Odor-guided behaviors, including homing, predator avoidance, or food and mate searching, are ubiquitous in animals. It is only recently that the neural substrate underlying olfactomotor behaviors in vertebrates was uncovered in lampreys. It consists of a neural pathway extending from the medial part of the olfactory bulb (medOB) to locomotor control centers in the brainstem via a single relay in the caudal diencephalon. This hardwired olfactomotor pathway is present throughout life and may be responsible for the olfactory-induced motor behaviors seen at all life stages. We investigated modulatory mechanisms acting on this pathway by conducting anatomical (tract tracing and immunohistochemistry) and physiological (intracellular recordings and calcium imaging) experiments on lamprey brain preparations. We show that the GABAergic circuitry of the olfactory bulb (OB) acts as a gatekeeper of this hardwired sensorimotor pathway. We also demonstrate the presence of a novel olfactomotor pathway that originates in the non-medOB and consists of a projection to the lateral pallium (LPal) that, in turn, projects to the caudal diencephalon and to the mesencephalic locomotor region (MLR). Our results indicate that olfactory inputs can induce behavioral responses by activating brain locomotor centers via two distinct pathways that are strongly modulated by GABA in the OB. The existence of segregated olfactory subsystems in lampreys suggests that the organization of the olfactory system in functional clusters may be a common ancestral trait of vertebrates.

Lampreys, one of two living lineages of jawless vertebrates, are always intriguing for their feeding behavior via the toothed suctorial disc and life cycle comprising the ammocoete, metamorphic, and adult stages. However, they left a meager fossil record, and their evolutionary history remains elusive. Here we report two superbly preserved large lampreys from the Middle-Late Jurassic Yanliao Biota of North China and update the interpretations of the evolution of the feeding apparatus, the life cycle, and the historic biogeography of the group. These fossil lampreys' extensively toothed feeding apparatus differs radically from that of their Paleozoic kin but surprisingly resembles the Southern Hemisphere pouched lamprey, which foreshadows an ancestral flesh-eating habit for modern lampreys. Based on the revised petromyzontiform timetree, we argued that modern lampreys' three-staged life cycle might not be established until the Jurassic when they evolved enhanced feeding structures, increased body size and encountered more penetrable host groups. Our study also places modern lampreys' origin in the Southern Hemisphere of the Late Cretaceous, followed by an early Cenozoic anti-tropical disjunction in distribution, hence challenging the conventional wisdom of their biogeographical pattern arising from a post-Cretaceous origin in the Northern Hemisphere or the Pangean fragmentation in the Early Mesozoic.

Somatostatins (SSs) are a structurally diverse family of neuropeptides that play important roles in the regulation of growth, development and metabolism in vertebrates. It has been recently proposed that the common ancestor of gnathostomes possessed three SS genes, namely SS1, SS2 and SS5. SS1 and SS2 are still present in most extant gnathostome species investigated so far while SS5 primarily occurs in chondrichthyes, actinopterygians and actinistia but not in tetrapods. Very little is known about the repertoire of SSs in cyclostomes, which are extant jawless vertebrates. In the present study, we report the cloning of the cDNAs encoding three distinct lamprey SS variants that we call SSa, SSb and SSc. SSa and SSb correspond to the two SS variants previously characterized in lamprey, while SSc appears to be a totally novel one. SSa exhibits the same sequence as gnathostome SS1. SSb differs from SSa by only one substitution (Thr12→Ser). SSc exhibits a totally unique structure (ANCRMFYWKTMAAC) that shares only 50% identity with SSa and SSb. SSa, SSb and SSc precursors do not exhibit any appreciable sequence similarity outside the C-terminal region containing the SS sequence. Phylogenetic analyses failed to clearly assign orthology relationships between lamprey and gnathostome SS genes. Synteny analysis suggests that the SSc gene arose before the split of the three gnathostome genes SS1, SS2 and SS5.

