The origin of whales and their transition from terrestrial life to a fully aquatic existence has been studied in depth. Palaeontological, morphological and molecular studies suggest that the order Cetacea (whales, dolphins and porpoises) is more closely related to the order Artiodactyla (even-toed ungulates, including cows, camels and pigs) than to other ungulate orders. The traditional view that the order Artiodactyla is monophyletic has been challenged by molecular analyses of variations in mitochondrial and nuclear DNA. We have characterized two families of short interspersed elements (SINEs) that were present exclusively in the genomes of whales, ruminants and hippopotamuses, but not in those of camels and pigs. We made an extensive survey of retropositional events that might have occurred during the divergence of whales and even-toed ungulates. We have characterized nine retropositional events of a SINE unit, each of which provides phylogenetic resolution of the relationships among whales, ruminants, hippopotamuses and pigs. Our data provide evidence that whales, ruminants and hippopotamuses form a monophyletic group.

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Short interspersed repetitive elements (SINEs) are a type of retroposon, being members of a class of informational molecules that are amplified via cDNA intermediates and flow back into the host genome. In contrast to retroviruses and retrotransposons, SINEs do not encode the enzymes required for their amplification, such as reverse transcriptases, so they are presumed to borrow these enzymes from other sources. In the present study, we isolated a family of long interspersed repetitive elements (LINEs) from the turtle genome. The sequence of this family was found to be very similar to those of the avian CR1 family. To our surprise, the sequence at the 3 end of the LINE in the turtle genome was nearly identical to that of a family of tortoise SINEs. Since CR1-like LINEs are widespread in birds and in many other reptiles, including the turtle, and since the tortoise SINEs are only found in vertical-necked turtles, it seems possible that the sequence at the 3 end of the tortoise SINEs might have been generated by recombination with the CR1-like LINE in a common ancestor of vertical-necked turtles, after the divergence of side-necked turtles. We extended our observations to show that the 3-end sequences of families of several tRNA-derived SINEs, such as the salmonid HpaI family, the tobacco TS family, and the salmon SmaI family, might have originated from the respective LINEs. Since it appears reasonable that the recognition sites of LINEs for reverse transcriptase are located within their 3-end sequences, these results provide the basis for a general scheme for the mechanism by which SINEs might acquire retropositional activity. We propose here that tRNA-derived SINEs might have been generated by a recombination event in which a strong-stop DNA with a primer tRNA, which is an intermediate in the replication of certain retroviruses and long terminal repeat retrotransposons, was directly integrated at the 3 end of a LINE.The reverse flow of genetic information from RNA back into DNA is known as retroposition, and each transposed informational element is known as a retroposon (23,36). Highly repetitive elements in eukaryotic genomes (28, 29), such as short interspersed repetitive elements (SINEs), long interspersed repetitive elements (LINEs), and processed retropseudogenes, are all included in this category. Retroposition appears to be a major evolutionary force that has contributed to the maintenance of the remarkable fluidity of eukaryotic genomes (28,36).

Many SINEs and LINEs have been characterized to date, and examples of the SINE and LINE pair that have the same 3′ end sequence have also increased. We report the phylogenetic relationships of nearly all known LINEs from which SINEs are derived, including a new example of a SINE/LINE pair identified in the salmon genome. We also use several biological examples to discuss the impact and significance of SINEs and LINEs in the evolution of vertebrate genomes.

We have identified a new superfamily of vertebrate short interspersed repetitive elements (SINEs), designated V-SINEs, that are widespread in fishes and frogs. Each V-SINE includes a central conserved domain preceded by a 5Ј-end tRNA-related region and followed by a potentially recombinogenic (TG) n tract, with a 3Ј tail derived from the 3Ј untranslated region (UTR) of the corresponding partner long interspersed repetitive element (LINE) that encodes a functional reverse transcriptase. The central domain is strongly conserved and is even found in SINEs in the lamprey genome, suggesting that V-SINEs might be ∼550 Myr old or older in view of the timing of divergence of the lamprey lineage from the bony fish lineage. The central conserved domain might have been subject to some form of positive selection. Although the contemporary 3Ј tails of V-SINEs differ from one another, it is possible that the original 3Ј tail might have been replaced, via recombination, by the 3Ј tails of more active partner LINEs, thereby retaining retropositional activity and the ability to survive for long periods on the evolutionary time scale. It seems plausible that V-SINEs may have some function(s) that have been maintained by the coevolution of SINEs and LINEs during the evolution of vertebrates.[The sequences reported in this paper have been deposited in the DDBJ/GenBank database under accession nos. AB072981-AB073004. Supplemental figures are available online at http://www.genome.org.]Retroposons are genetic elements that have moved within and among genomes via an RNA intermediate (Weiner et al. 1986). They include SINEs, LINEs, LTR-retrotransposons, and retroviruses. L1 and Alu are representative of the LINEs and SINEs, respectively, in the human genome (Weiner et al. 1986;Eickbush 1994;Smit 1996). An analysis of the entire human genome revealed that retroposons constitute up to 40% of the genome and that protein-coding sequences account for only about 1.5% (International Human Genome Sequencing Consortium 2001). The above mentioned 40% of the human genome includes several clearly discernible groups of retroposons, such as L1, LINE2, Alu, and MIR, and these easily recognizable sequences represent the results of relatively recent amplifications over the past 200 Myr (International Human Genome Sequencing Consortium 2001). Accordingly, the proportion of the genome that originated from retroposons may increase up to as much as 60% to 70%, if we could identify and include ancient retroposons, which might have been amplified in the very distant past, are now barely recognizable as such, and are buried in the genome as debris. Such a putative extensive contribution of retroposons to the construction of the contemporary human genome has not been anticipated.Typical SINEs vary from 100 to 500 bp in length. They have an internal RNA polymerase III (pol III) promoter but no open reading frames (Okada 1991;Schmid and Maraia 1992;Deininger and Batzer 1993;Okada and Ohshima 1995;Schmid 1998). Many families of SINEs have been identified in multic...

