# Mechanistic analysis of a pathway that integrates allorecognition and altruism in Dictyostelium

> **NIH NIH R35** · BAYLOR COLLEGE OF MEDICINE · 2024 · $549,652

## Abstract

Allorecognition is the ability to discriminate self from non-self or kin from non-kin. It is observed in various
processes in every life kingdom, including immunity, development, sexual reproduction, and sociality.
Cooperation is another ubiquitous property that involves interactions between individuals, ranging from
interactions between single cells to interactions between groups of multicellular organisms. The evolution of
cooperation is a challenging riddle and one of its most perplexing aspects is altruism – the act of benefiting
another individual at an expense to the actor. Altruism is essential for cooperation but its evolutionary
advantages cannot be understood without considering allorecognition. The greenbeard hypothesis bridges the
concepts of allorecognition and altruism. Dawkins’ book ‘The Selfish Gene’ popularized Hamilton’s concept of
a genetic locus that exhibits three key properties – displaying a discernable signal, recognizing that signal in
others, and acting altruistically toward other individuals that display the signal. This idea was first considered
as a hypothetical situation that was unlikely in nature, but studies over the past three decades have
documented it in various organisms, including pathogenic bacteria, social insects, and even humans.
Nevertheless, most of these studies did not fully account for the third criterion, namely a direct relationship
between the greenbeard pathway and altruism. The allorecognition system of Dictyostelium discoideum relies
on two polymorphic compatible membrane proteins, TgrB1 and TgrC1. It has been described as a greenbeard
system in which TgrC1 confers the ability to signal kinship and TgrB1 confers the ability to recognize the
signal, but the altruistic act of stalk formation has not been directly attributed to these proteins. We hypothesize
that the tgrB1-tgrC1 pathway is a greenbeard system that confers the three elements of signaling, recognition,
and altruism, and that mutations in the pathway genes confer falsebeard cheating behaviors. We have recently
discovered that mutational activation of TgrB1 confers altruism in that cells that express the mutant protein
enhance the sporulation efficiency of their wild-type counterpart at an expense to themselves. We also
discovered that mutating downstream elements of the pathway confers falsebeard behaviors – inactivation of
the rapgapB or rasD genes and activation of rapA cause cheating among cells that display matching TgrB1
and TgrC1 signals. These mutations are directly related to the tgrB1-tgrC1 system because knocking out
rapgapB suppresses the developmental defects conferred by inactivation of the tgrB1-tgrC1 system, and rasD
and rapA are tightly related to rapgapB signaling. These pioneering findings directly link allorecognition and
altruism in one greenbeard pathway. We will study how activating mutations in tgrB1 confer altruistic behavior,
and how mutations that modify rapgapB, rapA, and rasD cause falsebeard cheating. Usi...

## Key facts

- **NIH application ID:** 10755780
- **Project number:** 1R35GM152113-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** GAD SHAULSKY
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $549,652
- **Award type:** 1
- **Project period:** 2024-07-10 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10755780

## Citation

> US National Institutes of Health, RePORTER application 10755780, Mechanistic analysis of a pathway that integrates allorecognition and altruism in Dictyostelium (1R35GM152113-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10755780. Licensed CC0.

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