California, on 10 March at the age of 81. He was active until the time of his death, just finishing a book on the creationism-evolution controversy. He strongly promoted the widespread teaching of evolution.}, number={6031}, journal={SCIENCE}, author={Atchley, William R.}, year={2011}, month={May}, pages={804–804} }
 @article{fernandes_atchley_2008, title={Biochemical and functional evidence of p53 homology is inconsistent with molecular phylogenetics for distant sequences}, volume={67}, ISSN={["0022-2844"]}, DOI={10.1007/s00239-008-9124-2}, number={1}, journal={JOURNAL OF MOLECULAR EVOLUTION}, author={Fernandes, Andrew D. and Atchley, William R.}, year={2008}, month={Jul}, pages={51–67} }
 @article{funk-keenan_haire_woolard_atchley_2008, title={Hepatic endopolyploidy as a cellular consequence of age-specific selection for rate of development in mice}, volume={310B}, ISSN={["1552-5007"]}, DOI={10.1002/jez.b.21211}, abstractNote={Endopolyploidy is the generation of polyploid cells by DNA replication without subsequent cell division and is correlated with hypertrophic growth or growth via cell size. Thus, selection that alters growth may also change onset and frequency of endopolyploidy as a correlated response. We search for endopolyploidy in the liver in response to age-specific restricted index selection for the rate of development. Polyploidy changes over ontogeny are described in five mouse lines: two selected for divergence in early growth (0-10 days of age), two selected for divergence in late growth (28-56 days of age), and one randombred control. Polyploid cell frequency within each line increased as ontogeny continued, as expected from previous research. However, selection for altered growth clearly plays a role in the frequency and onset of polyploid cells. Lines selected for divergence in early growth have polyploidy differences after weaning that are not seen in adult mice. However, lines selected for divergence in late growth are divergent in frequency of polyploid cells, starting near sexual maturity and continuing into adulthood.}, number={5}, journal={JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION}, author={Funk-Keenan, Jhondra and Haire, Frances and Woolard, Sara and Atchley, William R.}, year={2008}, month={Jul}, pages={385–397} }
 @article{fernandes_atchley_2008, title={Site-specific evolutionary rates in proteins are better modeled as non-independent and strictly relative}, volume={24}, ISSN={["1460-2059"]}, DOI={10.1093/bioinformatics/btn395}, abstractNote={MOTIVATION
In a nucleotide or amino acid sequence, not all sites evolve at the same rate, due to differing selective constraints at each site. Currently in computational molecular evolution, models incorporating rate heterogeneity always share two assumptions. First, the rate of evolution at each site is assumed to be independent of every other site. Second, the values of these rates are assumed to be drawn from a known prior distribution. Although often assumed to be small, the actual effect of these assumptions has not been previously quantified in the literature.


RESULTS
Herein we describe an algorithm to simultaneously infer the set of n-1 relative rates that parameterize the likelihood of an n-site alignment. Unlike previous work (a) these relative rates are completely identifiable and distinct from the branch-length parameters, and (b) a far more general class of rate priors can be used, and their effects quantified. Although described in a Bayesian framework, we discuss a future maximum likelihood extension.


CONCLUSIONS
Using both synthetic data and alignments from the Myc, Max and p53 protein families, we find that inferring relative rather than absolute rates has several advantages. First, both empirical likelihoods and Bayes factors show strong preference for the relative-rate model, with a mean Delta ln P=-0.458 per alignment site. Second, the computed likelihoods and Bayes factors were essentially independent of the relative-rate prior, indicating that good estimates of the posterior rate distribution are not required a priori. Third, a novel finding is that rates can be accurately inferred even when up to approximately 4 substitutions per site have occurred. Thus biologically relevant putative hypervariable sites can be identified as easily as conserved sites. Lastly, our model treats rates and tree branch-lengths as completely identifiable, allowing for the first time coherent simultaneous inference of branch-lengths and site-specific evolutionary rates.


