Retrotransposon mediated genomic fluidity in the human and chimpanzee lineages

LINE-1s (Long interspersed elements or L1s) and Alus are highly successful non-long terminal repeat retrotransposons with copy numbers of ~520,000 and \u3e1 million within the human genome, respectively. They are associated with human genetic variation and genomic rearrangement. Although they are abundant throughout primate genomes, their propagation strategy remains poorly understood. The recently released human and chimpanzee draft genome sequences provide the opportunity to compare the human genome with the chimpanzee genome. Thus, we were able to assess how these elements expanded in primate genomes and how they create genomic instability during their integration into the host genome as well as subsequent post-insertion recombination between elements. To understand the expansion of Alu elements, we first analyzed the evolutionary history of the AluYb lineage which is one of most active Alu lineages in the human genome. We suggest that the evolutionary success of Alu elements is driven at least in part by “stealth driver” elements that maintain low retrotransposition activity over extended periods of time and occasionally produce short-lived hyperactive copies responsible for the formation and remarkable expansion of Alu elements within the genome. Second, we conducted a detailed characterization of chimpanzee-specific L1 subfamily diversity. Our results showed that L1 elements have experienced different evolutionary fates in humans and chimpanzees lineages. These differential evolutionary paths may be the result of random variation or the product of competition between L1 subfamily lineages. Third, we report 50 deletion events in human and chimpanzee genomes directly linked to the insertion of L1 elements, resulting in the loss of ~18 kb of human genomic sequence and ~15 kb of chimpanzee genomic sequence. This study provides the basis for developing models of the mechanisms for small and large L1 insertion-mediated deletions. Fourth, we analyzed the magnitude of Alu recombination-mediated deletions in the human lineage subsequent to the human-chimpanzee divergence. We identified 492 human-specific deletions (for a total of ~400 kb of sequence) attributable to this process. The majority of the deletions coincide with known or predicted genes, which implicates this process in creating a substantial portion of the genomic differences between humans and chimpanzees

High Levels of Sequence Diversity in the 5′ UTRs of Human-Specific L1 Elements

Approximately 80 long interspersed element (LINE-1 or L1) copies are able to retrotranspose actively in the human genome, and these are termed retrotransposition-competent L1s. The 5′ untranslated region (UTR) of the human-specific L1 contains an internal promoter and several transcription factor binding sites. To better understand the effect of the L1 5′ UTR on the evolution of human-specific L1s, we examined this population of elements, focusing on the sequence diversity and accumulated substitutions within their 5′ UTRs. Using network analysis, we estimated the age of each L1 component (the 5′ UTR, ORF1, ORF2, and 3′ UTR). Through the comparison of the L1 components based on their estimated ages, we found that the 5′ UTR of human-specific L1s accumulates mutations at a faster rate than the other components. To further investigate the L1 5′ UTR, we examined the substitution frequency per nucleotide position among them. The results showed that the L1 5′ UTRs shared relatively conserved transcription factor binding sites, despite their high sequence diversity. Thus, we suggest that the high level of sequence diversity in the 5′ UTRs could be one of the factors controlling the number of retrotransposition-competent L1s in the human genome during the evolutionary battle between L1s and their host genomes

Allele frequencies of the human platelet antigen-1 in the Egyptian population

<p>Abstract</p> <p>Background</p> <p>The human platelet alloantigen system HPA-1 in the Egyptian population was examined by polymerase chain reaction using sequence-specific primers (PCR-SSP). The objectives of this study were to evaluate the allele frequency of HPA-1a and -1b in healthy Egyptian individuals and compare these with the international literature. Human platelet antigen (HPA) systems are associated with alloimmunization and organ transplantation rejection as well as the development of cardiovascular disease. Of the various HPA systems, HPA-1 specifically has been considered to be the most important antigenic system implicated in the Caucasian population. No study has yet examined this system in the Egyptian populations, however. We therefore investigated the allele frequency of the HPA-1 system in the Egyptian population.</p> <p>Findings</p> <p>To determine the allele frequency of the HPA-1a and -1b, we tested genomic DNAs from 206 healthy, unrelated Egyptian individuals using PCR-SSP. Our results showed that the 1a/1a genotype was the most predominant (59.22%) followed by 1a/1b (34.95%) and 1b/1b (5.83%) with allele frequencies for 1a and 1b of 0.77 and 0.23, respectively, in the population.</p> <p>Conclusion</p> <p>As compared with other geographic groups, a relatively high allele frequency of the HPA-1b in the Egyptian population may indicate a higher risk of alloimmunization. This study is the first to investigate the allele frequency of the HPA-1 system in the Egyptian population and serves as an outline for future clinical research associated with platelet disorders in this group.</p

