Current Biology, Vol. 15, 185–191, January 26, 2005, ©2005 Elsevier Ltd All rights reserved. DOI 10.1016/j.cub.2005 . 0 1 .003A Phylogenomic Inventory of Meiotic Genes:Evidence for Sex in Giardiaand an Early Eukaryotic Origin of Meiosishomologs of well-known meiotic genes. The direct impli-cations are that Giardia is, or was recently, capable ofsexual reproduction and, thus, does not represent anancient eukaryotic lineage that diverged before meiosisarose. Instead, the origin of meiosis predates the diver-Marilee A. Ramesh,2,3,4Shehre-Banoo Malik,1,3,4and John M. Logsdon, Jr.1,4,*1Department of Biological SciencesRoy J. Carver Center for Comparative GenomicsUniversity of IowaIowa City, Iowa 52242 gence of Giardia in eukaryotic evolution.In defining a “core meiotic recombination machinery”2Department of BiologyRoanoke College and providing the first extensive review of meiotic genesin an explicitly comparative context, Villeneuve and Hill-Salem, Virginia 24153ers [2] recently argued that “the very essence of sex ismeiotic recombination.” Molecular mechanisms of mei-osis are being elucidated from diverse eukaryotic modelSummarysystems, providing insight into the origin and evolutionof eukaryotic sex through conserved meiotic compo-Sexual reproduction in eukaryotes is accomplished bymeiosis, a complex and specialized process of cell nents. However, such systematic genetic and/or geno-mic approaches have only been applied to a phylogenet-division that results in haploid cells (e.g., gametes).The stereotypical reductive division in meiosis is a ically-restricted set of eukaryotes—animals, fungi, andplants (herein, AFP)—precluding protists with only scantmajor evolutionary innovation in eukaryotic cells [1],and delineating its history is key to understanding the information on meiosis [8]. Phylogenetic analyses ofrRNA and proteins show that eukaryotic diversity isevolution of sex [2]. Meiosis arose early in eukaryoticevolution, but when and how meiosis arose and largely represented by protists [6, 9–12], and a compre-hensive comparative analysis of meiosis must considerwhether all eukaryotes have meiosis remain openquestions [3]. The known phylogenetic distribution of protists [13] to determine if meiosis is universal amongeukaryotes. Protists reveal evidence of both evolution-meiosis comprises plants, animals, fungi, and numer-ous protists [4]. Diplomonads including Giardia intesti- ary conservation and variation in the meiotic machinery;both unconventional meiosis and no meiosis have beennalis (syn. G. lamblia) are not known to have a sexualcycle [5]; these protists may be an early-diverging lin- reported among protists [14]. Indeed, sexuality is vari-ant—even deviant—among the protists [8, 15]; whethereage [6] and could represent a premeiotic stage ineukaryotic evolution. We surveyed the ongoing G. in- they possess meiotic machinery homologous to that inAFP is unknown because underlying molecular mecha-testinalis genome project data [7] and have identified,verified, and analyzed a core set of putative meiotic nisms have generally not been determined because ofthe lack of genetic tools. Recent protist genome se-genes—including five meiosis-specific genes—thatare widely present among sexual eukaryotes. The quencing projects have allowed access to such geneticdata, making comparative genomic studies feasible.presence of these genes indicates that: (1) Giardia iscapable of meiosis and, thus, sexual reproduction, (2) Among known meiotic genes, a list of genes central tomeiosis can be compiled and used to identify homologsthe evolution of meiosis occurred early in eukaryoticevolution, and (3) the conserved meiotic machinery of these genes in a more diverse set of eukaryotes,including the earliest branches on the eukaryotic treecomprises a large set of genes that encode a varietyof component proteins, including those involved in of life [13]. Cavalier-Smith [3] recently offered a synopsisof the origin of meiotic recombination machinery withmeiotic recombination.available, albeit limited, information.A genome project for G. intestinalis is nearly completeResults and Discussion[7, 16]. This pathogen causes giardiasis, a diarrheal dis-ease contracted in mammalian hosts by ingesting con-Eukaryotic Evolution and Meiotic Originstaminated water [5]. Phylogenetic analyses of SSU rRNAOur central goal was to determine whether genes encod-and of other genes indicate that diplomonads are amonging meiotic proteins were present in Giardia, both asthe deepest divergences in the eukaryotic lineage [17–indicators of Giardia’s potential to undergo meiosis and19]. Trees from different genes have not always placedsexual reproduction and as markers for the evolution ofGiardia on the deepest branch, but they generally putmeiosis itself. We have taken an inventory of GiardiaGiardia among the most early-diverging eukaryotes [20,genes that are clear homologs of genes with known21]. The deep placement of diplomonads depends onroles in meiosis in other eukaryotes. Considering Giardiathe root position, and most analyses employ a prokary-as an exemplar protist, a more complete picture of theotic outgroup root. Recent analyses that define the rootphylogenetic distribution of both meiotic genes, andby gene fusions suggest that a grouping of animals,thus meiosis itself, emerges. Giardia has unambiguousfungi, and some amoebae may represent the deepesteukaryotic split, with plants and most protists (including*Correspondence: [email protected]) placed on the other side of this ur-divide [22,3These authors contributed equally to this work.23]. If true, comparisons between AFP would be largely4The research for this report was begun in the Department of Biologyat Emory University, Atlanta, Georgia 30322.sufficient to diagnose the generalities and ancestralCurrent Biology186states, including the presence of meiosis, early in eukary- comprised of Spo11, Rad50/Mre11, Dmc1, Rad51,Msh4/Msh5, and Mlh1. We expanded a list of “core mei-otic evolution. Although this scenario is possible [12],current evidence is simply not sufficient to preclude otic genes” by including additional single genes andmeiotic members of multigene families. The addedGiardia from among the earliest diverging lineages ofeukaryotes; recent multigene analyses support diplomo- genes encode a synaptonemal complex protein (Hop1),recombination proteins (Hop2, Mnd1, and Rad52), andnads with parabasalids (together, two