Studies on the expression of cellular glycans are limited by a lack of sensitive tools that can discriminate specific structural features. Here we describe the development of a robust platform using immunized lampreys (Petromyzon marinus), which secrete variable lymphocyte receptors called VLRBs as antibodies, for generating libraries of anti-glycan reagents. We identified a wide variety of glycan-specific VLRBs detectable in lamprey plasma after immunization with whole fixed cells, tissue homogenates, and human milk. The cDNAs from lamprey lymphocytes were cloned into yeast surface display (YSD) libraries for enrichment by multiple methods. We generated VLRB-Ig chimeras, termed smart anti-glycan reagents (SAGRs), whose specificities were defined by microarray analysis and immunohistochemistry. 15 VLRB antibodies were discovered that discriminated between linkages, functional groups and unique presentations of the terminal glycan motif. The development of SAGRs will enhance future studies on glycan expression by providing sequenced, defined antibodies for a variety of research applications.

Tectoreticular (TR) cells along the diencephalic-mesencephalic border are the origin of prominent crossed and uncrossed pathways that project to the middle (MRRN) and posterior (PRRN) rhombencephalic reticular nuclei in juvenile and adult lampreys [I.C. Zompa, R. Dubuc, Diencephalic and mesencephalic projections to rhombencephalic reticular nuclei in lampreys, Brain Res. (1998) in press.]. This study investigated the synaptic contacts between TR axons and the reticular cells. Intracellular recordings were carried out in reticular neurones (n=124) while microstimulating the TR regions. Tectoreticular inputs were recorded in all reticular cells studied (248 PSPs); although stronger responses were evoked in the MRRN neurones. The majority of responses were excitatory, but increasingly mixed and inhibitory when recorded in the middle and caudal part of the reticular nuclei. The excitation had the shortest onset latencies and sharpest slopes measured in both reticular nuclei, while the inhibition was longer and smoother. The characteristics of TR inputs to different reticular cell types is also presented. The transmission of evoked responses was isolated to the crossed and uncrossed TR pathways by studying the effects of 1% Xylocaine ejections and surgical lesions. The TR inputs were transmitted to reticular cells through monosynaptic and polysynaptic contacts. The synaptic transmission involved excitatory amino acids, acting through AMPA and NMDA receptors, while the inhibition was glycinergic. Comparisons with other sensory systems in lampreys are discussed.

Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine-rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomplete germline VLRA and VLRB genes. Here we show that in sea lampreys (Petromyzon marinus) VLRA and VLRB anticipatory receptors are expressed by separate lymphocyte populations by monoallelic VLRA or VLRB assembly, together with expression of cytosine deaminase 1 (CDA1) or 2 (CDA2), respectively. Distinctive gene expression profiles for VLRA(+) and VLRB(+) lymphocytes resemble those of mammalian T and B cells. Although both the VLRA and the VLRB cells proliferate in response to antigenic stimulation, only the VLRB lymphocytes bind native antigens and differentiate into VLR antibody-secreting cells. Conversely, VLRA lymphocytes respond preferentially to a classical T-cell mitogen and upregulate the expression of the pro-inflammatory cytokine genes interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF). The finding of T-like and B-like lymphocytes in lampreys offers new insight into the evolution of adaptive immunity.

Ice ages are known to be the most dominant palaeoclimatic feature occurring on Earth, producing severe climatic oscillations and consequently shaping the distribution and the population structure of several species. Lampreys constitute excellent models to study the colonization of freshwater systems, as they commonly appear in pairs of closely related species of anadromous versus freshwater resident adults, thus having the ability to colonize new habitats, through the anadromous species, and establish freshwater resident derivates. We used 10 microsatellite loci to investigate the spatial structure, patterns of gene flow and migration routes of Lampetra populations in Europe. We sampled 11 populations including the migratory L. fluviatilis and four resident species, L. planeri, L. alavariensis, L. auremensis and L. lusitanica, the last three endemic to the Iberian Peninsula. In this southern glacial refugium almost all sampled populations represent a distinct genetic cluster, showing high levels of allopatric differentiation, reflecting long periods of isolation. As result of their more recent common ancestor, populations from northern Europe are less divergent among them, they are represented by fewer genetic clusters, and there is evidence of strong recent gene flow among populations. These previously glaciated areas from northern Europe may have been colonized from lampreys expanding out of the Iberian refugia. The pair L. fluviatilis/L. planeri is apparently at different stages of speciation in different locations, showing evidences of high reproductive isolation in the southern refugium, and low differentiation in the north.