AVAILABILITY
Source code for the utility described is available under a BSD-style license at http://www.fernandes.org/txp/article/9/site-specific-relative-evolutionary-rates.}, number={19}, journal={BIOINFORMATICS}, author={Fernandes, Andrew D. and Atchley, William R.}, year={2008}, month={Oct}, pages={2177–2183} }
 @article{wang_smith_atchley_2007, title={Application of complex demodulation on bZIP and bHLH-PAS protein domains}, volume={207}, DOI={10.1016/j.mbs.2007.01.004}, abstractNote={Proteins are built with molecular modular building blocks such as an alpha-helix, beta-sheet, loop region and other structures. This is an economical way of constructing complex molecules. Periodicity analysis of protein sequences has allowed us to obtain meaningful information concerning their structure, function and evolution. In this work, complex demodulation (CDM) is introduced to detect functional regions in protein sequences data. More specifically, we analyzed bZIP and bHLH-PAS protein domains. Complex demodulation provided insightful information about changing amplitudes of periodic components in protein sequences. Furthermore, it was found that the local amplitude minimum or local amplitude maximum of the 3.6-aa periodic component is associated with protein structural or functional information due to the observation that the extrema are mainly located in the boundary area of two structural or functional regions.}, number={2}, journal={Mathematical Biosciences}, author={Wang, Z. and Smith, C. E. and Atchley, W. R.}, year={2007}, pages={204–218} }
 @article{atchley_zhao_2007, title={Molecular architecture of the DNA-binding region and its relationship to classification of basic helix-loop-helix proteins}, volume={24}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msl143}, abstractNote={Multivariate statistical analyses are used to explore the molecular architecture of the DNA-binding and dimerization regions of basic helix-loop-helix (bHLH) proteins. Alphabetic amino acid data are transformed to biologically meaningful quantitative values using a set of 5 multivariate "indices." These multivariate indices summarize variation in a large suite of amino acid physiochemical attributes and reflect variability in polarity-accessibility-hydrophobicity, propensity for secondary structure, molecular size, codon composition, and electrostatic charge. Using these index score data, discriminant analyses describe the multidimensional aspects of physiochemical variation and clarify the structural basis of the prevailing evolutionary classification of bHLH proteins. A small number of amino acids from both the binding dimerization domains, when considered simultaneously, accurately distinguish the 5 known DNA-binding groups. The relevant sites often have well-documented structural and functional characteristics.}, number={1}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Atchley, William R. and Zhao, Jieping}, year={2007}, month={Jan}, pages={192–202} }
 @article{buck_atchley_2005, title={Networks of coevolving sites in structural and functional domains of serpin proteins}, volume={22}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msi157}, abstractNote={Amino acids do not occur randomly in proteins; rather, their occurrence at any given site is strongly influenced by the amino acid composition at other sites, the structural and functional aspects of the region of the protein in which they occur, and the evolutionary history of the protein. The goal of our research study is to identify networks of coevolving sites within the serpin proteins (serine protease inhibitors) and classify them as being caused by structural-functional constraints or by evolutionary history. To address this, a matrix of pairwise normalized mutual information (NMI) values was computed among amino acid sites for the serpin proteins. The NMI matrix was partitioned into orthogonal patterns of amino acid variability by factor analysis. Each common factor pattern was interpreted as having phylogenetic and/or structural-functional explanations. In addition, we used a bootstrap factor analysis technique to limit the effects of phylogenetic history on our factor patterns. Our results show an extensive network of correlations among amino acid sites in key functional regions (reactive center loop, shutter, and breach). Additionally, we have discovered long-range coevolution for packed amino acids within the serpin protein core. Lastly, we have discovered a group of serpin sites which coevolve in the hydrophobic core region (s5B and s4B) and appear to represent sites important for formation of the "native" instead of the "latent" serpin structure. This research provides a better understanding on how protein structure evolves; in particular, it elucidates the selective forces creating coevolution among protein sites.}, number={7}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Buck, MJ and Atchley, WR}, year={2005}, month={Jul}, pages={1627–1634} }
