Short- and Long-term Evolutionary Dynamics of Bacterial Insertion Sequences: Insights from Wolbachia Endosymbionts

Transposable elements (TE) are one of the major driving forces of genome evolution, raising the question of the long-term dynamics underlying their evolutionary success. Long-term TE evolution can readily be reconstructed in eukaryotes, thanks to many degraded copies constituting genomic fossil records of past TE proliferations. By contrast, bacterial genomes usually experience high sequence turnover and short TE retention times, thereby obscuring ancient TE evolutionary patterns. We found that Wolbachia bacterial genomes contain 52–171 insertion sequence (IS) TEs. IS account for 11% of Wolbachia wRi, which is one of the highest IS genomic coverage reported in prokaryotes to date. We show that many IS groups are currently expanding in various Wolbachia genomes and that IS horizontal transfers are frequent among strains, which can explain the apparent synchronicity of these IS proliferations. Remarkably, >70% of Wolbachia IS are nonfunctional. They constitute an unusual bacterial IS genomic fossil record providing direct empirical evidence for a long-term IS evolutionary dynamics following successive periods of intense transpositional activity. Our results show that comprehensive IS annotations have the potential to provide new insights into prokaryote TE evolution and, more generally, prokaryote genome evolution. Indeed, the identification of an important IS genomic fossil record in Wolbachia demonstrates that IS elements are not always of recent origin, contrary to the conventional view of TE evolution in prokaryote genomes. Our results also raise the question whether the abundance of IS fossils is specific to Wolbachia or it may be a general, albeit overlooked, feature of prokaryote genomes

Intense Transpositional Activity of Insertion Sequences in an Ancient Obligate Endosymbiont

The streamlined genomes of ancient obligate endosymbionts generally lack transposable elements, such as insertion sequences (IS). Yet, the genome of Wolbachia, one of the most abundant bacterial endosymbionts on Earth, is littered with IS. Such a paradox raises the question as to why there are so many ISs in the genome of this ancient endosymbiont. To address this question, we investigated IS transpositional activity in the unculturable Wolbachia by tracking the evolutionary dynamics and history of ISWpi1 elements. We show that 1) ISWpi1 is widespread in Wolbachia, being present in at least 55% of the 40 sampled strains, 2) ISWpi1 copies exhibit virtually identical nucleotide sequences both within and among Wolbachia genomes and possess an intact transposase gene, 3) individual ISWpi1 copies are differentially inserted among Wolbachia genomes, and 4) ISWpi1 occurs at variable copy numbers among Wolbachia genomes. Collectively, our results provide compelling evidence for intense ISWpi1 transpositional activity and frequent ISWpi1 horizontal transmission among strains during recent Wolbachia evolution. Thus, the genomes of ancient obligate endosymbionts can carry high loads of functional and transpositionally active transposable elements. Our results also indicate that Wolbachia genomes have experienced multiple and temporally distinct ISWpi1 invasions during their evolutionary history. Such recurrent exposition to new IS invasions may explain, at least partly, the unusually high density of transposable elements found in the genomes of Wolbachia endosymbionts

Retrotransposition of Alu elements: How many sources?

It is generally thought that only a few Alu elements are capable of retrotransposition and that these \u27master\u27 sources produce inactive copies. Here, we use a network phylogenetic approach to demonstrate that recently integrated human-specific Alu subfamilies typically contain 10-20% of secondary source elements that contributed 20-40% of all subfamily members. This multiplicity of source elements provides new insight into the remarkably successful amplification strategy of the Alu family

Insertion and Deletion Processes in Recent Human History

Background: Although insertions and deletions (indels) account for a sizable portion of genetic changes within and among species, they have received little attention because they are difficult to type, are alignment dependent and their underlying mutational process is poorly understood. A fundamental question in this respect is whether insertions and deletions are governed by similar or different processes and, if so, what these differences are. Methodology/Principal Findings: We use published resequencing data from Seattle SNPs and NIEHS human polymorphism databases to construct a genomewide data set of short polymorphic insertions and deletions in the human genome (n = 6228). We contrast these patterns of polymorphism with insertions and deletions fixed in the same regions since the divergence of human and chimpanzee (n = 10546). The macaque genome is used to resolve all indels into insertions and deletions. We find that the ratio of deletions to insertions is greater within humans than between human and chimpanzee. Deletions segregate at lower frequency in humans, providing evidence for deletions being under stronger purifying selection than insertions. The insertion and deletion rates correlate with several genomic features and we find evidence that both insertions and deletions are associated with point mutations. Finally, we find no evidence for a direct effect of the local recombination rate on the insertion and deletion rate. Conclusions/Significance: Our data strongly suggest that deletions are more deleterious than insertions but that insertion

Recently integrated Alu retrotransposons are essentially neutral residents of the human genome

Alu elements represent the largest family of human mobile elements in copy number. A controversial issue with implications for both Alu biology and human genome evolution is whether selective pressures are affecting Alu elements on a large scale. To address this issue, we analyzed the genomic distribution of the three youngest known human Alu subfamilies (Ya5a2, Ya8 and Yb9) in conjunction with their insertion polymorphism status in the human population, since selection can only act on polymorphic elements. Our results indicate that: (i) polymorphic and fixed recently integrated Alu elements are found in genomic regions whose GC contents are statistically indistinguishable, and (ii) recently integrated Alu elements are inserted randomly, regardless of the GC content of the surrounding genomic DNA. These results provide strong evidence that recently integrated young Alu elements are not subject to positive or negative selection on a large scale. Therefore, young Alu elements can be regarded as essentially neutral residents of the human genome. These results also imply that selective processes specifically targeting Alu elements can be ruled out as explanations for the accumulation of Alu elements in GC-rich regions of the human genome. © 2006 Elsevier B.V. All rights reserved

Estimating the retrotransposition rate of human Alu elements

Mobile elements such as Alu repeats have substantially altered the architecture of the human genome, and de novo mobile element insertions sometimes cause genetic disorders. Previous estimates for the retrotransposition rate (RR) of Alu elements in humans of one new insertion every ∼100-125 births were developed prior to the sequencing of the human and chimpanzee genomes. Here, we used two independent methods (based on the new genomic data and on disease-causing de novo Alu insertions) to generate refined Alu RR estimates in humans. Both methods consistently yielded RR on the order of one new Alu insertion every ∼20 births, despite the fact that the evolutionary-based method represents an average RR over the past ∼6 million years while the mutation-based method better reflects the current-day RR. These results suggest that Alu elements retrotranspose at a faster rate in humans than previously thought, and support the potential of Alu elements as mutagenic factors in the human genome. © 2006 Elsevier B.V. All rights reserved

In search of polymorphic Alu insertions with restricted geographic distributions

Alu elements are transposable elements that have reached over one million copies in the human genome. Some Alu elements inserted in the genome so recently that they are still polymorphic for insertion presence or absence in human populations. Recently, there has been an increasing interest in using Alu variation for studies of human population genetic structure and inference of individual geographic origin. Currently, this requires a high number of Alu loci. Here, we used a linker-mediated polymerase chain reaction method to preferentially identify low-frequency Alu elements in various human DNA samples with different geographic origins. The candidate Alu loci were subsequently genotyped in 18 worldwide human populations (∼370 individuals), resulting in the identification of two new Alu insertions restricted to populations of African ancestry. Our results suggest that it may ultimately become possible to correctly infer the geographic affiliation of unknown samples with high levels of confidence without having to genotype as many as 100 Alu loci. This is desirable if Alu insertion polymorphisms are to be used for human evolution studies or forensic applications. © 2007 Elsevier Inc. All rights reserved