In lampreys, respiration consists of a fast and a slow rhythm. This study was aimed at characterizing both anatomically and physiologically the brainstem regions involved in generating the two rhythms. The fast rhythm generator has been located by us and others in the rostral hindbrain, rostro-lateral to the trigeminal motor nucleus. More recently, this was challenged by researchers reporting that the fast rhythm generator was located more rostrally and dorsomedially, in a region corresponding to the mesencephalic locomotor region. These contradictory observations made us re-examine the location of the fast rhythm generator using anatomical lesions and physiological recordings. We now confirm that the fast respiratory rhythm generator is in the rostro-lateral hindbrain as originally described. The slow rhythm generator has received less attention. Previous studies suggested that it was composed of bilateral, interconnected rhythm generating regions located in the caudal hindbrain, with ascending projections to the fast rhythm generator. We used anatomical and physiological approaches to locate neurons that could be part of this slow rhythm generator. Combinations of unilateral injections of anatomical tracers, one in the fast rhythm generator area and another in the lateral tegmentum of the caudal hindbrain, were performed to label candidate neurons on the non-injected side of the lateral tegmentum. We found a population of neurons extending from the facial to the caudal vagal motor nuclei, with no clear clustering in the cell distribution. We examined the effects of stimulating different portions of the labeled population on the respiratory activity. The rostro-caudal extent of the population was arbitrarily divided in three portions that were each stimulated electrically or chemically. Stimulation of either of the three sites triggered bursts of discharge characteristic of the slow rhythm, whereas inactivating any of them stopped the slow rhythm. Substance P injected locally in the lateral tegmentum accelerated the slow respiratory rhythm in a caudal hindbrain preparation. Our results show that the fast respiratory rhythm generator consists mostly of a population of neurons rostro-lateral to the trigeminal motor nucleus, whereas the slow rhythm generator is distributed in the lateral tegmentum of the caudal hindbrain.

There is controversy about whether axotomized neurons undergo death or only severe atrophy after spinal cord injury (SCI) in mammals. Lampreys recover from complete spinal transection, but only about half of the severed spinal-projecting axons regenerate through the site of injury. The fates of the unregenerated neurons remain unknown, and until now death of axotomized spinal-projecting neurons has not been described in the lamprey brain. We now report that in animals allowed to survive for 12 or more weeks after spinal cord transection, several identified reticulospinal (RS) neurons were missing in Nissl-stained or neurofilament-immunostained brain whole mounts. At earlier times, these neurons were swollen and pale in Nissl-stained preparations. Retrograde fluorescent labeling from the site of transection combined with TUNEL histochemistry suggested that neuronal death, including that of the identified RS neurons, began in animals 4 weeks posttransection, reaching a peak at 12-16 weeks. This was not seen in untransected animals. The TUNEL positivity suggests that some cells were dying by apoptosis. Of special interest, among the identified neurons, this delayed cell death was restricted to neurons that at earlier posttransection times have a low probability of regeneration. These data show that SCI induces delayed cell death in lamprey spinal-projecting neurons and suggest that the reason why some neurons are "bad regenerators" is that they are already undergoing apoptotic cell death. Thus protection from apoptosis may be necessary in order to enhance axonal regeneration after SCI.

Foxg1 is a key regulator of the early development of the vertebrate forebrain and sensory organs. In this study, we describe for the first time three foxg1 paralogues in lamprey, representative of one of two basally diverged lineages of vertebrates-the agnathans. We also first describe three foxg1 genes in sterlet-representative of one of the evolutionarily ancient clades of gnathostomes. According to the analysis of local genomic synteny, three foxg1 genes of agnathans and gnathostomes have a common origin as a result of two rounds of genomic duplications in the early evolution of vertebrates. At the same time, it is difficult to reliably establish pairwise orthology between foxg1 genes of agnathans and gnathostomes based on the analysis of phylogeny and local genomic synteny, as well as our studies of the spatiotemporal expression of foxg1 genes in the river lamprey Lampetra fluviatilis and the sterlet Acipenser ruthenus. Thus, the appearance of three foxg1 paralogues in agnathans and gnathostomes could have occurred either as a result of two rounds of duplication of the vertebrate common ancestor genome (2R hypothesis) or as a result of the first common round followed by subsequent independent polyploidizations in two evolutionary lineages (1R hypothesis).

