Biomedical subjects

Dan Graur

Publications and source records attributed to Dan Graur.

25 records · Page 2Linked to original sources

PubMed2003

Bacterial type III secretion systems are ancient and evolved by multiple horizontal-transfer events.

Type III secretion systems (TTSS) are unique bacterial mechanisms that mediate elaborate interactions with their hosts. The fact that several of the TTSS proteins are closely related to flagellar export proteins has led to the suggestion that TTSS had evolved from flagella. Here we reconstruct the evolutionary history of four conserved type III secretion proteins and their phylogenetic relationships with flagellar paralogs. Our analysis indicates that the TTSS and the flagellar export mechanism share a common ancestor, but have evolved independently from one another. The suggestion that TTSS genes have evolved from genes encoding flagellar proteins is effectively refuted. A comparison of the species tree, as deduced from 16S rDNA sequences, to the protein phylogenetic trees has led to the identification of several major lateral transfer events involving clusters of TTSS genes. It is hypothesized that horizontal gene transfer has occurred much earlier and more frequently than previously inferred for TTSS genes and is, consequently, a major force shaping the evolution of species that harbor type III secretion systems.

Bacteria↗

PubMed2003

Evolutionary dynamics of large numts in the human genome: rarity of independent insertions and abundance of post-insertion duplications.

We determined the phylogenetic positions of 82 large nuclear pseudogenes of mitochondrial origin (numts) within the human genome. For each numt, two possibilities pertaining to its origin were considered: (1) independent insertion from the mitochondria into the nucleus, or (2) genomic duplication subsequent to the insertion. A significant increase in the rate of numt accumulation is seen after the divergence of Platyrrhini (New World monkeys) from the Catarrhini (Old World monkeys, apes and humans). By using pairwise phylogenetic analyses, we were able to demonstrate that this peak in numt accumulation is mostly the result of duplication of preexisting nuclear numts rather than the result of an increase in mitochondrial-sequence insertion. In fact, only about a third of all the numt repertoire in the human nuclear genome is due to insertions of mitochondrial sequences, the rest originated as duplications of preexisting numts. Hence, we conclude that numt insertion occurs at a much lower rate than previously reported. As expected under the assumption that genomic duplications occur at rates that are uninfluenced by content, older numts were found to be duplicated more times than recently inserted ones.

DNA Transposable Elements↗

PubMed2002

Playing chicken (Gallus gallus): methodological inconsistencies of molecular divergence date estimates due to secondary calibration points.

For any given taxonomic divergence event, one may find in the literature a wide range of time estimates. Many factors contribute to the variation in molecular date estimates for the same evolutionary event. High on the list is the choice of calibration points for converting genetic distances into evolutionary rates and, subsequently, into dates of divergence. In this study, we investigate one critical source of error in estimating divergence times, i.e. the use of secondary calibration points, which are divergence time estimates that have been derived from one molecular dataset on the basis of a primary external calibration point, and which are used again independently of the original external calibration point on a second dataset. Unless particular care is exercised, this practice leads to internal inconsistencies, and the inferred dates of divergence are by necessity unreliable. We present a consistency test for assessing the reliability of divergence time estimates based on secondary calibration points. As a case study, we examine recent estimates of divergence times among phyla and kingdoms based on multiple nuclear protein-coding genes, and show that they fail the consistency test.

Amino Acid Substitution↗

PubMed2002

The evolutionary history of prosaposin: two successive tandem-duplication events gave rise to the four saposin domains in vertebrates.

Prosaposin is a multifunctional protein encoded by a single-copy gene. It contains four saposin domains (A, B, C, and D) occurring as tandem repeats connected by linker sequences. Because the saposin domains are similar to one another, it is deduced that they were created by sequential duplications of an ancestral domain. There are two types of evolutionary scenarios that may explain the creation of the four-domain gene: (1) two rounds of tandem internal gene duplication and (2) three rounds of duplications. An evolutionary and phylogenetic analysis of saposin DNA and amino acid sequences from human, mouse, rat, chicken, and zebrafish indicates that the first evolutionary scenario is the most likely. Accordingly, an ancestral saposin-unit duplication produced a two-domain gene, which, subsequently, underwent a second complete tandem duplication to give rise to the present four-domain structure of the prosaposin gene.

Amino Acid Sequence↗

PubMed2002

A branch-and-bound algorithm for the inference of ancestral amino-acid sequences when the replacement rate varies among sites: Application to the evolution of five gene families.

MOTIVATION: We developed an algorithm to reconstruct ancestral sequences, taking into account the rate variation among sites of the protein sequences. Our algorithm maximizes the joint probability of the ancestral sequences, assuming that the rate is gamma distributed among sites. Our algorithm probably finds the global maximum. The use of 'joint' reconstruction is motivated by studies that use the sequences at all the internal nodes in a phylogenetic tree, such as, for instance, the inference of patterns of amino-acid replacement, or tracing the biochemical changes that occurred during the evolution of a given protein family. RESULTS: We give an algorithm that guarantees finding the global maximum. The efficient search method makes our method applicable to datasets with large number sequences. We analyze ancestral sequences of five gene families, exploring the effect of the amount of among-site-rate-variation, and the degree of sequence divergence on the resulting ancestral states. AVAILABILITY AND SUPPLEMENTARY INFORMATION: http://evolu3.ism.ac.jp/~tal/ CONTACT: tal@ism.ac.jp

Algorithms↗

PubMed2002

Ratios of radical to conservative amino acid replacement are affected by mutational and compositional factors and may not be indicative of positive Darwinian selection.

The ratio of radical to conservative amino acid replacements is frequently used to infer positive Darwinian selection. This method is based on the assumption that radical replacements are more likely than conservative replacements to improve the function of a protein. Therefore, if positive selection plays a major role in the evolution of a protein, one would expect the radical-conservative ratio to exceed the expectation under neutrality. Here, we investigate the possibility that factors unrelated to selection, i.e., transition-transversion ratio, codon usage, genetic code, and amino acid composition, influence the radical-conservative replacement ratio. All factors that have been studied were found to affect the radical-conservative replacement ratio. In particular, amino acid composition and transition-transversion ratio are shown to have the most profound effects. Because none of the studied factors had anything to do with selection (positive or otherwise) and also because all of them (singly or in combination) affected a measure that was supposed to be indicative of positive selection, we conclude that selectional inferences based on radical-conservative replacement ratios should be treated with suspicion.

Amino Acid Substitution↗

PubMed2002

Alu-containing exons are alternatively spliced.

Alu repetitive elements are found in approximately 1.4 million copies in the human genome, comprising more than one-tenth of it. Numerous studies describe exonizations of Alu elements, that is, splicing-mediated insertions of parts of Alu sequences into mature mRNAs. To study the connection between the exonization of Alu elements and alternative splicing, we used a database of ESTs and cDNAs aligned to the human genome. We compiled two exon sets, one of 1176 alternatively spliced internal exons, and another of 4151 constitutively spliced internal exons. Sixty one alternatively spliced internal exons (5.2%) had a significant BLAST hit to an Alu sequence, but none of the constitutively spliced internal exons had such a hit. The vast majority (84%) of the Alu-containing exons that appeared within the coding region of mRNAs caused a frame-shift or a premature termination codon. Alu-containing exons were included in transcripts at lower frequencies than alternatively spliced exons that do not contain an Alu sequence. These results indicate that internal exons that contain an Alu sequence are predominantly, if not exclusively, alternatively spliced. Presumably, evolutionary events that cause a constitutive insertion of an Alu sequence into an mRNA are deleterious and selected against.

Alternative Splicing↗