Wnt signaling has diverse actions in cardiovascular development and disease processes. Secreted frizzled-related protein 5 (Sfrp5) has been shown to function as an extracellular inhibitor of non-canonical Wnt signaling that is expressed at relatively high levels in white adipose tissue. The aim of this study was to investigate the role of Sfrp5 in the heart under ischemic stress. Sfrp5 KO and WT mice were subjected to ischemia/reperfusion (I/R). Although Sfrp5-KO mice exhibited no detectable phenotype when compared with WT control at baseline, they displayed larger infarct sizes, enhanced cardiac myocyte apoptosis, and diminished cardiac function following I/R. The ischemic lesions of Sfrp5-KO mice had greater infiltration of Wnt5a-positive macrophages and greater inflammatory cytokine and chemokine gene expression when compared with WT mice. In bone marrow-derived macrophages, Wnt5a promoted JNK activation and increased inflammatory gene expression, whereas treatment with Sfrp5 blocked these effects. These results indicate that Sfrp5 functions to antagonize inflammatory responses after I/R in the heart, possibly through a mechanism involving non-canonical Wnt5a/JNK signaling.Inflammation is widely recognized to be involved in the pathogenesis, severity, and outcome of ischemic heart disease (1). Obesity is thought to contribute to cardiovascular disorders, at least in part, through the systemic release of pro-inflammatory adipokines by dysfunctional white adipose tissue (WAT) 2 (2, 3). Inflammation has complex roles in both adaptive healing process following infarction as well as in the maladaptive processes that contribute to heart failure (4 -7), and the acute healing and eventual outcome of ischemic myocardial injury are dependent upon the appropriately choreographed regulation of numerous pro-and anti-inflammatory modulators. In this regard, immune modulators produced by adipose tissue can either facilitate or impair the myocardial healing process, depending on the status of adipose tissue function and the composition of its inflammatory secretome (3,8,9). Thus, a better understanding of the links between obesity-mediated inflammatory processes and post-infarct remodeling of the heart is warranted.At the cellular level, inflammatory processes are tightly orchestrated by secreted signaling molecules that bind to specific cell surface receptors and activate intracellular signaling pathways. Signaling by Wnt ligands is a major regulator of several biological processes, but its roles in modulating inflammatory responses are relatively understudied. The 19 Wnt family proteins contain cysteine-rich domains and activate signaling by binding to one or more of the 10 frizzled family receptors (10). Wnt signaling can be classified as canonical or a noncanonical (10, 11). Canonical Wnt signaling involves activation of the ␤-catenin signaling pathway. Non-canonical Wnt signaling involves other pathways including planar cell polarity and Ca 2ϩ pathways (10, 12, 13). Wnt3a is the prototypical ligand that induces canonica...

Whole-genome screening indicates a possible burst of formation of processed pseudogenes and Alu repeats by particular L1 subfamilies in ancestral primates Abundant pseudogenes are a feature of mammalian genomes. Processed pseudogenes (PPs) are reverse transcribed from mRNAs. Recent molecular biological studies show that mammalian long interspersed element 1 (L1)-encoded proteins may have been involved in PP reverse transcription. Here, we present the first comprehensive analysis of human PPs using all known human genes as queries. AbstractBackground: Abundant pseudogenes are a feature of mammalian genomes. Processed pseudogenes (PPs) are reverse transcribed from mRNAs. Recent molecular biological studies show that mammalian long interspersed element 1 (L1)-encoded proteins may have been involved in PP reverse transcription. Here, we present the first comprehensive analysis of human PPs using all known human genes as queries.

We have characterized a family of tRNAderived short interspersed repetitive elements (SINEs) in the tobacco genome. Members of this family of SINEs, designated TS, have a composite structure and include a region structurally similar to a rabbit tRNALYS, a tRNA-unrelated region, and a TTG repeat of variable length at the 3' end. Southern blot hybridization, together with a search of the GenBank data base, showed that various plants belonging to the families Solanaceae and Convolvulaceae contain sequences homologous to the TS family in the introns and flanking regions of many genes, whereasArabidopsis in the family Cruciferae and several species of monocotyledonous plants do not. The TS family is widely involved in structural and genetic variations in the genomes ofmany plants that belong to the order Tubiflorae. All of nine sequences identified in a data base search are truncated at their 5' regions and lack the tRNA-related region of the TS family. We characterized the entire sequence of the members of the TS family and found that this family can be categorized as a member of a group ofSINEs with a tRNALys-like structure, as can several animal SINEs. The TS family can be divided into two major subfamilies by analysis of diagnostic positions, and one of the subfamilies is clearly younger than the other. Amplification ofmany copies ofthe full sequence of the younger subfamily occurred during the recent evolution of the tobacco lineage. We also discuss mechanisms that could be involved in the generation of SINEs in animals and also in plants.