Detection of chemical cues is important to guide locomotion in association with feeding and sexual behavior. Two neural pathways responsible for odor-evoked locomotion have been characterized in the sea lamprey (Petromyzon marinus L.), a basal vertebrate. There is a medial pathway originating in the medial olfactory bulb (OB) and a lateral pathway originating from the rest of the OB. These olfactomotor pathways are present throughout the life cycle of lampreys, but olfactory-driven behaviors differ according to the developmental stage. Among possible mechanisms, dopaminergic (DA) modulation in the OB might explain the behavioral changes. Here, we examined DA modulation of olfactory transmission in lampreys. Immunofluorescence against DA revealed immunoreactivity in the OB that was denser in the medial part (medOB), where processes were observed close to primary olfactory afferents and projection neurons. Dopaminergic neurons labeled by tracer injections in the medOB were located in the OB, the posterior tuberculum, and the dorsal hypothalamic nucleus, suggesting the presence of both intrinsic and extrinsic DA innervation. Electrical stimulation of the olfactory nerve in an in vitro whole-brain preparation elicited synaptic responses in reticulospinal cells that were modulated by DA. Local injection of DA agonists in the medOB decreased the reticulospinal cell responses whereas the D2 receptor antagonist raclopride increased the response amplitude. These observations suggest that DA in the medOB could modulate odor-evoked locomotion. Altogether, these results show the presence of a DA innervation within the medOB that may play a role in modulating olfactory inputs to the motor command system of lampreys.

The lamprey represents the oldest group of living vertebrates and has been a key organism in various research fields such as evolutionary developmental biology and neuroscience. However, no knock-in technique for this animal has been established yet, preventing application of advanced genetic techniques. Here, we report efficient generation of F0 knock-in lampreys by CRISPR-Cas9-mediated genome editing. A donor plasmid containing a heat-shock promoter was co-injected with a short guide RNA (sgRNA) for genome digestion, a sgRNA for donor plasmid digestion, and Cas9 mRNA. Targeting different genetic loci, we succeeded in generating knock-in lampreys expressing photoconvertible protein Dendra2 as well as those expressing EGFP. With its simplicity, design flexibility, and high efficiency, we propose that the present method has great versatility for various experimental uses in lamprey research and that it can also be applied to other "non-model" organisms.

The parasitic sea lamprey (Petromyzon marinus) has caused extensive losses to commercial fish stocks of the upper Great Lakes of North America. Methods of controlling the sea lamprey include trapping, barriers to prevent migration, and use of a chemical lampricide (3-trifluoromethyl-4-nitrophenol) to kill the filter-feeding larvae. Concerns about the non-specificity of these methods have prompted continued development of species-specific methods to control lampreys outside their native range. In this study, we considered the utility of RNA interference to develop a sea lamprey-specific lampricide. Injection of six different short interfering, double-stranded RNAs (siRNAs) into lamprey embryos first confirmed that the siRNAs could reduce the targeted transcript levels by more than 50%. Two size classes of lamprey larvae were then fed the siRNAs complexed with liposomes, and three of the siRNAs (targeting elongation factor 1α, calmodulin, and α-actinin) reduced transcript levels 2.5, 3.6, and 5.0-fold, respectively, within the lamprey midsections. This is not only the first demonstration of RNAi in lampreys, but it is also the first example of delivery of siRNAs to a non-mammalian vertebrate through feeding formulations. One of the siRNA treatments also caused increased mortality of the larvae following a single feeding of siRNAs, which suggests that prolonged or multiple feedings of siRNAs could be used to kill filter-feeding larvae within streams, following development of a slow-release formulation. The genes targeted in this study are highly conserved across many species, and only serve as a proof-of-concept demonstration that siRNAs can be used in lampreys. Given that RNA interference is a sequence-specific phenomenon, it should be possible to design siRNAs that selectively target gene sequences that are unique to sea lampreys, and thus develop a technology to control these pests without adversely affecting non-target species.

