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Kevin Thornton

Publications and source records attributed to Kevin Thornton.

14 recordsLinked to original sources
PubMed2006

X chromosomes and autosomes evolve at similar rates in Drosophila: no evidence for faster-X protein evolution.

Recent data from Drosophila suggest that a substantial fraction of amino acid substitutions observed between species are beneficial. If these beneficial mutations are on average partially recessive, then the rate of protein evolution is predicted to be faster for X-linked genes compared to autosomal genes (the "faster-X" hypothesis). We test this prediction by comparing rates of protein substitutions between orthologous genes, taking advantage of variations in chromosome fusions within the genus Drosophila. In members of the Drosophila melanogaster species group, the chromosomal arm 3L segregates as an ordinary autosome (i.e., two homologous copies in both males and females). However, in the Drosophila pseudoobscura species group, this chromosomal arm has become fused to the ancestral X chromosome and is hemizygous in males. The faster-X hypothesis predicts that protein evolution should be faster for genes on this chromosomal arm in the D. pseudoobscura lineage, relative to the D. melanogaster lineage. Here we combine new sequence data for 202 gene fragments in Drosophila miranda (in the pseudoobscura species group) with the completed genomes of D. melanogaster, D. pseudoobscura, and Drosophila yakuba to show that there are no detectable differences in rates of amino acid evolution for orthologous X-linked and autosomal genes. Our results imply that the contribution of the faster-X (if any) to the large-X effect on reproductive isolation in Drosophila is not due to a generally faster rate of protein evolution. The lack of a detectable faster-X effect in these species suggests either that beneficial amino acids are not partially recessive on average, or that adaptive evolution does not often use newly arising amino acid mutations.

Amino Acid Substitution↗
PubMed2006

Kinetic analysis of a high-affinity antibody/antigen interaction performed by multiple Biacore users.

To explore the reliability of Biacore-based assays, 22 study participants measured the binding of prostate-specific antigen (PSA) to a monoclonal antibody (mAb). Each participant was provided with the same reagents and a detailed experimental protocol. The mAb was immobilized on the sensor chip at three different densities and a two-step assay was used to determine the kinetic and affinity parameters of the PSA/mAb complex. First, PSA was tested over a concentration range of 2.5-600 nM to obtain k(a) information. Second, to define the k(d) of this stable antigen/antibody complex accurately, the highest PSA concentration was retested with the dissociation phase of each binding cycle monitored for 1h. All participants collected data that could be analyzed to obtain kinetic parameters for the interaction. The association and the extended-dissociation data derived from the three antibody surfaces were globally fit using a simple 1:1 interaction model. The average k(a) and k(d) for the PSA/mAb interaction as calculated from the 22 analyses were (4.1+/-0.6) x 10(4) M(-1) s(-1) and (4.5+/-0.6) x 10(-5) s(-1), respectively. Overall, the experimental standard errors in the rate constants were only approximately 14%. Based on the kinetic rate constants, the affinity (K(D)) of the PSA/mAb interaction was 1.1+/-0.2 nM.

Antibodies, Monoclonal↗
PubMed2006

Extensive introgression of mitochondrial DNA relative to nuclear genes in the Drosophila yakuba species group.

Studies of gene flow between recently diverged species can illuminate the role of natural selection in the formation of new species. Drosophila santomea and D. yakuba are recently diverged, partially reproductively isolated species that continue to hybridize in the wild, and appear to be reproductively isolated from the more distantly related species D. teissieri. We examine patterns of nucleotide polymorphism and divergence in these three species at multiple X-linked, Y-linked, and mitochondrial markers. All three species harbor drastically reduced variability on the Y chromosome relative to the X, as expected for a nonrecombining chromosome subject to variation-reducing selection. The three species are generally well differentiated at the nuclear markers, with little evidence for recent introgression for either the X- or Y-linked genes. Based on the nuclear genes, we estimate that D. santomea and D. yakuba diverged about one-half million years ago and split from D. teissieri about one million years ago. In contrast to the pattern at nuclear loci, all three species share a very similar mtDNA haplotype. We show that the mtDNA must have recently introgressed across species boundaries in the D. yakuba subgroup and that its fixation was driven by either selection on the mitochondria itself or other cytoplasmic factors. These results demonstrate that different regions of the genome can have distinct evolutionary dynamics in the context of species formation. Although natural selection is usually thought of as accentuating divergence between species, our results imply that it can also act as a homogenizing force.

