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Chung-I Wu

Publications and source records attributed to Chung-I Wu.

At least 19 recordsLinked to original sources
PubMed2006

The accumulation of deleterious mutations in rice genomes: a hypothesis on the cost of domestication.

The extent of molecular differentiation between domesticated animals or plants and their wild relatives is postulated to be small. The availability of the complete genome sequences of two subspecies of the Asian rice, Oryza sativa (indica and japonica) and their wild relatives have provided an unprecedented opportunity to study divergence following domestication. We observed significantly more amino acid substitutions during rice domestication than can be expected from a comparison among wild species. This excess is disproportionately larger for the more radical kinds of amino acid changes (e.g. Cys<-->Tyr). We estimate that approximately a quarter of the amino acid differences between rice cultivars are deleterious, not accountable by the relaxation of selective constraints. This excess is negatively correlated with the rate of recombination, suggesting that 'hitchhiking' has occurred. We hypothesize that during domestication artificial selection increased the frequency of many deleterious mutations.

Crops, Agricultural↗
PubMed2006

An ancient balanced polymorphism in a regulatory region of human major histocompatibility complex is retained in Chinese minorities but lost worldwide.

The coding regions of many of the major histocompatibility complex (MHC) (human leukocyte antigen [HLA] in humans) molecules are believed to be subject to balancing selection. But it is less certain whether the regulatory regions of such coding sequences are also subject to the same type of selection. Here, we studied the polymorphism of the regulatory regions of the HLA-DPA1 and HLA-DPB1 genes among ethnic minorities in southwestern China. Phylogenetic analysis revealed two deep clades >10 million years old. There is almost complete linkage disequilibrium between the regulatory and coding regions of HLA-DPA1, which hints at coadaptive balancing selection on the entire region. Thus, the molecular mechanism of balancing selection in MHC may involve expression modulation in addition to coding-region polymorphisms. Although the frequency of clade II is >30% in some ethnic minorities, it decreases to <5% among southern Han Chinese and vanishes among Europeans. As suspected, some ancient balanced polymorphisms, lost in major populations, still exist in isolated ethnicities. These isolated populations may thus contribute disproportionately to the total diversity of modern humans.

Amino Acid Sequence↗
PubMed2006

Proper control of genetic background with precise allele substitution: a comment on Coyne and Elwyn.

Coyne and Elwyn report that, using Drosophila stocks provided by us, they were unable to replicate our experiments measuring the effects of desaturase-2 on stress tolerance. In this note, we provide evidence that these authors did not properly control for the differences in genetic background between the lines. Their experiments are thus not meaningful replications of our previous ones. We discuss ways of circumventing this problem in studies involving induced mutations in single genes.

Animals↗
PubMed2005

Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Molecular genetics of natural populations.

Significant progress in evolutionary genetics has been made by studying, on the one hand, patterns of DNA sequence polymorphism and, on the other, genetic architecture of complex adaptive traits. However, connections between nucleotide variants under selection and adaptively relevant phenotypes are missing. Such connections can be established using precise gene replacement. We review the recent successful introduction of this technique to the analysis of two evolutionarily interesting loci--Odysseus and desaturase2. Both genes have subtle phenotypes that nevertheless could be identified using gene replacement, demonstrating that effects of naturally occurring alleles can be measured in the laboratory. This is an important first step in connecting statistical signatures of selection with adaptation in nature. More candidate genes involved in adaptation, for example, through cloning of genes responsible for reproductive isolation, now need to be identified. Molecular genetic manipulation, DNA polymorphism analysis, and field studies then have to be integrated to provide fresh insights into the mechanisms of evolutionary change.

Alleles↗
PubMed2005

Adaptive loss of an old duplicated gene during incipient speciation.

