Genome reduction as the dominant mode of evolution

A common belief is that evolution generally proceeds towards greater complexity at both the organismal and the genomic level, numerous examples of reductive evolution of parasites and symbionts notwithstanding. However, recent evolutionary reconstructions challenge this notion. Two notable examples are the reconstruction of the complex archaeal ancestor and the intron‐rich ancestor of eukaryotes. In both cases, evolution in most of the lineages was apparently dominated by extensive loss of genes and introns, respectively. These and many other cases of reductive evolution are consistent with a general model composed of two distinct evolutionary phases: the short, explosive, innovation phase that leads to an abrupt increase in genome complexity, followed by a much longer reductive phase, which encompasses either a neutral ratchet of genetic material loss or adaptive genome streamlining. Quantitatively, the evolution of genomes appears to be dominated by reduction and simplification, punctuated by episodes of complexification.     

Census of orthologous genes and self-organizing maps of biologically relevant transcriptional patterns in chickens (Gallus gallus)

The launch of large-scale chicken expressed sequence tags (EST) projects has placed the chicken in the lead for the number of EST sequences in agriculturally important animals. More than 451,000 chicken ESTs derived from over 158 libraries have been deposited in the NCBI dbEST database as of December 2003. But how many genes these ESTs represent and how they are expressed in different chicken tissues/organs remain undetermined. In the present research, we developed a human gene-based strategy for census of chicken orthologous genes and identification of their expression patterns. Among 34,157 human coding genes used in the study, BLAST analysis revealed that 11,066 genes provisionally matched 248,628 chicken ESTs. Based on the average EST abundance of the orthologous genes, the current public repository of chicken ESTs could represent 20,000 provisional genes. Analysis of gene expression in 14 single tissues/organs showed that approximately 15% of genes were expressed exclusively in single tissue/organ whereas the remaining 85% of genes were co-expressed in two or more tissues/organs. A majority (91.15%) of genes expressed in chicken embryos were also expressed at post-hatch stages, indicating that most genes activated in chicken embryos could serve housekeeping functions. Self-organizing maps (SOM) analysis organized 8807 provisional genes in selected chicken tissues into 98 clusters with each cluster being indicative of common regulatory factors and pathways. A total of 969 provisional orthologous genes were identified as preferentially expressed genes (PEGs) in various chicken tissues/organs (LOD>3.0). No doubt, the present study on gene expression patterns will provide insight into dynamics of metabolic pathways and tissue/organ programming and reprogramming in chickens.     

Using all Gene Families Vastly Expands Data Available for Phylogenomic Inference

Traditionally, single-copy orthologs have been the gold standard in phylogenomics. Most phylogenomic studies identify putative single-copy orthologs using clustering approaches and retain families with a single sequence per species. This limits the amount of data available by excluding larger families. Recent advances have suggested several ways to include data from larger families. For instance, tree-based decomposition methods facilitate the extraction of orthologs from large families. Additionally, several methods for species tree inference are robust to the inclusion of paralogs and could use all of the data from larger families. Here, we explore the effects of using all families for phylogenetic inference by examining relationships among 26 primate species in detail and by analyzing five additional data sets. We compare single-copy families, orthologs extracted using tree-based decomposition approaches, and all families with all data. We explore several species tree inference methods, finding that identical trees are returned across nearly all subsets of the data and methods for primates. The relationships among Platyrrhini remain contentious; however, the species tree inference method matters more than the subset of data used. Using data from larger gene families drastically increases the number of genes available and leads to consistent estimates of branch lengths, nodal certainty and concordance, and inferences of introgression in primates. For the other data sets, topological inferences are consistent whether single-copy families or orthologs extracted using decomposition approaches are analyzed. Using larger gene families is a promising approach to include more data in phylogenomics without sacrificing accuracy, at least when high-quality genomes are available.     

Reverse polarization in amino acid and nucleotide substitution patterns between human-mouse orthologs of two compositional extrema.