Sea lampreys (Petromyzon marinus) are basal vertebrates that exhibit reproductive control via a hypothalamic-pituitary-gonadal axis. The function and evolution of the hypothalamic and pituitary peptide hormones are well studied in this species, whereas the functions of classical sex steroid hormones have not been well established due to their low or non-detectable plasma levels. Sea lamprey pheromone 3-keto petromyzonol sulfate (3kPZS) has been shown to increase while 3-keto allocholic acid (3kACA) decreases plasma 15α-hydroxyprogesterone (15αP) levels in prespermiating males (PSM) but not in preovulatory females (POF). However, spermiating male washings that contain both 3kPZS and 3kACA facilitate spawning in both sexes. Therefore, we wondered if the effects of pheromones on POF were elicited by classical steroid hormones such as progesterone, androstenedione, testosterone and estradiol. We hypothesized that waterborne 3kACA and 3kPZS differentially alter steroid hormone levels in prespawning sea lampreys. We determined the sex differences and pheromonal effects on steroid hormone levels in prespawning sea lampreys using sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods. Some PSM became spermiating (SM) at the time of sample collection, and those data were treated as a separate group. We found that males contained more androstenedione and progesterone in the gonad and more estradiol and testosterone in the plasma than POF, whereas POF contained more gonadal testosterone than males (no detectable gonadal testosterone). In POF, 3kPZS decreased gonadal androstenedione but increased gonadal progesterone and plasma estradiol, whereas 3kACA only increased gonadal progesterone levels. Exposure to 3kPZS for 4 h increased plasma 15αP in POF and SM, and gonadal 15αP in POF. Interestingly, 3kACA or 3kPZS depleted gonadal or plasma 15αP in PSM at various time points. On the other hand, both pheromones had no significant effect on androstenedione, progesterone or estradiol levels in males. Plasma testosterone levels did not change after pheromone exposure in both sexes. We conclude that sea lamprey pheromones 3kACA and 3kPZS induced differential steroidal responses in POF, PSM and SM.

Cathepsin D (EC 3.4.23.5) is a lysosomal aspartic proteinase of the pepsin superfamily which participates in various digestive processes within the cell. In the present study, the full length cDNA of a novel cathepsin D homologue was cloned from the buccal glands of lampreys (Lampetra japonica) for the first time, including a 124-bp 5' terminal untranslated region (5'-UTR), a 1194-bp open reading frame encoding 397 amino acids, and a 472-bp 3'-UTR. Lamprey cathepsin D is composed of a signal peptide (Met 1-Ala 20), a propeptide domain (Leu 21-Ala 48) and a mature domain (Glu 76-Val 397), and has a conserved bilobal structure. Cathepsin D was widely distributed in the buccal glands, immune bodies, hearts, intestines, kidneys, livers, and gills of lampreys. After challenging with Escherichia coli or Staphylococcus aureus, the expression level of lamprey cathepsin D in the buccal gland was 8.5-fold or 6.5-fold higher than that in the PBS group. In addition, lamprey cathepsin D stimulated with Escherichia coli was also up-regulated in the hearts, kidneys, and intestines. As for the Staphylococcus aureus challenged group, the expression level of lamprey cathepsin D was found increased in the intestines. The above results revealed that lamprey cathepsin D may play key roles in immune response to exogenous pathogen and could serve as a potential antibacterial agent in the near future. In addition, lamprey cathepsin D was subcloned into pcDNA 3.1 vector and expressed in the human embryonic kidney 293 cells. The recombinant lamprey cathepsin D could degrade hemoglobin, fibrinogen, and serum albumin which are the major components in the blood, suggested that lamprey cathepsin D may also act as a digestive enzyme during the adaptation to a blood-feeding lifestyle.

Axon regeneration is critical for restoring neural function after spinal cord injury. This has prompted a series of studies on the neural and functional recovery of lampreys after spinal cord transection. Despite this, there are still many basic questions remaining about how much functional recovery depends on axon regeneration. Our goal was to examine how swimming performance is related to degree of axon regeneration in lampreys recovering from spinal cord transection by quantifying the relationship between swimming performance and percent axon regeneration of transected lampreys after 11 weeks of recovery. We found that while swimming speeds varied, they did not relate to percent axon regeneration. In fact, swimming speeds were highly variable within individuals, meaning that most individuals could swim at both moderate and slow speeds, regardless of percent axon regeneration. However, none of the transected individuals were able to swim as fast as the control lampreys. To swim fast, control lampreys generated high amplitude body waves with long wavelengths. Transected lampreys generated body waves with lower amplitude and shorter wavelengths than controls, and to compensate, transected lampreys increased their wave frequencies to swim faster. As a result, transected lampreys had significantly higher frequencies than control lampreys at comparable swimming velocities. These data suggest that the control lampreys swam more efficiently than transected lampreys. In conclusion, there appears to be a minimal recovery threshold in terms of percent axon regeneration required for lampreys to be capable of swimming; however, there also seems to be a limit to how much they can behaviorally recover.