 @article{atchley_fernandes_2005, title={Sequence signatures and the probabilistic identification of proteins in the Myc-Max-Mad network}, volume={102}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0408964102}, abstractNote={Accurate identification of specific groups of proteins by their amino acid sequence is an important goal in genome research. Here we combine information theory with fuzzy logic search procedures to identify sequence signatures or predictive motifs for members of the Myc-Max-Mad transcription factor network. Myc is a well known oncoprotein, and this family is involved in cell proliferation, apoptosis, and differentiation. We describe a small set of amino acid sites from the N-terminal portion of the basic helix-loop-helix (bHLH) domain that provide very accurate sequence signatures for the Myc-Max-Mad transcription factor network and three of its member proteins. A predictive motif involving 28 contiguous bHLH sequence elements found 337 network proteins in the GenBank NR database with no mismatches or misidentifications. This motif also identifies at least one previously unknown fungal protein with strong affinity to the Myc-Max-Mad network. Another motif found 96% of known Myc protein sequences with only a single mismatch, including sequences from genomes previously not thought to contain Myc proteins. The predictive motif for Myc is very similar to the ancestral sequence for the Myc group estimated from phylogenetic analyses. Based on available crystal structure studies, this motif is discussed in terms of its functional consequences. Our results provide insight into evolutionary diversification of DNA binding and dimerization in a well characterized family of regulatory proteins and provide a method of identifying signature motifs in protein families.}, number={18}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Atchley, WR and Fernandes, AD}, year={2005}, month={May}, pages={6401–6406} }
 @article{atchley_zhao_fernandes_druke_2005, title={Solving the protein sequence metric problem}, volume={102}, ISSN={["1091-6490"]}, DOI={10.1073/pnas.0408677102}, abstractNote={Biological sequences are composed of long strings of alphabetic letters rather than arrays of numerical values. Lack of a natural underlying metric for comparing such alphabetic data significantly inhibits sophisticated statistical analyses of sequences, modeling structural and functional aspects of proteins, and related problems. Herein, we use multivariate statistical analyses on almost 500 amino acid attributes to produce a small set of highly interpretable numeric patterns of amino acid variability. These high-dimensional attribute data are summarized by five multidimensional patterns of attribute covariation that reflect polarity, secondary structure, molecular volume, codon diversity, and electrostatic charge. Numerical scores for each amino acid then transform amino acid sequences for statistical analyses. Relationships between transformed data and amino acid substitution matrices show significant associations for polarity and codon diversity scores. Transformed alphabetic data are used in analysis of variance and discriminant analysis to study DNA binding in the basic helix-loop-helix proteins. The transformed scores offer a general solution for analyzing a wide variety of sequence analysis problems.}, number={18}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Atchley, WR and Zhao, JP and Fernandes, AD and Druke, T}, year={2005}, month={May}, pages={6395–6400} }
 @article{buck_atchley_2003, title={Phylogenetic analysis of plant basic helix-loop-helix proteins}, volume={56}, DOI={10.1007/s00239-002-2449-3}, number={6}, journal={Journal of Molecular Evolution}, author={Buck, M. J. and Atchley, W. R.}, year={2003}, pages={742–750} }
 @article{johnson_wolff_wernsman_atchely_shew_2002, title={Origin of the black shank resistance gene, Ph, in tobacco cultivar Coker 371-gold}, volume={86}, ISSN={["0191-2917"]}, DOI={10.1094/PDIS.2002.86.10.1080}, abstractNote={Flue-cured tobacco (Nicotiana tabacum) cultivar Coker 371-Gold (C 371-G) possesses a dominant gene, Ph, that confers high resistance to black shank disease, caused by race 0 of the soil-borne pathogen Phytophthora parasitica var. nicotianae. The origin of this gene is unknown. Breeding lines homozygous for the Ph gene were hybridized with NC 1071 and L8, flue-cured and burley genotypes known to possess qualitative resistance genes from Nicotiana plumbaginifolia and N. longiflora, respectively. The F1 hybrids were out-crossed to susceptible testers and the progenies evaluated in field black shank nurseries and in greenhouse disease tests with P. parasitica var. nicotianae race 0. Results showed that Ph was allelic to Php from N. plumbaginifolia in NC 1071. Testcross populations of hybrids between burley lines homozygous for Ph and L8, possessing Phl from N. longiflora, showed that Ph and Phl integrated into the same tobacco chromosome during interspecific transfer. Nevertheless, the two loci were estimated to be 3 cM apart. Random amplified polymorphic DNA (RAPD) analyses of the testcross progenies confirmed that recombination between the two loci was occurring. Forty-eight RAPD markers linked to Ph in doubled haploid lines were used in cluster analyses with multiple accessions of N. longiflora and N. plumbaginifolia, breeding lines L8, NC 1071, and DH92-2770-40, and cultivars K 326, Hicks, and C 371-G. A cladogram or region tree confirmed the data obtained from field and greenhouse trials, that Ph, transferred from C 371-G to DH92-2770-40, and Php in NC 1071 were allelic and originated from N. plumbaginifolia.}, number={10}, journal={PLANT DISEASE}, author={Johnson, ES and Wolff, MF and Wernsman, EA and Atchely, WR and Shew, HD}, year={2002}, month={Oct}, pages={1080–1084} }
