Biomedical subjects

Zhenglong Gu

Publications and source records attributed to Zhenglong Gu.

13 recordsLinked to original sources

PubMed2007

Rapid evolution in a pair of recent duplicate segments of rice.

Gene duplication has been considered the most important way of generating genetic novelties. The subsequent evolution right after gene duplication is critical for new function to occur. Here we analyzed the evolutionary pattern for a recently duplicated segment between rice chromosomes 11 and 12. This duplication event was estimated to occur about 6 million years ago, during the divergence of the B- and C-genome rice species. The duplicate segment in chromosome 12 has significantly higher frequency of sequence rearrangement rate than non-duplicated regions. The rearrangement rate is approximately 6.5 breakages/Mb per million years, about six times higher than the fastest rate ever reported in eukaryotes. The genes within both segments experienced accelerated nucleotide substitution rates revealed by synonymous (Ks) and non-synonymous divergence (Ka) between Oryza sativa indica and O. sativa japonica. Analysis using EST data also implicates rapid divergence in expression between these segmental duplicate genes. These overall rapid changes from different perspective for the first time provide evidence that relaxation of selection also occurs in large-scale duplications.

Base Sequence↗

PubMed2005

Elevated evolutionary rates in the laboratory strain of Saccharomyces cerevisiae.

By using the maximum likelihood method, we made a genome-wide comparison of the evolutionary rates in the lineages leading to the laboratory strain (S288c) and a wild strain (YJM789) of Saccharomyces cerevisiae and found that genes in the laboratory strain tend to evolve faster than in the wild strain. The pattern of elevated evolution suggests that relaxation of selection intensity is the dominant underlying reason, which is consistent with recurrent bottlenecks in the S. cerevisiae laboratory strain population. Supporting this conclusion are the following observations: (i) the increases in nonsynonymous evolutionary rate occur for genes in all functional categories; (ii) most of the synonymous evolutionary rate increases in S288c occur in genes with strong codon usage bias; (iii) genes under stronger negative selection have a larger increase in nonsynonymous evolutionary rate; and (iv) more genes with adaptive evolution were detected in the laboratory strain, but they do not account for the majority of the increased evolution. The present discoveries suggest that experimental and possible industrial manipulations of the laboratory strain of yeast could have had a strong effect on the genetic makeup of this model organism. Furthermore, they imply an evolution of laboratory model organisms away from their wild counterparts, questioning the relevancy of the models especially when extensive laboratory cultivation has occurred. In addition, these results shed light on the evolution of livestock and crop species that have been under human domestication for years.

Biological Evolution↗

PubMed2005

Molecular mechanisms involved in robustness of yeast central metabolism against null mutations.

Adaptive strategies employed by the yeast Saccharomyces cerevisiae provide robustness and adaptability of its central metabolism. Since central metabolism in yeast has been well studied at the enzymatic and genetic levels, it represents an excellent system for evaluating the relative roles of duplicate genes and alternative metabolic pathways as possible mechanisms for the stability of central metabolism against null mutations. Yeast appears to employ a variety of mechanisms to ensure functional robustness of its central metabolism. Uninterrupted flow of energy and precursor metabolites through the pathways of central metabolism via glycolysis (EMP), pentose phosphate shunt (PPS), and the tricarboxylic acid (TCA) cycle are ensured by a variety of adaptive mechanisms. One of the most significant mechanisms appears to be gene duplication events that have produced a number of isozymes functioning under variable environmental and physiological conditions. Alternative pathways represent another important mechanism for increasing the robustness of the system. The robustness of the pathways of central metabolism is apparently higher than that of the other parts of metabolism, because of its exceptional importance to the organism's vitality. The proportion of duplicated viable genes also is substantially larger in central metabolism than that in a pool of other metabolic genes.

Citric Acid Cycle↗

PubMed2004

Comparative methods for the analysis of gene-expression evolution: an example using yeast functional genomic data.

Understanding the evolution of gene function is a primary challenge of modern evolutionary biology. Despite an expanding database from genomic and developmental studies, we are lacking quantitative methods for analyzing the evolution of some important measures of gene function, such as gene-expression patterns. Here, we introduce phylogenetic comparative methods to compare different models of gene-expression evolution in a maximum-likelihood framework. We find that expression of duplicated genes has evolved according to a nonphylogenetic model, where closely related genes are no more likely than more distantly related genes to share common expression patterns. These results are consistent with previous studies that found rapid evolution of gene expression during the history of yeast. The comparative methods presented here are general enough to test a wide range of evolutionary hypotheses using genomic-scale data from any organism.

Evolution, Molecular↗

PubMed2004

Duplicate genes increase gene expression diversity within and between species.

