Biomedical subjects

Jianying Gu

Publications and source records attributed to Jianying Gu.

9 recordsLinked to original sources

PubMed2007

Genome evolution and functional divergence in Yersinia.

The steadily increasing number of prokaryotic genomes has accelerated the study of genome evolution; in particular, the availability of sets of genomes from closely related bacteria has made exploration of questions surrounding the evolution of pathogenesis tractable. Here we present the results of a detailed comparison of the genomes of Yersinia pseudotuberculosis IP32593 and three strains of Yersinia pestis (CO92, KIM10, and 91001). There appear to be between 241 and 275 multigene families in these organisms. There are 2,568 genes that are identical in the three Y. pestis strains, but differ from the Y. pseudotuberculosis strain. The changes found in some of these families, such as the kinases, proteases, and transporters, are illustrative of how the evolutionary jump from the free-living enteropathogen Y. pseudotuberculosis to the obligate host-borne blood pathogen Y. pestis was achieved. We discuss the composition of some of the most important families and discuss the observed divergence between Y. pseudotuberculosis and Y. pestis homologs.

Base Sequence↗

PubMed2006

Are GC-rich isochores vanishing in mammals?

Several studies of nucleotide substitution patterns in mammalian species suggested that GC-rich isochores might be vanishing in mammalian genomes. However, the number of genes and the number of genomes included in these studies might not have given a reliable broad view of the trend in GC change in mammals. It is therefore worth exploiting this issue with a broader coverage of mammalian genomes using a reliable approach, the maximum likelihood approach. We have applied two maximum likelihood methods to infer the ancestral GC contents of 176 mammalian genes from representative eutherian species and at least one marsupial species. Except for a large GC decrease in marsupial genes, we found no general decreasing trend in GC content in GC-rich genes or in other genes among eutherian mammals; indeed, the GC content of GC-rich genes appears to have increased in recent times in some genomes, e.g., the rabbit. For the large GC decrease in marsupials, it could be mainly due to the great reduction in chromosome number, which could lead to a large reduction in recombination rate and thus also a large reduction in the rate of gene conversion. Since many eutherian mammals still maintain a fairly large number of chromosomes, it is unlikely that GC-rich isochores are vanishing in these mammals.

Animals↗

PubMed2004

Ordered origin of the typical two- and three-repeat Myb genes.

Myb domain proteins contain a conserved DNA-binding domain composed of one to four conserved repeat motifs. In animals, Myb proteins are encoded by a small gene family and commonly contain three repeat motifs (R1R2R3); whereas, plant Myb proteins are encoded by a very large and diverse gene family in which a motif containing two repeats (R2R3) is the most common. In contrast to the conservation in the Myb domain, other regions of Myb proteins are highly variable. To explore the evolutionary origin of Myb genes, we cloned and sequenced Myb domains from maize and sorghum, and conducted a comprehensive phylogenetic analysis of Myb genes. The results indicate that the origins of individual Myb repeats are strikingly distinct, and that the R2 repeat has evolved more slowly than the R1 and R3 repeats. However, it is not clear which repeat is the most ancient one. The evidence also suggests that R2R3 and R1R2R3 Myb genes co-existed in eukaryotes before the divergence of plants and animals. Based on our results, we propose that R1R2R3 Myb genes were derived from R2R3 Myb genes by gain of the R1 repeat through an ancient intragenic duplication; this gain model is more parsimonious than the previous proposal that R2R3 Myb genes were derived from R1R2R3 Mybs by loss of the R1 repeat. A separate group of diverse non-typical Myb proteins exhibits a polyphyletic origin and a complex evolutionary pattern. Finally, a small group of ancient Myb paralogs prior to the amplification of current Myb genes is identified. Together, these results support a new model for the ordered evolution of Myb gene family.

Binding Sites↗

PubMed2004

How much expression divergence after yeast gene duplication could be explained by regulatory motif evolution?

We used the yeast genome sequences of gene families, microarray profiles and regulatory motif data to test the current wisdom that there is a strong correlation between regulatory motif structure and gene expression profile. Our results suggest that duplicate genes tend to be co-expressed but the correlation between motif content and expression similarity is generally poor, only approximately 2-3% of expression variation can be explained by the motif divergence. Our observations suggest that, in addition to the cis-regulatory motif structure in the upstream region of the gene, multiple trans-acting factors in the gene network can influence the pattern of gene expression significantly.

Evolution, Molecular↗

PubMed2004

Further statistical analysis for genome-wide expression evolution in primate brain/liver/fibroblast tissues.