 @article{atchley_lokot_wollenberg_dress_ragg_2001, title={Phylogenetic analyses of amino acid variation in the serpin proteins}, volume={18}, ISSN={["1537-1719"]}, DOI={10.1093/oxfordjournals.molbev.a003936}, abstractNote={Phylogenetic analyses of 110 serpin protein sequences revealed clades consistent with independent phylogenetic analyses based on exon-intron structure and diagnostic amino acid sites. Trees were estimated by maximum likelihood, neighbor joining, and partial split decomposition using both the BLOSUM 62 and Jones-Taylor-Thornton substitution matrices. Neighbor-joining trees gave results closest to those based on independent analyses using genomic and chromosomal data. The maximum-likelihood trees derived using the quartet puzzling algorithm were very conservative, producing many small clades that separated groups of proteins that other results suggest were related. Independent analyses based on exon-intron structure suggested that a neighbor-joining tree was more accurate than maximum-likelihood trees obtained using the quartet puzzling algorithm.}, number={8}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Atchley, WR and Lokot, T and Wollenberg, K and Dress, A and Ragg, H}, year={2001}, month={Aug}, pages={1502–1511} }
 @article{ragg_lokot_kamp_atchley_dress_2001, title={Vertebrate serpins: Construction of a conflict-free phylogeny by combining exon-intron and diagnostic site analyses}, volume={18}, ISSN={["1537-1719"]}, DOI={10.1093/oxfordjournals.molbev.a003838}, abstractNote={A combination of three independent biological features, genomic organization, diagnostic amino acid sites, and rare indels, was used to elucidate the phylogeny of the vertebrate serpin (serine protease inhibitor) superfamily. A strong correlation between serpin gene families displaying (1) a conserved exon-intron pattern and (2) family-specific combinations of amino acid residues at specific sites suggests that present-day vertebrates encompass six serpin gene families which evolved from primordial genes by massive intron insertion before or during early vertebrate radiation. Introns placed at homologous positions in the gene sequences in combination with diagnostic sequence characters may also constitute a reliable kinship indicator for other protein superfamilies.}, number={4}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Ragg, H and Lokot, T and Kamp, PB and Atchley, WR and Dress, A}, year={2001}, month={Apr}, pages={577–584} }
 @article{rhees_atchley_2000, title={Body weight and tail length divergence in mice selected for rate of development}, volume={288}, ISSN={["0022-104X"]}, DOI={10.1002/1097-010X(20000815)288:2<151::AID-JEZ6>3.0.CO;2-6}, abstractNote={A series of mouse lines has been produced by 19 generations of restricted index selection for rate of development during early and late ontogeny. The selection program was based on an index with the following four replicated selection treatments: E(+) and E(-) were selected to alter birth to 10-day body weight gain while holding late gain for both selection lines constant; correspondingly, L(+) and L(-) were selected to alter 28- to 56-day body weight gain holding early gain for both lines constant. Herein, we characterize response to selection for growth rate by analyzing age-specific mouse body weight and tail lengths and for growth curves using a logistics model. Selection on developmental rate has resulted in divergence in both age-specific and growth curve traits. E(+) and L(+) lines reached identical weights during the late selection interval, then diverged to unique mature weights. E(-) and L(-) lines similarly achieved identical weights during late selection and diverged to unique mature weights. However, the shapes of early and late growth curves were significantly divergent, and at least two distinct growth patterns are shown to result from selection. Response in body weight gain was accompanied by similar, though less pronounced, change in tail length traits. Significant response during intervals of restricted growth was also found, especially in lines selected for late gain. The evolution of the growth trajectory under restricted index selection is discussed in terms of drift and available additive genetic variation and covariation.}, number={2}, journal={JOURNAL OF EXPERIMENTAL ZOOLOGY}, author={Rhees, BK and Atchley, WR}, year={2000}, month={Aug}, pages={151–164} }
 @article{atchley_wei_crenshaw_2000, title={Cellular consequences in the brain and liver of age-specific selection for rate of development in mice}, volume={155}, number={3}, journal={Genetics}, author={Atchley, W. R. and Wei, R. and Crenshaw, P.}, year={2000}, pages={1347–1357} }
