{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:26:55Z","timestamp":1781105215719,"version":"3.54.1"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,4,30]]},"abstract":"<jats:p>\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    is a ubiquitous protozoan parasite capable of infecting all warm-blooded animals, including humans. Its closest extant relative,\n                    <jats:italic>Hammondia hammondi,<\/jats:italic>\n                    has never been found to infect humans and, in contrast to\n                    <jats:italic>T. gondii<\/jats:italic>\n                    , is highly attenuated in mice. To better understand the genetic bases for these phenotypic differences, we sequenced the genome of a\n                    <jats:italic>H. hammondi<\/jats:italic>\n                    isolate (HhCatGer041) and found the genomic synteny between\n                    <jats:italic>H. hammondi<\/jats:italic>\n                    and\n                    <jats:italic>T. gondii<\/jats:italic>\n                    to be &gt;95%. We used this genome to determine the\n                    <jats:italic>H. hammondi<\/jats:italic>\n                    primary sequence of two major\n                    <jats:italic>T. gondii<\/jats:italic>\n                    mouse virulence genes,\n                    <jats:italic>TgROP5<\/jats:italic>\n                    and\n                    <jats:italic>TgROP18<\/jats:italic>\n                    . When we expressed these genes in\n                    <jats:italic>T. gondii<\/jats:italic>\n                    , we found that\n                    <jats:italic>H. hammondi<\/jats:italic>\n                    orthologs of TgROP5 and TgROP18 were functional. Similar to\n                    <jats:italic>T. gondii<\/jats:italic>\n                    , the\n                    <jats:italic>HhROP5<\/jats:italic>\n                    locus is expanded, and two distinct HhROP5 paralogs increased the virulence of a\n                    <jats:italic>T. gondii TgROP5<\/jats:italic>\n                    knockout strain. We also identified a 107 base pair promoter region, absent only in type III\n                    <jats:italic>TgROP18<\/jats:italic>\n                    , which is necessary for TgROP18 expression. This result indicates that the\n                    <jats:italic>ROP18<\/jats:italic>\n                    promoter was active in the most recent common ancestor of these two species and that it was subsequently inactivated in progenitors of the type III lineage. Overall, these data suggest that the virulence differences between these species are not solely due to the functionality of these key virulence factors. This study provides evidence that other mechanisms, such as differences in gene expression or the lack of currently uncharacterized virulence factors, may underlie the phenotypic differences between these species.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1304322110","type":"journal-article","created":{"date-parts":[[2013,4,15]],"date-time":"2013-04-15T21:53:08Z","timestamp":1366062788000},"page":"7446-7451","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["<i>Hammondia hammondi<\/i>\n                    , an avirulent relative of\n                    <i>Toxoplasma gondii<\/i>\n                    , has functional orthologs of known\n                    <i>T. gondii<\/i>\n                    virulence genes"],"prefix":"10.1073","volume":"110","author":[{"given":"Katelyn A.","family":"Walzer","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA 15260;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaw","family":"Adomako-Ankomah","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA 15260;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Dam","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA 15260;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daland C.","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, D-16868 Wusterhausen, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gereon","family":"Schares","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, D-16868 Wusterhausen, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitender P.","family":"Dubey","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, US Department of Agriculture, Beltsville, MD 20705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon P.","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA 15260;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,4,15]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/aje\/154.4.357","article-title":"Toxoplasma gondii infection in the United States: Seroprevalence and risk factors","volume":"154","author":"Jones JL","year":"2001","unstructured":"JL Jones, et al., Toxoplasma gondii infection in the United States: Seroprevalence and risk factors. 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