Keeping with the geneticts theme, 50,000-year-old gene reveals how deadliest malaria parasite jumped from gorillas to humans

Molly Campbell of Technology Networks writes in a study published last week  in PLOS Biolgy, researchers from the Wellcome Sanger Institute and the University of Montpellier have reconstructed a ~50,000-year-old gene sequence acquired by the ancestor of Plasmodium falciparum. The acquisition of the gene sequence enabled the parasite to infect human red blood cells.
The gene, known as Rh5, enabled the parasite to infect both gorillas and humans for a limited period of time. The study provides insight in the molecular mechanisms behind this jump.

Malaria causes 435,000 deaths per year on average, with ~61% occurring in children <5 years of age. P. falciparum is the of seven species of parasite that can cause malaria in a family known as the Laverania and causes the deadliest form of the infectious disease; in 2017, this parasite accounted for 99.7% of cases in Africa.

The Laverania parasites originated in African great apes; however, they are now restricted to their own specific host species. Three parasite species are confined to chimpanzees, and three are combined to gorillas. What about the seventh, you ask?

Pfalciparum only infects humans now, as it switched host from gorillas. This process whereby a disease is transmitted to humans from an animal is known as zoonosis. But how exactly did the switching of the parasite from gorillas to humans occur at the molecular level?

Gavin Wright, lead author of the study and Senior Group Leader at the Wellcome Sanger Institute, said: “In the history of mankind, Plasmodium falciparum malaria has arguably been responsible for more human deaths than any other disease. So, it is both important and fascinating to understand the molecular pathways that enabled this deadly parasite to infect humans.”
The evolution of P. falciparum and malaria

The scientists conducted genome sequencing of all seven Laverania parasite species, and uncovered a section of DNA that had been transferred from a gorilla parasite, Plasmodium adleri,  to the ancestor of P. falciparum. The gene sequence included Rh5, a gene that produces the protein reticulocyte binding-like protein 5, which binds to a protein receptor in human red blood cells known as basigin. The interaction of this protein and its receptor is critical for the P. falciparum parasite to infect humans, and thus Rh5 is showing promise as a potential malaria vaccine target. If scientists can disrupt the interaction, the parasite cannot enter the red blood cell and cause disease.

The research team at the University of Montpellier wanted to understand further the ancestral origins of P. falciparum. They therefore adopted ancestral sequence reconstruction to effectively “reconstruct” the Rh5 DNA sequence that had been transferred to the ancestor of P. falciparum all those 50,000 years ago. The scientists at the Wellcome Sanger Institute then created synthetic copies of the Rh5 gene in the laboratory, enabling the molecular interactions of the encoded Rh5 protein to be explored.
Interestingly, the study findings demonstrate that the transferred Rh5 protein possessed dual binding ability for the red blood cell receptor in both humans and gorillas – thus demonstrating how P. falciparum was able to switch hosts.

Francis Galaway, first author of the study and Staff Scientist at the Wellcome Sanger Institute, said: “The fact that this ancestral RH5 protein was able to bind to the red blood cell receptor basigin from both humans and gorillas, immediately provided a molecular explanation for how P. falciparum evolved to infect humans.”

But how did P. falciparum become restricted to humans? The researchers identified six differences between the ancestral Rh5 gene sequence, and the current sequence observed in P. falciparum. Surprisingly, one specific mutation resulted in the complete loss of ability to bind the gorilla form of basigin, depicting how the parasite became restricted to humans.

Franck Prugnolle, from the University of Montpellier, said: “It’s fascinating to be able to ‘resurrect’ ancestral genes such as the one which allowed Plasmodium falciparum to jump from gorillas to humans. We’ve discovered not only how a species host switch has occurred, but the individual mutation which has then restricted P. falciparum to a single host species.”

The scientists hypothesize that the genetic transfer of the Rh5 gene occurred when a gorilla cell was infected with two species of the Plasmodium parasite in parallel – known as introgression.

This form of introgression is extremely rare. Of the seven Laverania species, genomic analyses have revealed only a few instances of this occurring over a span of approximately one million years.

I loves me my fruit: It may explain my big brain (sic)

Passion fruit and mangoes are enough reason to move to Australia.

Sure, there are American versions, but not like these.