 @article{kulkarni_karavanich_atchley_anholt_2000, title={Characterization and differential expression of a human gene family of olfactomedin-related proteins}, volume={76}, ISSN={["0016-6723"]}, DOI={10.1017/S0016672300004584}, abstractNote={Olfactomedin-related proteins are secreted glycoproteins with conserved C-terminal motifs. Olfactomedin was originally identified as the major component of the mucus layer that surrounds the chemosensory dendrites of olfactory neurons. Homologues were subsequently found also in other tissues, including the brain and in species ranging from Caenorhabditis elegans to Homo sapiens. Most importantly, the TIGR/myocilin protein, expressed in the eye and associated with the pathogenesis of glaucoma, is an olfactomedin-related protein. The prevalence of olfactomedin-related proteins among species and their identification in different tissues prompted us to investigate whether a gene family exists within a species, specifically Homo sapiens. A GenBank search indeed revealed an entire human gene family of olfactomedin-related proteins with at least five members, designated hOlfA through hOlfD and the TIGR/myocilin protein. hOlfA corresponds to the rat neuronal AMZ protein. Phylogenetic analyses of 18 olfactomedin-related sequences resolved four distinct subfamilies. Among the human proteins, hOlfA and hOlfC, both expressed in brain, are most closely related. Northern blot analyses of 16 human tissues demonstrated highly specific expression patterns: hOlfA is expressed in brain, hOlfB in pancreas and prostate, hOlfC in cerebellum, hOlfD in colon, small intestine and prostate and TIGR/myocilin in heart and skeletal muscle. The link between TIGR/myocilin and ocular hypertension and the expression of several of these proteins in mucus-lined tissues suggest that they play an important role in regulating physical properties of the extracellular environment. Future studies can now assess whether other members of this gene family, like TIGR/myocilin, are also associated with human disease processes.}, number={1}, journal={GENETICAL RESEARCH}, author={Kulkarni, NH and Karavanich, CA and Atchley, WR and Anholt, RRH}, year={2000}, month={Aug}, pages={41–50} }
 @article{atchley_wollenberg_fitch_terhalle_dress_2000, title={Correlations among amino acid sites in bHLH protein domains: An information theoretic analysis}, volume={17}, ISSN={["0737-4038"]}, DOI={10.1093/oxfordjournals.molbev.a026229}, abstractNote={An information theoretic approach is used to examine the magnitude and origin of associations among amino acid sites in the basic helix-loop-helix (bHLH) family of transcription factors. Entropy and mutual information values are used to summarize the variability and covariability of amino acids comprising the bHLH domain for 242 sequences. When these quantitative measures are integrated with crystal structure data and summarized using helical wheels, they provide important insights into the evolution of three-dimensional structure in these proteins. We show that amino acid sites in the bHLH domain known to pack against each other have very low entropy values, indicating little residue diversity at these contact sites. Noncontact sites, on the other hand, exhibit significantly larger entropy values, as well as statistically significant levels of mutual information or association among sites. High levels of mutual information indicate significant amounts of intercorrelation among amino acid residues at these various sites. Using computer simulations based on a parametric bootstrap procedure, we are able to partition the observed covariation among various amino acid sites into that arising from phylogenetic (common ancestry) and stochastic causes and those resulting from structural and functional constraints. These results show that a significant amount of the observed covariation among amino acid sites is due to structural/functional constraints, over and above the covariation arising from phylogenetic constraints. These quantitative analyses provide a highly integrated evolutionary picture of the multidimensional dynamics of sequence diversity and protein structure.}, number={1}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Atchley, WR and Wollenberg, KR and Fitch, WM and Terhalle, W and Dress, AW}, year={2000}, month={Jan}, pages={164–178} }