Animals↗
PubMed2005

Identification by full-coverage array CGH of human DNA copy number increases relative to chimpanzee and gorilla.

Duplication of chromosomal segments and associated genes is thought to be a primary mechanism for generating evolutionary novelty. By comparative genome hybridization using a full-coverage (tiling) human BAC array with 79-kb resolution, we have identified 63 chromosomal segments, ranging in size from 0.65 to 1.3 Mb, that have inferred copy number increases in human relative to chimpanzee. These segments span 192 Ensembl genes, including 82 gene duplicates (41 reciprocal best BLAST matches). Synonymous and nonsynonymous substitution rates across these pairs provide evidence for general conservation of the amino acid sequence, consistent with the maintenance of function of both copies, and one case of putative positive selection for an uncharacterized gene. Surprisingly, the core histone genes H2A, H2B, H3, and H4 have been duplicated in the human lineage since our split with chimpanzee. The observation of increased copy number of a human cluster of core histone genes suggests that altered dosage, even of highly constrained genes, may be an important evolutionary mechanism.

Animals↗
PubMed2005

Approximate Bayesian inference reveals evidence for a recent, severe bottleneck in a Netherlands population of Drosophila melanogaster.

Genome-wide nucleotide variation in non-African populations of Drosophila melanogaster is a subset of variation found in East sub-Saharan African populations, suggesting a bottleneck in the history of the former. We implement an approximate Bayesian approach to infer the timing, duration, and severity of this putative bottleneck and ask whether this inferred model is sufficient to account for patterns of variability observed at 115 loci scattered across the X chromosome. We estimate a recent bottleneck 0.006N(e) generations ago, somewhat further in the past than suggested by biogeographical evidence. Using various proposed statistical tests, we find that this bottleneck model is able to predict the majority of observed features of diversity and linkage disequilibrium in the data. Thus, while precise estimates of bottleneck parameters (like inferences of selection) are sensitive to model assumptions, our results imply that it may be unnecessary to invoke frequent selective sweeps associated with the dispersal of D. melanogaster from Africa to explain patterns of variability in non-African populations.

Animals↗
PubMed2005

Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution.

We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each arm gene order has been extensively reshuffled, leading to a minimum of 921 syntenic blocks shared between the species. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 25-55 million years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences between the species--but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila.

Animals↗
PubMed2004

Excess of amino acid substitutions relative to polymorphism between X-linked duplications in Drosophila melanogaster.

We have obtained sequence polymorphism data from 13 genes belonging to 5 gene families in Drosophila melanogaster where the K(a)/K(s) between copies is greater than 1. Twelve of these 13 loci are X-linked. In general, there is evidence of purifying selection in all families, as inferred both from levels of silent and replacement variation and insertion/deletion variation, suggesting that the loci are likely functional. Shared polymorphisms indicative of gene conversion between paralogs are rare among the X-linked families, in contrast to available data from autosomal duplicates. McDonald-Kreitman tests between duplicates reveal an excess of amino-acid fixations between copies in the X-linked families, suggesting that the divergence between these loci was driven by positive selection. In contrast, available data from autosomal duplicates show a deficit of fixations, consistent with gene conversion being a strong homogenizing force.

Amino Acid Substitution↗
PubMed2004

Nucleotide variation and recombination along the fourth chromosome in Drosophila simulans.

The fourth chromosome of Drosophila melanogaster and its sister species are believed to be nonrecombining and have been a model system for testing predictions of the effects of selection on linked, neutral variation. We recently examined nucleotide variation along the chromosome of D. melanogaster and revealed that a low average level of recombination could be associated with considerably high levels of nucleotide variation. In this report, we further investigate the variation along the fourth chromosome of D. simulans. We sequenced 12 gene regions evenly distributed along the fourth chromosome for a worldwide collection of 11 isofemale lines and 5 gene regions in a local population of 10 isofemale lines from South America. In contrast to predictions for regions of very low recombination, these data reveal that the variation levels in many gene regions, including an intron region of the ci gene, vary considerably along the fourth chromosome. Nucleotide diversity ranged from 0.0010 to 0.0074 in 9 gene regions interspersed with several regions of greatly reduced variation. Tests of recombination indicate that the recombination level is not as low as previously thought, likely an order of magnitude higher than that in D. melanogaster. Finally, estimates of the recombination parameters are shown to support a crossover-plus-conversion model.