Genome-wide analysis of sequence divergence patterns in 12,024 human-mouse orthologous pairs reveals, for the first time, that the trends in nucleotide and amino acid substitutions in orthologs of high and low GC composition are highly asymmetric and polarized to opposite directions. The entire dataset has been divided into three groups on the basis of the GC content at third codon sites of human genes: high, medium, and low. High-GC orthologs exhibit significant bias in favor of the replacements, Thr --> Ala, Ser --> Ala, Val --> Ala, Lys --> Arg, Asn --> Ser, Ile --> Val etc., from mouse to human, whereas in low-GC orthologs, the reverse trends prevail. In general, in the high-GC group, residues encoded by A/U-rich codons of mouse proteins tend to be replaced by the residues encoded by relatively G/C-rich codons in their human orthologs, whereas the opposite trend is observed among the low-GC orthologous pairs. The medium-GC group shares some trends with high-GC group and some with low-GC group. The only significant trend common in all groups of orthologs, irrespective of their GC bias, is (Asp)(Mouse) --> (Glu)(Human) replacement. At the nucleotide level, high-GC orthologs have undergone a large excess of (A/T)(Mouse) --> (G/C)(Human) substitutions over (G/C)(Mouse) --> (A/T)(Human) at each codon position, whereas for low-GC orthologs, the reverse is true.     

A protein-specifically adapted scoring function for the reranking of docking solutions

In this work, we developed a protein-specifically adapted scoring function and applied it to the reranking of protein-protein docking solutions generated with a conventional docking program. The approach was validated using experimentally determined structures of the bacterial HPr-protein in complex with four structurally nonhomologous binding partners as an example. A sufficiently large data basis for the generation of protein-specifically adapted pair potentials was generated by modeling all orthologous complexes for each type of interaction resulting in a total of 224 complexes. The parameters for potential generation were systematically varied and resulted in a total of 66,132 different scoring functions that were tested for their ability of successful reranking of 1000 docking solutions generated from modeled structures of the unbound binding partners. Parameters that proved critical for the generation of good scoring functions were the distance cutoff used for the generation of the pair potential, and an additional cutoff that allows a proper weighting of conserved and nonconserved contacts in the interface. Compared to the original scoring function, application of this novel type of scoring functions resulted in a significant accumulation of acceptable docking solutions within the first 10 ranks. Depending on the type of complex investigated one to five acceptable complex geometries are found among the 10 highest-ranked solutions and for three of the four systems tested, an acceptable solution was placed on the first rank.     

Clustering orthologous proteins across phylogenetically distant species

The quality of orthologous protein clusters (OPCs) is largely dependent on the results of the reciprocal BLAST (basic local alignment search tool) hits among genomes. The BLAST algorithm is very efficient and fast, but it is very difficult to get optimal solution among phylogenetically distant species because the genomes with large evolutionary distance typically have low similarity in their protein sequences. To reduce the false positives in the OPCs, thresholding is often employed on the BLAST scores. However, the thresholding also eliminates large numbers of true positives as the orthologs from distant species likely have low BLAST scores. To rectify this problem, we introduce a new hybrid method combining the Recursive and the Markov CLuster (MCL) algorithms without using the BLAST thresholding. In the first step, we use InParanoid to produce n(n-1)/2 ortholog tables from n genomes. After combining all the tables into one, our clustering algorithm clusters ortholog pairs recursively in the table. Then, our method employs MCL algorithm to compute the clusters and refines the clusters by adjusting the inflation factor. We tested our method using six different genomes and evaluated the results by comparing against Kegg Orthology (KO) OPCs, which are generated from manually curated pathways. To quantify the accuracy of the results, we introduced a new intuitive similarity measure based on our Least-move algorithm that computes the consistency between two OPCs. We compared the resulting OPCs with the KO OPCs using this measure. We also evaluated the performance of our method using InParanoid as the baseline approach. The experimental results show that, at the inflation factor 1.3, we produced 54% more orthologs than InParanoid sacrificing a little less accuracy (1.7% less) than InParanoid, and at the factor 1.4, produced not only 15% more orthologs than InParanoid but also a higher accuracy (1.4% more) than InParanoid.     

Greatly reduced phylogenetic structure in the cultivated potato clade (Solanum section Petota pro parte)

Premise of the Study

The species boundaries of wild and cultivated potatoes are controversial, with most of the taxonomic problems in the cultivated potato clade. We here provide the first in‐depth phylogenetic study of the cultivated potato clade to explore possible causes of these problems.