 @article{miller_chrisp_atchley_2000, title={Differential longevity in mouse stocks selected for early life growth trajectory}, volume={55}, ISSN={["1079-5006"]}, DOI={10.1093/gerona/55.9.b455}, abstractNote={Small body size is associated with superior longevity in several intraspecies comparisons, including dogs bred for specific forms of work, mice and rats fed diets low in calories, rats fed diets low in methionine, and mutant mice whose levels of growth hormone and thyroid hormone are atypically low. To further investigate the interactions among body size, genetic endowment, and longevity, we measured the life span of female mice selectively bred from Institute for Cancer Research stock for differences in rate of body weight gain. These mice were selected for differential rates of growth either early (0-10 days) or later (26-56 days) in the first 2 months of life. The data show a good correlation between the average weight of the stock and its mean longevity, with low body size associated, as predicted, with longer life span. Weight at 3, 6, and 12 months, and weight at peak body weight, are all significant predictors of longevity (among stocks) in univariate regressions; weight at 6 months has the strongest association in stepwise multiple regression. There is no significant correlation between the life span for the stock and the proportion of deaths attributable to neoplasia in this group of mice. The data provide support for the hypothesis that genetic factors that influence early life growth trajectories can have a strong influence on life span. These size-selected mice provide useful tools for analysis of the genetic factors that influence life history parameters, including maturation and aging rates.}, number={9}, journal={JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES}, author={Miller, RA and Chrisp, C and Atchley, W}, year={2000}, month={Sep}, pages={B455–B461} }
 @article{ernst_rhees_miao_atchley_2000, title={Effect of long-term selection for early postnatal growth rate on survival and prenatal development of transferred mouse embryos}, volume={118}, number={1}, journal={Journal of Reproduction & Fertility}, author={Ernst, C. A. and Rhees, B. K. and Miao, C. H. and Atchley, W. R.}, year={2000}, pages={205–210} }
 @article{lowry_atchley_2000, title={Molecular evolution of the GATA family of transcription factors: Conservation within the DNA-binding domain}, volume={50}, ISSN={["1432-1432"]}, DOI={10.1007/s002399910012}, number={2}, journal={JOURNAL OF MOLECULAR EVOLUTION}, author={Lowry, JA and Atchley, WR}, year={2000}, month={Feb}, pages={103–115} }
 @article{wollenberg_atchley_2000, title={Separation of phylogenetic and functional associations in biological sequences by using the parametric bootstrap}, volume={97}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.070154797}, abstractNote={Quantitative analyses of biological sequences generally proceed under the assumption that individual DNA or protein sequence elements vary independently. However, this assumption is not biologically realistic because sequence elements often vary in a concerted manner resulting from common ancestry and structural or functional constraints. We calculated intersite associations among aligned protein sequences by using mutual information. To discriminate associations resulting from common ancestry from those resulting from structural or functional constraints, we used a parametric bootstrap algorithm to construct replicate data sets. These data are expected to have intersite associations resulting solely from phylogeny. By comparing the distribution of our association statistic for the replicate data against that calculated for empirical data, we were able to assign a probability that two sites covaried resulting from structural or functional constraint rather than phylogeny. We tested our method by using an alignment of 237 basic helix–loop–helix (bHLH) protein domains. Comparison of our results against a solved three-dimensional structure confirmed the identification of several sites important to function and structure of the bHLH domain. This analytical procedure has broad utility as a first step in the identification of sites that are important to biological macromolecular structure and function when a solved structure is unavailable. Sign up for PNAS alerts. Get alerts for new articles, or get an alert when an article is cited. Manage alerts}, number={7}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Wollenberg, KR and Atchley, WR}, year={2000}, month={Mar}, pages={3288–3291} }
 @article{ernst_crenshaw_atchley_1999, title={Effect of selection for development rate on reproductive onset in female mice}, volume={74}, ISSN={["0016-6723"]}, DOI={10.1017/S001667239900381X}, abstractNote={This research reports analyses of correlated response in reproductive onset in ICR mice after 23 generations of restricted index selection for divergent body weight gain, early (birth-10 days) or later (28-56 days) in life. Long-term selection altered growth trajectories and 56 day body weight of individuals under different selection regimes in this study. Mice in lines under early selection have the same percentage mature weight at vaginal opening as controls (63%). Vaginal opening is delayed in mice selected for slow early growth, which take longer to reach what appears to be a weight threshold. In contrast, individuals in lines selected for later slow growth undergo vaginal opening at the same age as controls, but at a lower weight and increased percentage mature weight. Pre-compensation or 'counter-balance growth' is observed in these lines, with mice selected for late enhanced growth reaching 52% of mature weight at vaginal opening while mice with late slow growth attain 71% of mature weight prior to vaginal opening. Only 42% of mice with late slow growth attain first oestrus by 56 days. We speculate this is a function of growth rate and fat/lean ratio. Mice with early slow growth show compensatory growth, reaching first oestrus at a similar time to controls. We conclude that selection for growth rate has asymmetrically affected reproductive onset, with lines selected for suppressed gains experiencing delays in the reproductive onset traits measured.}, number={1}, journal={GENETICAL RESEARCH}, author={Ernst, CA and Crenshaw, PD and Atchley, WR}, year={1999}, month={Aug}, pages={55–64} }