To probe the role of natural selection in species origin, we performed a DNA polymorphism survey of the Drosophila melanogaster desaturase2 (ds2) locus. ds2 is responsible for a cuticular hydrocarbon difference between two behaviorally isolated races--Zimbabwe (Z) and Cosmopolitan (M). The ds2 allele prevalent in the Z populations is functional, while the allele from the M populations harbors a 16-bp deletion upstream of the gene which knocks out its expression. We find a signature of positive selection in the ds2 promoter, but not in the control gene, sas. This signature appears to be confined to the derived M population. We also find that the selection has been recent because the gene retains a signature of a selective sweep evidenced by the departure of Fay and Wu's H test from neutral expectation. We also find that ds2, as well as its duplicate pair ds1, has been maintained in the Drosophila genus for at least 40 Myr without any sign of adaptive change. Taken together with previous molecular genetic evidence, our results suggest that ds2 is one of the genes responsible for adaptive divergence of the Z and M races of D. melanogaster.

Animals↗
PubMed2005

A new method for estimating nonsynonymous substitutions and its applications to detecting positive selection.

The standard methods for computing the number of nonsynonymous substitutions (Ka) lump all amino acid changes into one single class, even though their rates of substitution vary by at least 10-fold (Tang et al., 2004). Classifying these changes by their physicochemical properties has not been suitably effective in isolating the fastest evolving classes of changes. We now propose to use the Universal index U of Tang et al. (2004) to classify the 75 elementary amino acid changes (codons differing by 1 bp) by their evolutionary exchangeability. Let Ki denote the Ka value of each class (i = 1, ..., 75 from the most to the least exchangeable). The cumulative Ki for the top 10 classes, denoted Kh (for high-exchangeability types), has two important properties: (1) Kh usually accounts for 25%-30% of total amino acid changes and (2) when the observed number of amino acid substitutions is large, Kh is predictably twice the value of Ka. This shall be referred to as the twofold approximation. The new method for estimating Kh is applied to the comparisons between human and macaque and between mouse and rat. The twofold approximation holds well in these data sets, and the signature of positive selection can be more easily discerned using the Kh statistic than using Ka. Many genes with Ka/Ks > 0.5 can now be shown to have Kh/Ks > 1 and to have evolved adaptively, at least for the high-exchangeability group of amino acid changes.

Amino Acid Substitution↗
PubMed2005

Substitution rate and structural divergence of 5'UTR evolution: comparative analysis between human and cynomolgus monkey cDNAs.

The substitution rate and structural divergence in the 5'-untranslated region (UTR) were investigated by using human and cynomolgus monkey cDNA sequences. Due to the weaker functional constraint in the UTR than in the coding sequence, the divergence between humans and macaques would provide a good estimate of the nucleotide substitution rate and structural divergence in the 5'UTR. We found that the substitution rate in the 5'UTR (K5UTR) averaged approximately 10%-20% lower than the synonymous substitution rate (Ks). However, both the K5UTR and nonsynonymous substitution rate (Ka) were significantly higher in the testicular cDNAs than in the brain cDNAs, whereas the Ks did not differ. Further, an in silico analysis revealed that 27% (169/622) of macaque testicular cDNAs had an altered exon-intron structure in the 5'UTR compared with the human cDNAs. The fraction of cDNAs with an exon alteration was significantly higher in the testicular cDNAs than in the brain cDNAs. We confirmed by using reverse transcriptase-polymerase chain reaction that about one-third (6/16) of in silico "macaque-specific" exons in the 5'UTR were actually macaque specific in the testis. The results imply that positive selection increased K5UTR and structural alteration rate of a certain fraction of genes as well as Ka. We found that both positive and negative selection can act on the 5'UTR sequences.

Animals↗
PubMed2005

Molecular criteria for determining new hybrid species--an application to the Sonneratia hybrids.

The possible hybrid origin of new species can usually be corroborated by molecular means. Here, we suggest that the segregation patterns of the molecular markers be further analyzed. A true hybrid species should show the patterns under continuous breeding among its members, at least beyond the F2 generation. We applied the guidelines to the putative hybrid species of Sonneratia, a widespread mangrove genus, and concluded that all the observed hybrids in this genus are simple F1's. Thus, S. x gulngai and S. x hainanensis are not true hybrid species. The segregation patterns of molecular markers should be heeded in interpreting the existence of hybrid species.

