Joined: May 2002
Interesting article comparing animal and plant immune systems:
Same Tools, Different BoxesConvergent evolution plays out in plant and animal innate immunity | By Philip Hunter
As life's diversity demonstrates, nature has a pretty large toolbox for designing adaptations. While in many ways an efficient builder, it often reuses blueprints, even if not starting with the same tools. Analogous wing structures in bird and bat suggest a why-mess-with-success ethos. New World cacti and desert-dwelling Euphorbiaceae in the Old World share protective spines and photosynthesizing stems even though the last common ancestor predates such modifications.
Beyond structural adaptations, researchers are investigating convergent evolution at the molecular level, and this may allow for broader comparisons even between plants and animals. Both, of course, share the building blocks and fundamental biochemistry that evolved before the two kingdoms presumably diverged from common single-celled ancestors. But with their radically different cell structures, plants and animals were thought to have pursued largely independent evolutionary routes. Such disparity was reflected in the lack of interaction between the respective research communities.
But much is changing, especially with respect to the study of innate immunity, which turns out to involve strikingly similar mechanisms in both plants and animals. One can find resemblances in the receptors that recognize pathogenic components such as lipopolysaccharide; in the signaling systems that initiate responses through kinase cascades; and in the defense mechanisms, including reactive molecules such as nitric oxide, says Jonathan Jones, senior scientist at the Sainsbury Laboratory of the John Innes Centre in Norwich, UK.
Moreover, says Jones, autoimmune disorders can develop in plants as well as animals. In many cases, researchers consider plant and animal innate-immunity analogs to have evolved independently, because the underlying genes involved are radically different. Here, convergence is occurring purely at the functional level, according to Daniel Klessig, president and CEO of Boyce Thompson Institute (BTI) for Plant Research in Ithaca, NY. But now, say some, both functional and genetic similarities between plant and animal immunity are leading to cross-pollination between the respective research fields.
NOS BY ANY OTHER NAME Functional similarities can exist without accompanying sequence homologies. Klessig offers parallels in nitric oxide production between plants and animals. Nitric oxide is believed to exert direct anti-microbial effects by interfering with protein function and forming cytotoxic oxidants.
Klessig's group recently discovered the enzyme responsible for nitric oxide production in plants, a variant of the glycine decarboxylase complex's P protein.1 This plant nitric oxide synthase (NOS) shares biochemical and kinetic features with animal NOSs, says Klessig.
"Like the mammalian NOS, it is induced or activated by infection and has very high specific activity. We have also recently, in collaboration with Greg Martin's group [also at BTI] shown that like in animals, silencing of the plant NOS suppresses disease resistance." Although the animal and plant NOSs are very similar in what they do, not much of the underlying genetic sequence is common. "This suggests they use different chemistry for nitric oxide production," says Klessig.
There are some proteins common to plants and animals with considerable sequence homology, but researchers dispute whether many of these evolved purely to serve innate immunity. Some hypothesize that the evolution of mitogen-activated protein kinases (MAPKs) was driven at least partly by the requirements of innate immunity. MAPKs largely regulate mitosis, but they also have been implicated in the innate immune response as a signaling intermediary connecting recognition and response mechanisms, with some apparently striking parallels in plants and animals. Interference with MAPK signaling depletes resistance in both plants and animals. But while there is evidence that MAPK signaling has a role in programmed cell death to stop the spread of bacterial or viral infection, the exact nature of the immune responses elicited by the signaling is unknown.2
According to plant immunologist Jeff Dangl at the department of biology, University of North Carolina, Chapel Hill, some sequence homology in the MAPKs would be expected, given that genes encoding for kinase cascades account for about 10% of most eukaryote genomes. MAPKs have been widely available throughout evolution for a variety of signaling functions. "If you're going to do something, you'll pull something out of the toolkit," says Dangl. Here parallel paths to innate immunity modified a common tool developed for other functions.
Yet, some aspects of innate immunity require convergence at the molecular level, notably in common pathogen receptors. This can involve direct recognition of factors on the pathogen's surface, or response to pathogen proteins injected into the cell. Pathogens produce proteins that interfere with the host defenses, says Jones. In turn, the host has evolved proteins in an effort to negate the effect of pathogen interference, leading to a long-term molecular arms race. "You've got these layers of yin and yang between the host and the parasite," Jones notes.
