Pairs Of Orthologous Sequences Research Articles

Whole Genome and Tandem Duplicate Retention Facilitated Glucosinolate Pathway Diversification in the Mustard Family

Plants share a common history of successive whole-genome duplication (WGD) events retaining genomic patterns of duplicate gene copies (ohnologs) organized in conserved syntenic blocks. Duplication was often proposed to affect the origin of novel traits during evolution. However, genetic evidence linking WGD to pathway diversification is scarce. We show that WGD and tandem duplication (TD) accelerated genetic versatility of plant secondary metabolism, exemplified with the glucosinolate (GS) pathway in the mustard family. GS biosynthesis is a well-studied trait, employing at least 52 biosynthetic and regulatory genes in the model plant Arabidopsis. In a phylogenomics approach, we identified 67 GS loci in Aethionema arabicum of the tribe Aethionemae, sister group to all mustard family members. All but one of the Arabidopsis GS gene families evolved orthologs in Aethionema and all but one of the orthologous sequence pairs exhibit synteny. The 45% fraction of duplicates among all protein-coding genes in Arabidopsis was increased to 95% and 97% for Arabidopsis and Aethionema GS pathway inventory, respectively. Compared with the 22% average for all protein-coding genes in Arabidopsis, 52% and 56% of Aethionema and Arabidopsis GS loci align to ohnolog copies dating back to the last common WGD event. Although 15% of all Arabidopsis genes are organized in tandem arrays, 45% and 48% of GS loci in Arabidopsis and Aethionema descend from TD, respectively. We describe a sequential combination of TD and WGD events driving gene family extension, thereby expanding the evolutionary playground for functional diversification and thus potential novelty and success.

Rapidly Evolving Genes and Stress Adaptation of Two Desert Poplars, Populus euphratica and P. pruinosa

Understanding which genes have evolved rapidly with the recent tree speciation in arid habitats can provide valuable insights into different adaptation mechanisms. We employed a comparative evolutionary analysis of expressed sequence tags (ESTs) from two desert poplars, Populus pruinosa and P. euphratica, which diverged in the recent past. Following an approach taken previously with P. euphratica, we conducted a deep transcriptomic analysis of P. pruinosa. To maximize representation of conditional transcripts, mRNA was obtained from living tissues of two types of callus and desert-grown trees. De novo assembly generated 114,866 high-quality unique sequences using Solexa sequence data. Following assembly we were able to identify, with high confidence, 2859 orthologous sequence pairs between the two species. Based on the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions, we identified a total of 84 (2.9%) ortholog pairs exhibiting rapid evolution with signs of strong selection (Ka/Ks>1). Genes homologous to these ortholog pairs in model species are mainly involved in ‘responses to stress’, ‘ubiquitin-dependent protein catabolic processes’, and ‘biological regulation’. Finally, we examined the expression patterns of candidate genes with rapid evolution in response to salt stress. Only one pair of orthologs up-regulated their expression in both species while three and four genes were found to up-regulated in P. pruinosa and in P. euphratica respectively. Our findings together suggest that the genes at the same category or network but with differentiated expressions or functions may have evolved rapidly during adaptive divergence of the two species to differentiated salty desert habitats.

Analysis of Protein Thermostability Enhancing Factors in Industrially ImportantThermusBacteria Species

Elucidation of evolutionary factors that enhance protein thermostability is a critical problem and was the focus of this work on Thermus species. Pairs of orthologous sequences of T. scotoductus SA-01 and T. thermophilus HB27, with the largest negative minimum folding energy (MFE) as predicted by the UNAFold algorithm, were statistically analyzed. Favored substitutions of amino acids residues and their properties were determined. Substitutions were analyzed in modeled protein structures to determine their locations and contribution to energy differences using PyMOL and FoldX programs respectively. Dominant trends in amino acid substitutions consistent with differences in thermostability between orthologous sequences were observed. T. thermophilus thermophilic proteins showed an increase in non-polar, tiny, and charged amino acids. An abundance of alanine substituted by serine and threonine, as well as arginine substituted by glutamine and lysine was observed in T. thermophilus HB27. Structural comparison showed that stabilizing mutations occurred on surfaces and loops in protein structures.

A transcriptomic scan for positively selected genes in two closely related marine fishes: Sebastes caurinus and S. rastrelliger

Comparative genomic analyses can provide valuable insight into functional evolutionary divergence among closely related species. Here we employ a comparative evolutionary analysis of expressed sequence tags (ESTs) from two closely related species of marine fishes (genus Sebastes — rockfish). Sebastes is a highly diverse group of marine fishes that inhabit a wide array of marine habitats and the study of this group can provide insights into speciation in the marine environment. ESTs were developed for S. caurinus (23,668 from brain, kidney, and spleen tissues) and S. rastrelliger (11,207 from brain and pituitary tissues). Following assembly we were able to identify, with high confidence, 257 orthologous sequence pairs between the two species through a reciprocal best hit blast search. An analysis of functional divergence between orthologs revealed that 19.46% had Ka/Ks values greater than 0.5 and 8.17% had Ka/Ks values greater than one, identifying a large pool of candidate genes to further study adaptive divergence in the group. Genes with elevated Ka/Ks values belonged to the following functional categories: immune function, metabolism, longevity, and reproductive behavior, indicating that adaptive divergence in these functional groups may be important in the diversification of this group of fishes. This study provides the ground work to better understand the molecular evolution of genes involved in a radiation of marine fishes.