Identification of a Genomic Reservoir for New TRIM Genes in Primate Genomes

Tripartite Motif (TRIM) ubiquitin ligases act in the innate immune response against viruses. One of the best characterized members of this family, TRIM5α, serves as a potent retroviral restriction factor with activity against HIV. Here, we characterize what are likely to be the youngest TRIM genes in the human genome. For instance, we have identified 11 TRIM genes that are specific to humans and African apes (chimpanzees, bonobos, and gorillas) and another 7 that are human-specific. Many of these young genes have never been described, and their identification brings the total number of known human TRIM genes to approximately 100. These genes were acquired through segmental duplications, most of which originated from a single locus on chromosome 11. Another polymorphic duplication of this locus has resulted in these genes being copy number variable within the human population, with a Han Chinese woman identified as having 12 additional copies of these TRIM genes compared to other individuals screened in this study. Recently, this locus was annotated as one of 34 “hotspot” regions that are also copy number variable in the genomes of chimpanzees and rhesus macaques. Most of the young TRIM genes originating from this locus are expressed, spliced, and contain signatures of positive natural selection in regions known to determine virus recognition in TRIM5α. However, we find that they do not restrict the same retroviruses as TRIM5α, consistent with the high degree of divergence observed in the regions that control target specificity. We propose that this recombinationally volatile locus serves as a reservoir from which new TRIM genes arise through segmental duplication, allowing primates to continually acquire new antiviral genes that can be selected to target new and evolving pathogens

Endonuclease-independent insertion provides an alternative pathway for L1 retrotransposition in the human genome

LINE-1 elements (L1s) are a family of highly successful retrotransposons comprising ∼ 17% of the human genome, the majority of which have inserted through an endonuclease-dependent mechanism termed target-primed reverse transcription. Recent in vitro analyses suggest that in the absence of non-homologous end joining proteins, L1 elements may utilize an alternative, endonuclease-independent pathway for insertion. However, it remains unknown whether this pathway operates in vivo or in cell lines where all DNA repair mechanisms are functional. Here, we have analyzed the human genome to demonstrate that this alternative pathway for L1 insertion has been active in recent human evolution and characterized 21 loci where L1 elements have integrated without signs of endonuclease-related activity. The structural features of these loci suggest a role for this process in DNA double-strand break repair. We show that endonuclease-independent L1 insertions are structurally distinguishable from classical L1 insertion loci, and that they are associated with inter-chromosomal translocations and deletions of target genomic DNA. © 2007 The Author(s)

Tributyrin and anise mixture supplementation improves growth performance, nutrient digestibility, jejunal villus height, and fecal microbiota in weaned pigs

IntroductionThe objective of this study was to investigate the effects of dietary supplementation of tributyrin and anise mixture (TA) on growth performance, apparent nutrient digestibility, fecal noxious gas emission, fecal score, jejunal villus height, hematology parameters, and fecal microbiota of weaned pigs.MethodsA total of 150 21-day-old crossbred weaned pigs [(Landrace × Yorkshire) × Duroc] were used in a randomized complete block design experiment. All pigs were randomly assigned to 3 groups based on the initial body weight (6.19 ± 0.29 kg). Each group had 10 replicate pens with 5 pigs (three barrows and two gilts) per pen. The experimental period was 42 days and consisted of 3 phases (phase 1, days 1–7; phase 2, days 8–21; phase 3, days 22–42). Dietary treatments were based on a corn-soybean meal-basal diet and supplemented with 0.000, 0.075, or 0.150% TA.Results and discussionWe found that dietary supplementation of graded levels of TA linearly improved body weight, body weight gain, average daily feed intake, and feed efficiency (P &lt; 0.05). TA supplementation also had positive effects on apparent dry matter, crude protein, and energy digestibility (P &lt; 0.05) and jejunal villus height (P &lt; 0.05). The emission of ammonia from feces decreased linearly with the dose of TA increased (P &lt; 0.05). Moreover, TA supplementation was capable to regulate the fecal microbiota diversity, manifesting in a linearly increased Chao1 index and observed species and a linearly decreased Pielou's index (P &lt; 0.05). The abundance of Lactobacillus reuteri, Lactobacillus amylovorus, Clostridium butyricum were increased, while the abundance of Prevotella copri was decreased, by treatment (P &lt; 0.05). Therefore, we speculated that TA supplementation would improve growth performance and reduce fecal ammonia emission through improving nutrient digestibility, which was attributed to the increase of jejunal villus height and the regulation of fecal microbiota