Using microarray gene expression data from several Drosophila species and strains, we show that duplicated genes, compared with single-copy genes, significantly increase gene expression diversity during development. We show further that duplicate genes tend to cause expression divergences between Drosophila species (or strains) to evolve faster than do single-copy genes. This conclusion is also supported by data from different yeast strains.

Animals↗

PubMed2004

Higher gene duplicabilities for metabolic proteins than for nonmetabolic proteins in yeast and E. coli.

Although the evolutionary significance of gene duplication has long been appreciated, it remains unclear what factors determine gene duplicability. In this study we investigated whether metabolism is an important determinant of gene duplicability because cellular metabolism is crucial for the survival and reproduction of an organism. Using genomic data and metabolic pathway data from the yeast (Saccharomyces cerevisiae) and Escherichia coli, we found that metabolic proteins indeed tend to have higher gene duplicability than nonmetabolic proteins. Moreover, a detailed analysis of metabolic pathways in these two organisms revealed that genes in the central metabolic pathways and the catabolic pathways have, on average, higher gene duplicability than do other genes and that most genes in anabolic pathways are single-copy genes.

Computational Biology↗

PubMed2003

Different evolutionary patterns between young duplicate genes in the human genome.

BACKGROUND: Following gene duplication, two duplicate genes may experience relaxed functional constraints or acquire different mutations, and may also diverge in function. Whether the two copies will evolve in different patterns remains unclear, however, because previous studies have reached conflicting conclusions. In order to resolve this issue, by providing a general picture, we studied 250 independent pairs of young duplicate genes from the whole human genome. RESULTS: We showed that nearly 60% of the young duplicate gene pairs have evolved at the amino-acid level at significantly different rates from each other. More than 25% of these gene pairs also showed significantly different ratios of nonsynonymous to synonymous rates (Ka/Ks ratios). Moreover, duplicate pairs with different rates of amino-acid substitution also tend to differ in the Ka/Ks ratio, with the fast-evolving copy tending to have a slightly higher Ks than the slow-evolving one. Lastly, a substantial portion of fast-evolving copies have accumulated amino-acid substitutions evenly across the protein sequences, whereas most of the slow-evolving copies exhibit uneven substitution patterns. CONCLUSIONS: Our results suggest that duplicate genes tend to evolve in different patterns following the duplication event. One copy evolves faster than the other and accumulates amino-acid substitutions evenly across the sequence, whereas the other copy evolves more slowly and accumulates amino-acid substitutions unevenly across the sequence. Such different evolutionary patterns may be largely due to different functional constraints on the two copies.

Amino Acid Substitution↗

PubMed2003

Rate of protein evolution versus fitness effect of gene deletion.

Whether nonessential genes evolve faster than essential genes has been a controversial issue. To resolve this issue, we use the data from a nearly complete set of single-gene deletions in the yeast Saccharomyces cerevisiae to assess protein dispensability. Also, instead of the nematode, which was used previously but is only distantly related to S. cerevisiae, we use another yeast, Candida albicans, as a second species to estimate the evolutionary distances between orthologous genes in two species. Our analysis reveals only a weak correlation between protein dispensability and evolutionary rate. More important, the correlation disappears when duplicate genes are removed from the analysis. And surprisingly, the average rate of nonsynonymous substitution is considerably lower than that for single-copy genes in the yeast genome. This observation suggests that structural constraints are more important in determining the rate of evolution of a protein than dispensability because duplicate genes are on average more dispensable than single-copy genes. For duplicate genes, those with only a weak effect or no effect of deletion on fitness evolve on average faster than those with a moderate or strong effect of deletion on fitness, which in turn evolve on average faster than those with a lethal effect of deletion.

Candida albicans↗

PubMed2003

Role of duplicate genes in genetic robustness against null mutations.

Deleting a gene in an organism often has little phenotypic effect, owing to two mechanisms of compensation. The first is the existence of duplicate genes: that is, the loss of function in one copy can be compensated by the other copy or copies. The second mechanism of compensation stems from alternative metabolic pathways, regulatory networks, and so on. The relative importance of the two mechanisms has not been investigated except for a limited study, which suggested that the role of duplicate genes in compensation is negligible. The availability of fitness data for a nearly complete set of single-gene-deletion mutants of the Saccharomyces cerevisiae genome has enabled us to carry out a genome-wide evaluation of the role of duplicate genes in genetic robustness against null mutations. Here we show that there is a significantly higher probability of functional compensation for a duplicate gene than for a singleton, a high correlation between the frequency of compensation and the sequence similarity of two duplicates, and a higher probability of a severe fitness effect when the duplicate copy that is more highly expressed is deleted. We estimate that in S. cerevisiae at least a quarter of those gene deletions that have no phenotype are compensated by duplicate genes.