In spite of only a 1-2 per cent genomic DNA sequence difference, humans and chimpanzees differ considerably in behaviour and cognition. Affymetrix microarray technology provides a novel approach to addressing a long-term debate on whether the difference between humans and chimpanzees results from the alteration of gene expressions. Here, we used several statistical methods (distance method, two-sample t-tests, regularised t-tests, ANOVA and bootstrapping) to detect the differential expression pattern between humans and great apes. Our analysis shows that the pattern we observed before is robust against various statistical methods; that is, the pronounced expression changes occurred on the human lineage after the split from chimpanzees, and that the dramatic brain expression alterations in humans may be mainly driven by a set of genes with increased expression (up-regulated) rather than decreased expression (down-regulated).

Animals↗

PubMed2003

Natural history and functional divergence of protein tyrosine kinases.

Cellular signaling is important for many biological processes including growth, differentiation, adhesion, motility and apoptosis. The protein tyrosine kinase (PTK) supergene family is the key mediator in cellular signaling in metazoans, directly associated with a variety of human diseases. All PTKs contain a highly conserved catalytic kinase domain, in spite of variable multi-domain structures. Within each PTK gene family, members exhibit functional divergence in substrate-specificity or temporal/tissue-specific expression, although their primary function is conserved. After conducting phylogenetic analysis on major PTK gene families, we found that the expanding of each PTK family was likely caused by gene or genome duplication event(s) that occurred before the emergence of teleosts but after the vertebrate-amphioxus split. We further investigated the evolutionary pattern of functional divergence after gene duplication in those gene families. Our results show that site-specific shifted evolutionary rate (altered functional constraint) is a common pattern in PTK gene family evolution.

Animals↗

PubMed2003

Induced gene expression in human brain after the split from chimpanzee.

Despite only approximately 1% difference in genomic DNA sequence, humans and chimpanzees differ considerably in mental and linguistic capabilities, and in susceptibility to some diseases. A recent comparison of gene expression in human and great apes cast some light on the genetic basis of these differences, but more rigorous study is required. Our statistical reanalysis of these microarray data shows that there have indeed been dramatic alterations in the expression of genes in the human brain since the split from chimpanzees, mainly caused by a set of genes with increased (rather than decreased) expression in the human brain.

Animals↗

PubMed2002

Age distribution of human gene families shows significant roles of both large- and small-scale duplications in vertebrate evolution.

The classical (two-round) hypothesis of vertebrate genome duplication proposes two successive whole-genome duplication(s) (polyploidizations) predating the origin of fishes, a view now being seriously challenged. As the debate largely concerns the relative merits of the 'big-bang mode' theory (large-scale duplication) and the 'continuous mode' theory (constant creation by small-scale duplications), we tested whether a significant proportion of paralogous genes in the contemporary human genome was indeed generated in the early stage of vertebrate evolution. After an extensive search of major databases, we dated 1,739 gene duplication events from the phylogenetic analysis of 749 vertebrate gene families. We found a pattern characterized by two waves (I, II) and an ancient component. Wave I represents a recent gene family expansion by tandem or segmental duplications, whereas wave II, a rapid paralogous gene increase in the early stage of vertebrate evolution, supports the idea of genome duplication(s) (the big-bang mode). Further analysis indicated that large- and small-scale gene duplications both make a significant contribution during the early stage of vertebrate evolution to build the current hierarchy of the human proteome.

Animals↗

PubMed2002

Evolutionary analysis for functional divergence of Jak protein kinase domains and tissue-specific genes.

Jak (Janus kinase) is a nonreceptor tyrosine kinase, which plays important roles in signal transduction pathways. The unique feature of Jak is that, in addition to a fully functional tyrosine kinase domain (JH1), Jak possesses a pseudokinase domain (JH2). Although JH2 lost its catalytic function, experimental evidence has shown that this domain may have acquired some new but unknown functions. This apparent functional divergence after the (internal) domain duplication may result in dramatic changes of selective constraints at some sites. We conducted a data analysis to test this hypothesis. Our result shows that shifted selective constraints (or shifted evolutionary rates) between the JH1 and the JH2 domains are statistically significant. Predicted amino acid sites by posterior analysis can be classified into two groups: very conserved in JH1 but highly variable in JH2, and vice versa. Moreover, we have studied the evolutionary pattern of four tissue-specific genes, Jak1, Jak2, Jak3, and Tyk2, which were generated in the early stages of vertebrates. We found that after the (first) gene duplication, site-specific rate shifts between Jak2/Jak3 and Jak1/Tyk are significant, presumably as a consequence of functional divergence among these genes. The implication of our study for functional genomics is discussed.

Amino Acids↗