On 2015 Oct 26, Gustav van Niekerk commented:

It would be hard to over emphasise the intense selective pressure that pathogens place on host populations (as predicted by the Red Queen hypothesis). Our genome are littered with pseudonized genes formerly associated with immune-related functions. These ‘genomic fossils’ representing discarded immunological innovations that became redundant as our pathogens evolve strategies to defeat them, testifying to an ancient conflict that have been ranging on between host and pathogens. Sequencing genomes have repeatedly demonstrated that genes with immunological functions tend to be under selective pressure and tend to be highly polymorphic (Mother Nature is ‘diversifying’ the ‘portfolio’ of immunological strategies: a pathogens can overcome many immunological strategies, but not all of them simultaneously. This observed immunological heterogeneity in population is how a species ‘hedge it’s bet’ against pathogens). Host and pathogen/parasites occasionally demonstrate "mirror-image phylogenies", demonstrating the close coevolution as pathogens keep in step with host development. Collectively, such observations suggest that pathogens exerts immense evolutionary pressure and one of the biggest drivers for evolutionary novelty.

Consequently, we suggest a less exiting narrative in which an AIS evolved initially in response to pathogen stress. Similar to your work Corcos D, 2015, we also noted that AIS evolved in an aquatic environment. Sediment and marine environments typically have a higher pathogen burden (see references in < PMID: 25698354 >), thus suggesting a higher level of pathogen stress. However, as you point out, there are scepticism about whether the AIS represent a true immunological innovation, as invertebrates do not seem any worse-off than vertebrates in suffering from infections. In this regard, we would like to point out that the AIS could have been an initial innovation that was subsequently overcome by fast evolving pathogens. That is, the AIS could have evolved in response to pathogen stress, providing an initial benefit to vertebrates, but was subsequently overcome by pathogens. And now, regardless whether the AIS is currently an ‘immunological innovation’, we are stuck with it (for better or worse). Finally, it is not obvious that the AIS do not repeat a lasting innovation. After all, “[v]ertebrates are the dominant group of animals on the Earth, given their abundance, large body sizes and presence at the top of both aquatic and terrestrial foodwebs” Wiens JJ, 2015. How did vertebrates manage to survive (and indeed flourish) in a world initially dominated by invertebrates? An AIS may have some additional benefits that have helped vertebrates invade into niches previously occupied by invertebrates. How AIS could provide a benefit that is (a) only applicable to vertebrates and (b) does not involve an enhancement of immune potency is currently an open question.

(PS we unfortunately do not have institutional access to the article from Burnet FM. We will shortly be sending a letter to the editor, commenting on your Corcos D, 2015 interesting article)

On 2015 Oct 20, Daniel Corcos commented:

This paper is interesting for examining the relationship between the adaptive immune system and the vascular system. However it does not explain such a complexity with no obvious advantage. For instance, immunodeficiency in zebrafish does not result in a dramatic change in viability. This can be interpreted in the words of Hedrick as an indication that the AIS is "not so superior"(1) or in the words of Burnet that it is "related to something other than defence against pathogenic microorganisms."(2) I have proposed (3) that its origin was related to intraspecific predation (cannibalism).

1)Hedrick SM. Immune system: not so superior. Science 2009;325:1623–4.

2)Burnet FM. “Self-recognition” in colonial marine forms and flowering plants in relation to the evolution of immunity. Nature 971;232:230–5.

3)Corcos D. Food-Nonfood Discrimination in Ancestral Vertebrates: Gamete Cannibalism and the Origin of the Adaptive Immune System. Scand J Immunol. 2015;82(5):409-17.

On 2015 Oct 20, Daniel Corcos commented:

This paper is interesting for examining the relationship between the adaptive immune system and the vascular system. However it does not explain such a complexity with no obvious advantage. For instance, immunodeficiency in zebrafish does not result in a dramatic change in viability. This can be interpreted in the words of Hedrick as an indication that the AIS is "not so superior"(1) or in the words of Burnet that it is "related to something other than defence against pathogenic microorganisms."(2) I have proposed (3) that its origin was related to intraspecific predation (cannibalism).

1)Hedrick SM. Immune system: not so superior. Science 2009;325:1623–4.

2)Burnet FM. “Self-recognition” in colonial marine forms and flowering plants in relation to the evolution of immunity. Nature 971;232:230–5.

3)Corcos D. Food-Nonfood Discrimination in Ancestral Vertebrates: Gamete Cannibalism and the Origin of the Adaptive Immune System. Scand J Immunol. 2015;82(5):409-17.

On 2015 Oct 26, Gustav van Niekerk commented:

It would be hard to over emphasise the intense selective pressure that pathogens place on host populations (as predicted by the Red Queen hypothesis). Our genome are littered with pseudonized genes formerly associated with immune-related functions. These ‘genomic fossils’ representing discarded immunological innovations that became redundant as our pathogens evolve strategies to defeat them, testifying to an ancient conflict that have been ranging on between host and pathogens. Sequencing genomes have repeatedly demonstrated that genes with immunological functions tend to be under selective pressure and tend to be highly polymorphic (Mother Nature is ‘diversifying’ the ‘portfolio’ of immunological strategies: a pathogens can overcome many immunological strategies, but not all of them simultaneously. This observed immunological heterogeneity in population is how a species ‘hedge it’s bet’ against pathogens). Host and pathogen/parasites occasionally demonstrate "mirror-image phylogenies", demonstrating the close coevolution as pathogens keep in step with host development. Collectively, such observations suggest that pathogens exerts immense evolutionary pressure and one of the biggest drivers for evolutionary novelty.

Consequently, we suggest a less exiting narrative in which an AIS evolved initially in response to pathogen stress. Similar to your work Corcos D, 2015, we also noted that AIS evolved in an aquatic environment. Sediment and marine environments typically have a higher pathogen burden (see references in < PMID: 25698354 >), thus suggesting a higher level of pathogen stress. However, as you point out, there are scepticism about whether the AIS represent a true immunological innovation, as invertebrates do not seem any worse-off than vertebrates in suffering from infections. In this regard, we would like to point out that the AIS could have been an initial innovation that was subsequently overcome by fast evolving pathogens. That is, the AIS could have evolved in response to pathogen stress, providing an initial benefit to vertebrates, but was subsequently overcome by pathogens. And now, regardless whether the AIS is currently an ‘immunological innovation’, we are stuck with it (for better or worse). Finally, it is not obvious that the AIS do not repeat a lasting innovation. After all, “[v]ertebrates are the dominant group of animals on the Earth, given their abundance, large body sizes and presence at the top of both aquatic and terrestrial foodwebs” Wiens JJ, 2015. How did vertebrates manage to survive (and indeed flourish) in a world initially dominated by invertebrates? An AIS may have some additional benefits that have helped vertebrates invade into niches previously occupied by invertebrates. How AIS could provide a benefit that is (a) only applicable to vertebrates and (b) does not involve an enhancement of immune potency is currently an open question.

(PS we unfortunately do not have institutional access to the article from Burnet FM. We will shortly be sending a letter to the editor, commenting on your Corcos D, 2015 interesting article)