 @article{morgenstern_atchley_1999, title={Evolution of bHLH transcription factors: Modular evolution by domain shuffling?}, volume={16}, ISSN={["1537-1719"]}, DOI={10.1093/oxfordjournals.molbev.a026079}, abstractNote={Multidomain proteins usually contain several conserved and apparently independently evolved domains. As a result, classifications based on only a single small domain may obscure the true evolutionary relationships of the proteins. The current classification of basic helix-loop-helix (bHLH) domain-containing proteins is based on the conserved bHLH domain alone. Herein, we explore whether sequence homology and, therefore, evolutionary relationships can be detected among the flanking or non-bHLH components of the amino acid sequences of 122 bHLH proteins. These 122 proteins were the same proteins previously used to construct the existing classification of the bHLH-domain-containing proteins. Several possible scenarios are examined in order to explain the observed patterns of sequence divergence, including (1) monophyly, (2) convergent evolution, (3) addition of functional components to the bHLH domain, and (4) modular evolution with domain shuffling. Drawing on several lines of evidence, we suggest that modular evolution by domain shuffling may have played an important role in the evolution of this large group of transcriptional regulators.}, number={12}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Morgenstern, B and Atchley, WR}, year={1999}, month={Dec}, pages={1654–1663} }
 @article{rosinski_atchley_1999, title={Molecular evolution of helix-turn-helix proteins}, volume={49}, ISSN={["0022-2844"]}, DOI={10.1007/PL00006552}, number={3}, journal={JOURNAL OF MOLECULAR EVOLUTION}, author={Rosinski, JA and Atchley, WR}, year={1999}, month={Sep}, pages={301–309} }
 @article{atchley_terhalle_dress_1999, title={Positional dependence, cliques, and predictive motifs in the bHLH protein domain}, volume={48}, ISSN={["0022-2844"]}, DOI={10.1007/PL00006494}, number={5}, journal={JOURNAL OF MOLECULAR EVOLUTION}, author={Atchley, WR and Terhalle, W and Dress, A}, year={1999}, month={May}, pages={501–516} }
 @article{rhees_ernst_miao_atchley_1999, title={Uterine and postnatal maternal effects in mice selected for differential rate of early development}, volume={153}, number={2}, journal={Genetics}, author={Rhees, B. K. and Ernst, C. A. and Miao, C. H. and Atchley, W. R.}, year={1999}, pages={905–917} }
 @article{rosinski_atchley_1998, title={Molecular evolution of the Myb family of transcription factors: Evidence for polyphyletic origin}, volume={46}, ISSN={["1432-1432"]}, DOI={10.1007/PL00006285}, number={1}, journal={JOURNAL OF MOLECULAR EVOLUTION}, author={Rosinski, JA and Atchley, WR}, year={1998}, month={Jan}, pages={74–83} }
 @article{atchley_fitch_1997, title={A natural classification of the basic helix-loop-helix class of transcription factors}, volume={94}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.94.10.5172}, abstractNote={A natural (evolutionary) classification is provided for 242 basic helix-loop-helix (bHLH) motif-containing proteins. Phylogenetic analyses of amino acid sequences describe the patterns of evolutionary change within the motif and delimit evolutionary lineages. These evolutionary lineages represent well known functional groups of proteins and can be further arranged into five groups based on binding to DNA at the hexanucleotide E-box, the amino acid patterns in other components of the motif, and the presence/absence of a leucine zipper. The hypothesized ancestral amino acid sequence for the bHLH transcription factor family is given together with the ancestral sequences of the subgroups. It is suggested that bHLH proteins containing a leucine zipper are not a natural, monophyletic group.}, number={10}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Atchley, WR and Fitch, WM}, year={1997}, month={May}, pages={5172–5176} }
 @article{atchley_xu_cowley_1997, title={Altering developmental trajectories in mice by restricted index selection}, volume={146}, number={2}, journal={Genetics}, author={Atchley, W. R. and Xu, S. and Cowley, D. E.}, year={1997}, pages={629–640} }
 @article{atchley_zhu_1997, title={Developmental quantitative genetics, conditional epigenetic variability and growth in mice}, volume={147}, number={2}, journal={Genetics}, author={Atchley, W. R. and Zhu, J.}, year={1997}, pages={765–776} }