Some responses are conserved between plants and animals. To grow in any host, flora or fauna, bacteria must identify their environment and then switch on genes to encode the proteins required for replication under those conditions. A primary locus for Gram-negative bacteria is the HRP gene locus, which encodes the Type III machinery that secretes so-called effector proteins directly into the cell. Mary Beth Mudgett,2 assistant professor of biology at Stanford University, focuses on the molecular mechanisms used collectively by Type III effector proteins to suppress host defenses. Mudgett's work is in plants, but a class of Type III effector protein is conserved between the bacteria infecting both plants and animals. The animal-infecting bacteria produce YopJ, but plant-pathogen versions now have been discovered sharing a key, four-amino-acid catalytic site. YopJ and its counterpart operate by cutting a protein involved in the MAPK cascade, blocking the pathway as a result.3
HOMOLOGY IN THE CARDS Significant similarities exist between some plant and animal receptors involved in sensing pathogen surface proteins, Jones says. He cites the case of NB/LRR proteins in plants, which have similar functions and sequences to the CARD4 and CARD15 proteins in animals. These proteins recognize lipopolysaccharides found on the outer membranes of some bacteria, and transduce internal cellular responses.4 The molecular characterization of these proteins has revealed that in plants and animals, similar domains are used in pathogen recognition and response initiation. This has stimulated debate over whether these proteins evolved specifically for disease resistance or whether it is another case of innate immunity reaching into the common toolkit.
Whatever the case, the overlap between CARD15 and NB/LRR has had felicitous implications for research into Crohn disease. A mutation in CARD15 increases susceptibility to Crohn, possibly by creating an inflammatory response to benign gut bacteria antigens.4 And the similarity with NB/LRR makes it possible to study gene mutants in plants. Dangl says that the genetics of resistance is easier to study in plants than in animals such as mice. "The plant guys are well ahead of the animal guys in terms of knowing what genes in the host are needed to transduce a signal perceived by these receptors, because it is easier to do experiments to isolate mutants," says Dangl. In other words, the genes involved in signaling the innate response to gut bacteria in humans can be studied to some extent in rapidly growing plants such as Arabidopsis. For this reason, plant work has now been well cited by Crohn disease researchers, according to Dangl. >P> And though there's nothing analogous to Crohn disease, plants can experience autoimmune disorders, such as the so-called paranoid plant syndrome. Paranoid plants include a collection of disease lesion-mimic mutants (Les) in maize that spontaneously form necrotic lesions usually seen in diseased plants. Also, Arabidopsis mutants for MAPK 4 are stunted and display systemic defenses, such as salicylic-acid production, even in the absence of a pathogen.5 Here, the mutation of a negative immune regulator confers resistance to a number of infections.
"Defense pathways that are powerful need strong negative regulation, and autoimmune diseases can occur when this negative regulation does not work," says Jones. The existence of autoimmune disease in plants is interesting, but has no significance for human conditions such as arthritis, he says.
But the overlap between plant and animal immunity may have potential significance for piecing together the innate system's finer pathways. Dangl concedes that the plant research community, of which he is a part, has been quick to exploit these connections to compete for funding generally destined for animal studies. "The animal guys ignored us," he says. Now they must take notice.
Philip Hunter (firstname.lastname@example.org) is a freelance writer in London.
1. M.R. Chandok et al., "The pathogen-inducible nitric oxide synthase (iNOS) in plants is a variant of the P protein of the glycine decarboxylase complex," Cell, 113:469-82, 2003.
2. R.A. Alegado et al., "Characterization of mediators of microbial virulence and innate immunity using the Caenorhabditis elegans host-pathogen model," Cell Microbiol, 5:435-44, 2003.
3. A. Hotson et al., "Xanthomonas type III effector XopD targets SUMO-conjugated proteins in plants," Mol Microbiol, 50:377-89, 2003.
4. J.P. Roberts, "An immunological role in the CARDs," The Scientist, 17:29-30, Oct. 20, 2003.
5. M. Petersen et al., "Arabidopsis MAP kinase 4 negatively regulates systemic acquired resistance," Cell, 103:1111-20, 2000.