Base Sequence↗
PubMed2005

Evolution of sexual isolation during secondary contact: genotypic versus phenotypic changes in laboratory populations.

We monitored the phenotypic and genotypic changes that occur when two behavioral races come into contact in laboratory populations. Drosophila melanogaster from Zimbabwe and nearby regions (Z type) show strong but asymmetric sexual isolation from their cosmopolitan counterparts (M type). Crosses of Z females and M males do not take place readily when other choices are available. At least 15 loci are known to control Z-type mating preferences and performance. By thoroughly mixing the genomes of the two types in laboratory populations, we artificially created maximum secondary contact. Despite the strength of sexual selection favoring Z-type male characters, Z-type behavior is eliminated or greatly diminished in all 12 hybrid populations after only 60 generations. This trend is consistent with the spread of the M-type behavior throughout the world as well as a detailed analysis of fitness components. Surprisingly, in contrast with the phenotypic convergence toward the M-type, genotypic samples broadly covering the genomic regions of mapped behavioral loci show no such trend. The genome appears to be "fine grained," with adjacent loci having different evolutionary dynamics and genealogical histories.

Alleles↗
PubMed2005

Evolution of sexual isolation in laboratory populations: fitness differences between mating types and the associated hybrid incompatibilities.

Drosophila melanogaster is known to have two races in the incipient stages of speciation that exhibit strong asymmetric premating isolation: Zimbabwe (Z) and cosmopolitan (M). In a study examining the phenotypic and genotypic evolution after secondary contact, we found that despite strong sexual selection favoring the Z-type behavior, it is the M-type behavior that comes to dominate hybrid populations. This article examines the fitness costs associated with the Z-type behavior. We have discovered that these costs are great enough to explain the failure of the Z-type behavior to prosper. Here we report that Z-type females produce approximately half the number of offspring that M-type females produce. Furthermore, crosses between populations have revealed that Z-type females mated to M-type males have approximately 20% fewer offspring than the reciprocal crosses because of an inability of M-type sperm to successfully fertilize Z-type eggs. Hybrid crosses also exhibit much-reduced numbers of viable offspring in addition to reduced hybrid male fertility. These fitness effects suggest that multiple mechanisms of postmating isolation have evolved concurrently with the divergence in behavior.

Animals↗
PubMed2005

Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee.

The effect of weak selection driving genome evolution has attracted much attention in the last decade, but the task of measuring the strength of such selection is particularly difficult. A useful approach is to contrast the evolution of X-linked and autosomal genes in two closely related species in a whole-genome analysis. If the fitness effect of mutations is recessive, X-linked genes should evolve more rapidly than autosomal genes when the mutations are advantageous, and they should evolve more slowly than autosomal genes when the mutations are deleterious. We found synonymous substitutions on the X chromosome of human and chimpanzee to be less frequent than those on the autosomes. When calibrated against substitutions in the intergenic regions and pseudogenes to filter out the differences in the mutation rate and ancestral population size between X chromosomes and autosomes, X-linked synonymous substitutions are still 10% less frequent. At least 90% of the synonymous substitutions in human and chimpanzee are estimated to be deleterious, but the fitness effect is weaker than the effect of genetic drift. However, X-linked nonsynonymous substitutions are approximately 30% more frequent than autosomal ones, suggesting the fixation of advantageous mutations that are recessive.

Animals↗
PubMed2005

Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human.

The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002-2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003.

Amino Acid Substitution↗
PubMed2005

Detecting novel low-abundant transcripts in Drosophila.

Increasing evidence suggests that low-abundant transcripts may play fundamental roles in biological processes. In an attempt to estimate the prevalence of low-abundant transcripts in eukaryotic genomes, we performed a transcriptome analysis in Drosophila using the SAGE technique. We collected 244,313 SAGE tags from transcripts expressed in Drosophila embryonic, larval, pupae, adult, and testicular tissue. From these SAGE tags, we identified 40,823 unique SAGE tags. Our analysis showed that 55% of the 40,823 unique SAGE tags are novel without matches in currently known Drosophila transcripts, and most of the novel SAGE tags have low copy numbers. Further analysis indicated that these novel SAGE tags represent novel low-abundant transcripts expressed from loci outside of currently annotated exons including the intergenic and intronic regions, and antisense of the currently annotated exons in the Drosophila genome. Our study reveals the presence of a significant number of novel low-abundant transcripts in Drosophila, and highlights the need to isolate these novel low-abundant transcripts for further biological studies.