Muscle tissues contain the most classic sarcomeric myosin, called myosin II, which consists of 2 heavy chains (MYHs) and 4 light chains. In the case of humans (tetrapod), a total of 6 fast skeletal-type MYH genes (MYHs) are clustered on a single chromosome. In contrast, torafugu (teleost) contains at least 13 fast skeletal MYHs, which are distributed in 5 genomic regions; the MYHs are clustered in 3 of these regions. In the present study, the evolutionary relationship among fast skeletal MYHs is elucidated by comparing the MYHs of teleosts and tetrapods with those of cyclostome lampreys, one of two groups of extant jawless vertebrates (agnathans). We found that lampreys contain at least 3 fast skeletal MYHs, which are clustered in a head-to-tail manner in a single genomic region. Although there was apparent synteny in the corresponding MYH cluster regions between lampreys and tetrapods, phylogenetic analysis indicated that lamprey and tetrapod MYHs have independently duplicated and diversified. Subsequent transgenic approaches showed that the 5'-flanking sequences of Japanese lamprey fast skeletal MYHs function as a regulatory sequence to drive specific reporter gene expression in the fast skeletal muscle of zebrafish embryos. Although zebrafish MYH promoters showed apparent activity to direct reporter gene expression in myogenic cells derived from mice, promoters from Japanese lamprey MYHs had no activity. These results suggest that the muscle-specific regulatory mechanisms are partially conserved between teleosts and tetrapods but not between cyclostomes and tetrapods, despite the conserved synteny.

Lampreys are suitable animal models for studying the evolution of the vertebrate nervous system because they belong to the earliest group of extant vertebrates, the agnathans. The general organization of the serotonergic central nervous system is well known in lampreys, but information about its peripheral organization is lacking. In the present study, high-performance liquid chromatography and immunohistochemistry with an antibody against serotonin were used to study the presence and peripheral distribution of serotonergic elements in the head of larval sea lampreys. Adult lampreys were also analyzed in order to compare the organization of the system in larval and postmetamorphic stages. Serotonergic cells were observed in the cranial nerve ganglia, the musculature, the taste buds, and in the gills. Serotonergic fibers were extensive in all tissues except the epidermis. Possible roles were proposed for the different cell types observed in relation to their location, structure, and innervation patterns. The serotonergic cells appear to be involved in the oxygen and taste chemoreception processes, the modulation of musculature contraction, and in the regulation of cilia beat frequency and mucus secretion in lampreys. The extensive presence of serotonergic elements in the peripheral nervous system of lampreys suggests a close relationship with the organization of this system in invertebrate groups.

Previous studies have shown that lamprey buccal glands contain some regulators related to anticoagulation, nociception, and immune responses due to the blood sucking habit. Regrettably, the protein expression profile in the buccal glands of feeding lampreys has never been reported yet. The present study was performed in order to further identify more proteins which are closely associated with lamprey feeding process.

Horizontal gene transfer (HGT) has been recognized to be an important mechanism that shaped the evolution and genomes of prokaryotes and unicellular eukaryotes. However, HGT is regarded to be exceedingly rare among eukaryotes. We discovered massive transfers of a DNA transposon, a Tc1 element encoding a transposase, between multiple teleost fishes and lampreys that last shared a common ancestor over 500 Ma. Members of this group of Tc1 elements were found to exhibit a mosaic phylogenetic distribution, yet their sequences were highly similar even between distantly related lineages (95%-99% identity). Our molecular phylogenetic analyses suggested that horizontal transfers of this element happened repeatedly, involving multiple teleost fishes that are phylogenetically only distantly related. Interestingly, almost all the affected teleost lineages are also known to be subject to lamprey parasitism, suggesting that the horizontal transfers between vertebrates might have occurred through parasite-host interaction. The genomes of several northern hemisphere lamprey species, including that of the sea lamprey (Petromyzon marinus), were found to contain thousands of copies of the foreign elements. Impact of this event is discussed in relation to other peculiar genomic features of lampreys.