Animals↗
PubMed2003

Libsequence: a C++ class library for evolutionary genetic analysis.

UNLABELLED: A C++ class library is available to facilitate the implementation of software for genomics and sequence polymorphism analysis. The library implements methods for data manipulation and the calculation of several statistics commonly used to analyze SNP data. The object-oriented design of the library is intended to be extensible, allowing users to design custom classes for their own needs. In addition, routines are provided to process samples generated by a widely used coalescent simulation. AVAILABILITY: The source code (in C++) is available from http://www.molpopgen.org

Algorithms↗
PubMed2003

The origin of new genes: glimpses from the young and old.

Genome data have revealed great variation in the numbers of genes in different organisms, which indicates that there is a fundamental process of genome evolution: the origin of new genes. However, there has been little opportunity to explore how genes with new functions originate and evolve. The study of ancient genes has highlighted the antiquity and general importance of some mechanisms of gene origination, and recent observations of young genes at early stages in their evolution have unveiled unexpected molecular and evolutionary processes.

Animals↗
PubMed2002

Nucleotide variation along the Drosophila melanogaster fourth chromosome.

The Drosophila melanogaster fourth chromosome, believed to be nonrecombining and invariable, is a classic example of the effect of natural selection in eliminating genetic variation in linked loci. However, in a chromosome-wide assay of nucleotide variation in natural populations, we have observed a high level of polymorphism in a approximately 200-kilobase region and marked levels of polymorphism in several other fragments interspersed with regions of little variation, suggesting different evolutionary histories in different chromosomal domains. Statistical tests of neutral evolution showed that a few haplotypes predominate in the 200-kilobase polymorphic region. Finally, contrary to the expectation of no recombination, we identified six recombination events within the chromosome. Thus, positive Darwinian selection and recombination have affected the evolution of this chromosome.

Animals↗
PubMed2002

Rapid divergence of gene duplicates on the Drosophila melanogaster X chromosome.

The recent sequencing of several eukaryotic genomes has generated considerable interest in the study of gene duplication events. The classical model of duplicate gene evolution is that recurrent mutation ultimately results in one copy becoming a pseudogene, and only rarely will a beneficial new function evolve. Here, we study divergence between coding sequence duplications in Drosophila melanogaster as a function of the linkage relationship between paralogs. The mean K(a)/K(s) between all duplicates in the D. melanogaster genome is 0.2803, indicating that purifying selection is maintaining the structure of duplicate coding sequences. However, the mean K(a)/K(s) between duplicates that are both on the X chromosome is 0.4701, significantly higher than the genome average. Further, the distribution of K(a)/K(s) for these X-linked duplicates is significantly shifted toward higher values when compared with the distributions for paralogs in other linkage relationships. Two models of molecular evolution provide qualitative explanations of these observations-relaxation of selective pressure on the duplicate copies and, more likely, positive selection on recessive adaptations. We also show that there is an excess of X-linked duplicates with low K(s), suggesting a larger proportion of relatively young duplicates on the D. melanogaster X chromosome relative to autosomes.

Animals↗
PubMed2002

Retroposed new genes out of the X in Drosophila.

New genes that originated by various molecular mechanisms are an essential component in understanding the evolution of genetic systems. We investigated the pattern of origin of the genes created by retroposition in Drosophila. We surveyed the whole Drosophila melanogaster genome for such new retrogenes and experimentally analyzed their functionality and evolutionary process. These retrogenes, functional as revealed by the analysis of expression, substitution, and population genetics, show a surprisingly asymmetric pattern in their origin. There is a significant excess of retrogenes that originate from the X chromosome and retropose to autosomes; new genes retroposed from autosomes are scarce. Further, we found that most of these X-derived autosomal retrogenes had evolved a testis expression pattern. These observations may be explained by natural selection favoring those new retrogenes that moved to autosomes and avoided the spermatogenesis X inactivation, and suggest the important role of genome position for the origin of new genes.

Animals↗