Mastering Malaria: The Hawaiian ‘Amakihi uses a variety of genes to combat avian malaria

Genetic analyses reveal selection for certain gene classes, but not the same genes.

Malaria is not only a human problem, birds have to cope with it too. Avian malaria,  caused by the parasite Plasmodium, occurs globally and is spread by mosquitoes. One of these mosquito vectors Culex quinquefasciatus has been introduced on Hawaii where avian malaria has impacted the radiation of Hawaiian Honeycreepers. At least seven extinction events and the population declines of the surviving species can be attributed to avian malaria. Birds have several strategies for dealing with malaria. They can try to avoid it or adapt to it. Hawaiian honeycreepers have done both: some populations moved to higher elevations where the mosquitoes cannot survive, while other populations remained in the lowlands and developed immunity to the disease.



A few members of the Hawaiian honeycreeper radiation (from:


Adapting ‘Amakihi

A recent study in the journal Molecular Ecology focused on the ‘Amakihi (Chlorodrepanis virens) which consists of both susceptible populations at high altitude and tolerant populations in low elevation. Loren Cassin-Sackett and her colleagues wanted to pinpoint the genetic changes responsible for the tolerance of these birds. Therefore, they probed the genomes of the ‘Amakihi populations for genes under positive selection using a suite of statistical tests.


The ‘Amakihi © Bettina Arrigoni | Wikimedia Commons


MHC and others

The analyses revealed some predicted genes, such as the major histocompatibility complex (MHC). This set of genes codes for cell surface proteins essential for the immune system to recognize pathogens, such as bacteria and viruses. The MHC molecules bind to the pathogens (specifically their antigens) and present them on the cell surface for recognition by the appropriate T-cells that consequently eliminate the pathogens.

In addition, several candidate genes popped up. Most of them are other infection- and immune-related genes, such as Toll-like receptors and interferons. An interesting candidate gene that is not involved in the immune response codes for an erythrocyte membrane protein. This protein is used by Plasmodium (the pathogen causing malaria) to cause cells to aggregate so it can easily infect more red blood cells. In the ‘Amakihi, this gene might be under positive selection to prevent the formation of such aggregations.


The ‘Amakihi © Sharif Uddin | eBird


Selection on gene classes, not specific genes

I have written before that it is always dangerous to tell just-so-stories based on a collection of outlier genes. The researchers are aware of this and state that “genes inferred with these approaches should be treated not as conclusive genes involved in malaria protection, but as candidates for further studies.” However, the fact that some of these candidate genes were found in multiple analyses suggests that they might be more than just candidates.

Comparing the candidate genes between different immune populations revealed an interesting pattern. Different genes were under selection in different populations. These genes, however, did belong to the same classes, namely infection- and immune-related genes. This finding nicely illustrates that evolution is partly predictable (selection on the same gene classes) and partly contingent on population-specific variation (selection on specific genes). Selection works with the available material to help individuals overcome challenges. In this case, the ‘Amakihi birds needed to fend off malaria and it didn’t matter which genes they used to do it. As long as it works…



Cassin-Sackett, L., Callicrate, T.E. & Fleischer, R.C. (2019) Parallel evolution of gene classes, but not genes: Evidence from Hawai’ian honeycreeper populations exposed to avian malaria. Molecular Ecology, 28:568-583.

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