Evolution, Molecular↗

PubMed2003

Patterns of gene duplication in Saccharomyces cerevisiae and Caenorhabditis elegans.

In this paper we present a new method for detecting block duplications in a genome. It is more stringent than previous ones in that it requires a more rigorous definition of paralogous genes and that it requires the paralogous proteins on the two blocks to be contiguous. In addition, it provides three criterion choices: (1) the same composition (i.e., having the same paralogues in the two windows), (2) the same composition and gene order, and (3) the same composition, gene order, and gene orientation. The method is completely automated, requiring no visual inspection as in previous methods. We applied it to analyze the complete genomes of S. cerevisiae and C. elegans. In yeast we detected fewer duplicated blocks than previously reported. In C. elegans, however, we detected more block duplications than previously reported, indicating that although our method has a more stringent definition of block duplication than previous ones, it may be more sensitive in detection because it considers every possible window rather than only fixed nonoverlapping windows. Our results show that block duplication is a common phenomenon in both organisms. The patterns of block duplication in the two species are, however, markedly different. The yeast shows much more extensive block duplication than the nematode, with some chromosomes having more than 40% of the duplications derived from block duplications. Moreover, in the yeast the majority of block duplications occurred between chromosomes, while in the nematode most block duplications occurred within chromosomes.

Animals↗

PubMed2003

Detection of gene duplications and block duplications in eukaryotic genomes.

Several eukaryotic genomes have been completely sequenced and this provides an opportunity to investigate the extent and characteristics (e.g., single gene duplication, block duplication, etc.) of gene duplication in a genome. Detecting duplicate genes in a genome, however, is not a simple problem because of several complications such as domain shuffling, the existence of isoforms derived from alternative splicing, and annotational errors in the databases. We describe a method for overcoming these difficulties and the extents of gene duplication in the genomes of Drosophila melanogaster, Caenorhabditis elegans, and yeast inferred from this method. We also describe a method for detecting block duplications in a genome. Application of this method showed that block duplication is a common phenomenon in both yeast and nematode. The patterns of block duplication in the two species are, however, markedly different. Yeast shows much more extensive block duplication than nematode, with some chromosomes having more than 40% of the duplications derived from block duplications. Moreover, in yeast the majority of block duplications occurred between chromosomes, while in nematode most block duplications occurred within chromosomes.

Animals↗

PubMed2002

Rapid divergence in expression between duplicate genes inferred from microarray data.

For more than 30 years, expression divergence has been considered as a major reason for retaining duplicated genes in a genome, but how often and how fast duplicate genes diverge in expression has not been studied at the genomic level. Using yeast microarray data, we show that expression divergence between duplicate genes is significantly correlated with their synonymous divergence (K(S)) and also with their nonsynonymous divergence (K(A)) if K(A) </= 0.3. Thus, expression divergence increases with evolutionary time, and K(A) is initially coupled with expression divergence. More interestingly, a large proportion of duplicate genes have diverged quickly in expression and the vast majority of gene pairs eventually become divergent in expression. Indeed, more than 40% of gene pairs show expression divergence even when K(S) is </= 0.10, and this proportion becomes >80% for K(S) > 1.5. Only a small fraction of ancient gene pairs do not show expression divergence.

Evolution, Molecular↗

PubMed2002

Extent of gene duplication in the genomes of Drosophila, nematode, and yeast.

We conducted a detailed analysis of duplicate genes in three complete genomes: yeast, Drosophila, and Caenorhabditis elegans. For two proteins belonging to the same family we used the criteria: (1) their similarity is > or =I (I = 30% if L > or = 150 a.a. and I = 0.01n + 4.8L(-0.32(1 + exp(-L/1000))) if L < 150 a.a., where n = 6 and L is the length of the alignable region), and (2) the length of the alignable region between the two sequences is > or = 80% of the longer protein. We found it very important to delete isoforms (caused by alternative splicing), same genes with different names, and proteins derived from repetitive elements. We estimated that there were 530, 674, and 1,219 protein families in yeast, Drosophila, and C. elegans, respectively, so, as expected, yeast has the smallest number of duplicate genes. However, for the duplicate pairs with the number of substitutions per synonymous site (K(S)) < 0.01, Drosophila has only seven pairs, whereas yeast has 58 pairs and nematode has 153 pairs. After considering the possible effects of codon usage bias and gene conversion, these numbers became 6, 55, and 147, respectively. Thus, Drosophila appears to have much fewer young duplicate genes than do yeast and nematode. The larger numbers of duplicate pairs with K(S) < 0.01 in yeast and C. elegans were probably largely caused by block duplications. At any rate, it is clear that the genome of Drosophila melanogaster has undergone few gene duplications in the recent past and has much fewer gene families than C. elegans.

Animals↗