Eukaryotic-like protein kinases in the prokaryotes and the myxobacterial kinome

Ser/Thr/Tyr kinases, which together comprise a major class of regulatory proteins in eukaryotes, were not believed to play an important role in prokaryotes until recently. However, our analysis of 626 prokaryotic genomes reveals that eukaryotic-like protein kinases (ELKs) are found in nearly two-thirds of the sequenced strains. We have identified 2697 ELKs, most of which are encoded by multicellular strains of the phyla Proteobacteria (Myxococcales), Actinobacteria, Cyanobacteria, and Chloroflexi, and 2 Acidobacteria and 1 Planctomycetes. Astonishingly, 7 myxobacterial strains together encode 892 ELKs, with 4 of the strains exhibiting a genomic ELK density similar to that observed in eukaryotes. Most myxobacterial ELKs show a modular organization in which the kinase domain is located at the N terminus. The C-terminal portion of the ELKs is highly diverse and often contains sequences with similarity to characterized domains, most of them involved in signaling mechanisms or in protein-protein interactions. However, many of these architectures are unique to the myxobacteria, an observation that suggests that this group exploits sophisticated and novel signal transduction systems. Phylogenetic reconstruction using the kinase domains revealed many orthologous sequence pairs and a huge number of gene duplications that probably occurred after speciation. Furthermore, studies of the microsynteny in the ELK-encoding regions reveal only low levels of synteny among Myxococcus xanthus, Plesiocystis pacifica, and Sorangium cellulosum. However, extensive similarities between M. xanthus, Stigmatella aurantiaca, and 3 Anaeromyxobacter strains were observed, indicating that they share regulatory pathways involving various ELKs.

Measuring Global Credibility with Application to Local Sequence Alignment

Computational biology is replete with high-dimensional (high-D) discrete prediction and inference problems, including sequence alignment, RNA structure prediction, phylogenetic inference, motif finding, prediction of pathways, and model selection problems in statistical genetics. Even though prediction and inference in these settings are uncertain, little attention has been focused on the development of global measures of uncertainty. Regardless of the procedure employed to produce a prediction, when a procedure delivers a single answer, that answer is a point estimate selected from the solution ensemble, the set of all possible solutions. For high-D discrete space, these ensembles are immense, and thus there is considerable uncertainty. We recommend the use of Bayesian credibility limits to describe this uncertainty, where a (1−α)%, 0≤α≤1, credibility limit is the minimum Hamming distance radius of a hyper-sphere containing (1−α)% of the posterior distribution. Because sequence alignment is arguably the most extensively used procedure in computational biology, we employ it here to make these general concepts more concrete. The maximum similarity estimator (i.e., the alignment that maximizes the likelihood) and the centroid estimator (i.e., the alignment that minimizes the mean Hamming distance from the posterior weighted ensemble of alignments) are used to demonstrate the application of Bayesian credibility limits to alignment estimators. Application of Bayesian credibility limits to the alignment of 20 human/rodent orthologous sequence pairs and 125 orthologous sequence pairs from six Shewanella species shows that credibility limits of the alignments of promoter sequences of these species vary widely, and that centroid alignments dependably have tighter credibility limits than traditional maximum similarity alignments.

The selection of acceptable protein mutations

We have determined the general constraints that govern sequence divergence in proteins that retain entirely, or very largely, the same structure and function. To do this we collected data from three different groups of orthologous sequences: those found in humans and mice, in humans and chickens, and in Escherichia coli and Salmonella enterica. In total, these organisms have 21,738 suitable pairs of orthologs, and these contain nearly 2 million mutations. The three groups differ greatly in the taxa from which they come and/or in the time that separates them from their last common ancestor. Nevertheless, the results we obtain from the three different groups are strikingly similar. For each group, the orthologous sequence pairs were assigned to six different divergence categories on the basis of their sequence identities. For categories with the same divergence, common accepted mutations have similar frequencies and rank orders in the three groups. With divergence, the width of the range of common mutations grows in the same manner in each group. We examined the distribution of mutations in protein structures. With increasing divergence, mutations increase at different rates in the buried, intermediate, and exposed regions of protein structures in a manner that explains the exponential relationship between the divergence of structure and sequence. This work implies that commonly allowed mutations are selected by a set of general constraints that are well defined and whose nature varies with divergence.

Genome-Wide Search of Gene Conversions in Duplicated Genes of Mouse and Rat

Gene conversion is considered to play important roles in the formation of genomic makeup such as homogenization of multigene families and diversification of alleles. We devised two statistical tests on quartets for detecting gene conversion events. Each "quartet" consists of two pairs of orthologous sequences supposed to have been generated by a duplication event and a subsequent speciation of two closely related species. As example data, EnsEMBL mouse and rat cDNA sequences were used to obtain a genome-wide picture of gene conversion events. We extensively sampled 2,641 quartets that appear to have resulted from duplications after the divergence of primates and rodents and before mouse-rat speciation. Combination of our new tests with Sawyer's and Takahata's tests enhanced the detection sensitivity while keeping false positives as few as possible. About 18% (488 quartets) were shown to be highly positive for gene conversion using this combined test. Out of them, 340 (13% of the total) showed signs of gene conversion in mouse sequence pairs. Those gene conversion-positive gene pairs are mostly linked in the same chromosomes, with the proportion of positive pairs in the linked and unlinked categories being 15% and 1%, respectively. Statistical analyses showed that (1) the susceptibility to gene conversion correlates negatively with the physical distance, especially the frequency of 29% was observed for gene pairs whose distances are smaller than 55 kb; (2) the occurrence of gene conversions does not depend on the transcriptional direction; (3) small gene families consisting of between three and six contiguous genes are highly prone to gene conversion; and (4) frequency of gene conversions greatly varies depending on functional categories, and cadherins favor gene conversion, while vomeronasal receptors type 1 and immunoglobulin V-type proteins disfavor it. These findings will be useful to deepen the understanding of the roles of gene conversion.