 @article{atchley_xu_vogl_1994, title={DEVELOPMENTAL QUANTITATIVE GENETIC MODELS OF EVOLUTIONARY CHANGE}, volume={15}, ISSN={["0192-253X"]}, DOI={10.1002/dvg.1020150110}, abstractNote={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.}, number={1}, journal={DEVELOPMENTAL GENETICS}, author={ATCHLEY, WR and XU, SZ and VOGL, C}, year={1994}, pages={92–103} }
 @article{atchley_fitch_1993, title={Genetic affinities of inbred mouse strains of uncertain origin}, volume={10}, number={6}, journal={Molecular Biology and Evolution}, author={Atchley, W. R. and Fitch, W.}, year={1993}, pages={1150} }
 @article{atchley_logsdon_cowley_eisen_1991, title={UTERINE EFFECTS, EPIGENETICS, AND POSTNATAL SKELETAL DEVELOPMENT IN THE MOUSE}, volume={45}, ISSN={["0014-3820"]}, DOI={10.2307/2409697}, number={4}, journal={EVOLUTION}, author={ATCHLEY, WR and LOGSDON, T and COWLEY, DE and EISEN, EJ}, year={1991}, month={Jun}, pages={891–909} }
 @article{atchley_newman_1989, title={A QUANTITATIVE-GENETICS PERSPECTIVE ON MAMMALIAN DEVELOPMENT}, volume={134}, ISSN={["1537-5323"]}, DOI={10.1086/284993}, abstractNote={These discussions are intended to describe some important aspects of evolutionary change in complex traits from a developmental quantitative-genetics perspective. These comments support the contention that information about the complexity of the trait, the dynamics of the underlying controlling factors, and an age-specific response to selection must be incorporated into discussions of evolutionary change by selection. The developmental complexity of a trait strongly influences attempts to ascertain its genetic architecture and its age-specific response to selection. The component parts are often under separate genetic control, and there is a substantial nonheritable component to many of these components. Recognition of this complexity permits variability in composite traits to be decomposed; the genetic architecture of the individual subunits is thus determined, yielding a more holistic picture of the genetic structure of the entire trait. Furthermore, it is clear that these complex traits could be altered by selection operating on any or all of the component parts. The magnitude and direction of selection response in complex traits are a function of the genetic-covariance structure among the component parts. As an additional consequence, it is possible that the same end-point phenotype can be obtained by changing different combinations of the component parts. If so, the correlated response to selection in other traits can be quite varied, depending on which component of the complex trait is changed by selection and on the genetic-covariance structure among the component parts within a trait and between traits. There are significant ontogenetic aspects of the underlying causal factors-that is, direct and indirect genetic factors-that are controlling each component part of a complex trait. The course of development in a complex trait involves coordination and integration of a number of separate biological processes that begin functioning during the early ontogeny of an organism. Genes influencing expression of these processes in mammals may arise from the individual's own genome and, as a result, contribute directly to production of the phenotype. In addition, during the prenatal and preweaning phases of ontogeny, the expression of genes in the individual's mother may contribute indirectly to the developmental expression of her progeny's phenotype. The interrelationship between direct and indirect maternal genetic factors has a decided ontogenetic aspect, since they contribute differentially during the prenatal, postnatal, and postweaning phases of development. Indeed, the magnitude and the direction of the contribution of these two separate but possibly correlated sets of genetic effects may change considerably as a function of the stage of ontogeny of the organism. The result of an ontogenetically changing set of genetic controlling factors is a much more complex response to selection than is predicted by the direct-effects genetic model. The size and magnitude of the genetic correlation between direct and maternal components of variability determine the direction and the rate of evolutionary change by selection. A negative genetic covariance between direct and maternal genetic components, which is common for many complex traits, greatly complicates the estimation of genetic parameters and the prediction of evolutionary change by selection. The actual components of a complex trait that is responding to selection may be strongly affected by the developmental age at which selection occurs. However, in addition to the qualitative aspects of selection response, developmental age may also have a quantitative component because of the age-dependent contribution of maternal effects. The earlier during ontogeny that selection is focused, the greater the potential contribution of maternal effects. Because of the potential for a negative covariance between direct and maternal genetic effects, the contribution to the selection response made by maternal effects can be quite complicated.}, number={3}, journal={AMERICAN NATURALIST}, author={ATCHLEY, WR and NEWMAN, S}, year={1989}, month={Sep}, pages={486–512} }