Animals↗
PubMed2005

Inferring the mode of speciation from genomic data: a study of the great apes.

The strictly allopatric model of speciation makes definable predictions on the pattern of divergence, one of which is the uniformity in the divergence time across genomic regions. Using 345 coding and 143 intergenic sequences from the African great apes, we were able to reject the null hypothesis that the divergence time in the coding sequences (CDSs) and intergenic sequences (IGSs) is the same between human and chimpanzee. The conclusion is further supported by the analysis of whole-genome sequences between these species. The difference suggests a prolonged period of genetic exchange during the formation of these two species. Because the analysis should be generally applicable, collecting DNA sequence data from many genomic regions between closely related species should help to settle the debate over the prevalence of the allopatric mode of speciation.

Animals↗
PubMed2004

Gene duplication and speciation in Drosophila: evidence from the Odysseus locus.

The importance of gene duplication in evolution has long been recognized. Because duplicated genes are prone to diverge in function, gene duplication could plausibly play a role in species differentiation. However, experimental evidence linking gene duplication with speciation is scarce. Here, we show that a hybrid-male sterility gene, Odysseus (OdsH), arose by gene duplication in the Drosophila genome. OdsH has evolved at a very high rate, whereas its most immediate paralog, unc-4, is nearly identical among species in the Drosophila melanogaster subgroup. The disparity in their sequence evolution is echoed by the divergence in their expression patterns in both soma and reproductive tissues. We suggest that duplicated genes that have yet to evolve a stable function at the time of speciation may be candidates for "speciation genes," which is broadly defined as genes that contribute to differential adaptation between species.

Amino Acid Sequence↗
PubMed2004

The normal function of a speciation gene, Odysseus, and its hybrid sterility effect.

To understand how postmating isolation is connected to the normal process of species divergence and why hybrid male sterility is often the first sign of speciation, we analyzed the Odysseus (OdsH) gene of hybrid male sterility in Drosophila. We carried out expression analysis, transgenic study, and gene knockout. The combined evidence suggests that the sterility phenotype represents a novel manifestation of the gene function rather than the reduction or loss of the normal one. The gene knockout experiment identified the normal function of OdsH as a modest enhancement of sperm production in young males. The implication of a weak effect of OdsH on the normal phenotype but a strong influence on hybrid male sterility is discussed in light of Haldane's rule of postmating isolation.

Animals↗
PubMed2004

A universal evolutionary index for amino acid changes.

Different nonsynonymous changes may be under different selective pressure during evolution. Of the 190 possible interchanges among the 20 amino acids, only 75 can be attained by a single-base substitution. An evolutionary index (EI) can be empirically computed for each of the 75 elementary changes as the likelihood of substitutions, relative to that of synonymous changes. We used 280, 1,306, 2,488, and 309 orthologous genes from primates (human versus Old World monkey), rodents (mouse versus rat), yeast (S. cerevisiae versus S. paradoxus), and Drosophila (D. melanogaster versus D. simulans), respectively, to estimate the EIs. In each data set, EI varies more than 10-fold, and the correlation coefficients of EIs from the pairwise comparisons are high (e.g., r = 0.91 between rodent and yeast). The high correlations suggest that the amino acid properties are strong determinants of protein evolution, irrespective of the identities of the proteins or the taxa of interest. However, these properties are not well captured in conventional measures of amino acid exchangeability. We, therefore, propose a universal index of exchange (U): for any large data set, its EI can be expressed as U*R, where R is the average Ka/Ks for that data set. The codon-based, empirically determined EI (i.e., U*R) makes much better predictions on protein evolution than do previous methods.

Amino Acids↗