Bret Stetka of Scientific American writes that compared with other mammals, and along with those of a few other notably bright creatures—dolphins, whales and elephants among them—the brain to body-size ratios of monkeys, apes and humans are among the highest.

For decades the prevailing evolutionary explanation for this was increasing social complexity. The so-called “social brain hypothesis” holds that the pressures and nuances of interacting and functioning within a group gradually boosted brain size.

Yet new research suggests otherwise. A study conducted by a team of New York University anthropologists, and published Monday in Nature Ecology & Evolution, reports diet was in all likelihood much more instrumental in driving primate brain evolution. In particular, it appears that we and our primate cousins may owe our big brains to eating fruit.

I love my fruit.

In Guelph, I was the hockey coach who always ate a grapefruit during the game. I still do when I coach in Australia, but more towards the sweeter fruits.

That must be why I’m so smart (not).

Much of the research exploring the social hypothesis has rendered inconsistent results. And as many in the field have noted, a number of oft-cited studies in support of the theory suffer from small sample sizes and flawed design, including out-of-date species classification. The new work is based on a primate sample more than three times larger than that used in prior studies, and one that used a more accurate evolutionary family tree.

In over 140 primate species, the study authors compared brain size with the consumption of fruit, leaves and meat. They also compared it with group size, social organization and mating systems. By looking at factors such as whether or not a particular primate group prefers solitary to pair living or whether they are monogamous, the researchers figured they should theoretically be able to determine if social factors contributed to the evolution of larger brains.

And it appears they could not. Dietary preferences—especially fruit consumption—seems to have been much more influential. The researchers found that fruit-eating species, or frugivores, have significantly larger brains than both omnivores and “foliovores,” those that prefer eating leaves. “These findings call into question the current emphasis on the social brain hypothesis, which suggests larger brains are associated with increased social complexity,” explains Alex DeCasien, a doctoral candidate in anthropology and lead author of the study. “Instead, our results resurrect older ideas about the evolutionary relationship between foraging complexity and brain size.”


The evolution of dangerous E. coli

Enterohemorrhagic Escherichia coli (EHEC) is the causative agent of bloody diarrhea and extraintestinal sequelae in humans, most importantly hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP).

dangerBesides the bacteriophage-encoded Shiga toxin gene (stx), EHEC harbors the locus of enterocyte effacement (LEE), which confers the ability to cause attaching and effacing lesions. Currently, the vast majority of EHEC infections are caused by strains belonging to five O serogroups (the “big five”), which, in addition to O157, the most important, comprise O26, O103, O111, and O145.

We hypothesize that these four non-O157 EHEC serotypes differ in their phylogenies. To test this hypothesis, we used multilocus sequence typing (MLST) to analyze a large collection of 250 isolates of these four O serogroups, which were isolated from diseased as well as healthy humans and cattle between 1952 and 2009. The majority of the EHEC isolates of O serogroups O26 and O111 clustered into one sequence type complex, STC29. Isolates of O103 clustered mainly in STC20, and most isolates of O145 were found within STC32. In addition to these EHEC strains, STC29 also included stx-negative E. coli strains, termed atypical enteropathogenic E. coli (aEPEC), yet another intestinal pathogenic E. coli group. The finding that aEPEC and EHEC isolates of non-O157 O serogroups share the same phylogeny suggests an ongoing microevolutionary scenario in which the phage-encoded Shiga toxin gene stx is transferred between aEPEC and EHEC.

As a consequence, aEPEC strains of STC29 can be regarded as post- or pre-EHEC isolates. Therefore, STC29 incorporates phylogenetic information useful for unraveling the evolution of EHEC.

Highly virulent non-O157 enterohemorrhagic Escherichia coli (ehec) serotypes reflect similar phylogenetic lineages, providing new insights into the evolution of EHEC

Applied and Environmental Microbiology, October 2015, Volume 81, Number 20

Inga Eichhorn, Katrin Heidemanns, Torsten Semmler, Bianca Kinnemann, Alexander Mellmann, Dag Harmsen, Muna F. Anjum, Herbert Schmidtf Angelika Fruth, Peter Valentin-Weigand, Jürgen Heesemann, Sebastian Suerbaum, Helge Karchc, and Lothar H. Wieler