Methods

We examined 131 diploid accessions, using 12 nuclear orthologs, producing an aligned data set of 14,072 DNA characters, 2171 of which are parsimony‐informative. We analyzed the data to produce phylogenies and perform concordance analysis and goodness‐of‐fit tests.

Key Results

There is good phylogenetic structure in clades traditionally referred to as clade 1+2 (North and Central American diploid potatoes exclusive of Solanum verrucosum), clade 3, and a newly discovered basal clade, but drastically reduced phylogenetic structure in clade 4, the cultivated potato clade. The results highlight a clade of species in South America not shown before, ‘neocardenasii’, sister to clade 1+2, that possesses key morphological traits typical of diploids in Mexico and Central America. Goodness‐of‐fit tests suggest potential hybridization between some species of the cultivated potato clade. However, we do not have enough phylogenetic signal with the data at hand to explicitly estimate such hybridization events with species networks methods.

Conclusions

We document the close relationships of many of the species in the cultivated potato clade, provide insight into the cause of their taxonomic problems, and support the recent reduction of species in this clade. The discovery of the neocardenasii clade forces a reevaluation of a hypothesis that section Petota originated in Mexico and Central America.     

F-box基因拷贝数目变异的机制研究:以12种果蝇为例

拷贝数目变异是一种对表型变异和生物进化具有重要意义的基因组结构变异.以前的研究表明不同物种中F-box基因的拷贝数目差异较大.为了深入探索拷贝数目变异的式样和机制.我们以12个果蝇近缘种为研究对象,分析了F-box基因的系统发育关系、进化式样以及它们在染色体上的位置.结果发现,虽然各个物种中F-box基因的拷贝数目差别不大(42-47个),但是仍然存在着很多引起拷贝数目变异的基因获得和丢失事件.这说明表面上变化不大的拷贝数目在一定程度上掩盖了频繁发生的基因获得和丢失事件.通过比较这些基因在染色体上的位置,发现只有在亲缘关系很近的物种之间才能鉴定出有明显微共线性关系的基因组区段.我们还发现,造成F-box基因拷贝数目增加的主要机制是散在重复和串联重复,而反转录转座和新基因的非编码区起源也是两种值得注意的机制.此外,序列变异导致的外显子边界变化以及外显子丢失是引起拷贝数目减少的两种机制.在12种果蝇的最近共同祖先中,F-box基因的拷贝数目与现存物种基本相似,但是基因的获得和丢失事件使得现存物种中的F-box基因在构成上已经有了明显的差别.对数目变异的式样及其与基因功能的关系的研究表明,拷贝数目变异是F-box基因家族"生与死"的进化在基因组层面的系统反映,并有可能为表型变异提供了原始材料.     

Short-chain dehydrogenase/reductase (SDR) relationships: a large family with eight clusters common to human, animal, and plant genomes

The progress in genome characterizations has opened new routes for studying enzyme families. The availability of the human genome enabled us to delineate the large family of short-chain dehydrogenase/reductase (SDR) members. Although the human genome releases are not yet final, we have already found 63 members. We have also compared these SDR forms with those of three model organisms: Caenorhabditis elegans, Drosophila melanogaster, and Arabidopsis thaliana. We detect eight SDR ortholog clusters in a cross-genome comparison. Four of these clusters represent extended SDR forms, a subgroup found in all life forms. The other four are classical SDRs with activities involved in cellular differentiation and signalling. We also find 18 SDR genes that are present only in the human genome of the four genomes studied, reflecting enzyme forms specific to mammals. Close to half of these gene products represent steroid dehydrogenases, emphasizing the regulatory importance of these enzymes.     

Intracellular trafficking of Notch receptors and ligands

The Notch pathway represents a highly conserved signaling network, which regulates the formation and maintenance of various organ systems along development and during adulthood. Direct cell-cell contacts between ligand- and receptor-expressing cells underlie activation of the Notch pathway. Notch signaling requires endocytosis in both signal emitting and receiving cells. Recent findings on the roles of a number of modulators show that they act either on the maintenance of an active receptor at the membrane, or on the production of active ligand, or on signal transduction after activation.