Marine mammals and the legacy of gene loss: evolutionary biology informs policy

https://upload.wikimedia.org/wikipedia/commons/0/0f/4_Walross_2001.jpg
Walruses, whales, and all other marine mammals are at risk from agricultural run-off due to ancient gene loss. Photo credit: Ansgar Walk, Wikimedia Commons.

Life began in the water.  Microbes swarmed around in primordial ooze, banded together to form multicellular organisms, and eventually grew complex enough to leave their watery homes and become the terrestrial animals that exist today.  Some of those land-dwelling creatures became mammals, and in a surprising twist, three separate lineages of ancient mammals then returned to the ocean to give rise to modern-day whales and dolphins, manatees and dugongs, and seals and walruses.  These species developed characteristics to help them thrive in an aquatic environment, including smooth skin, webbed flippers, and increased diving capability. But did they undergo the same genetic changes to develop these characteristics? My lab sought to answer this question, and in the process discovered a conservation crisis millions of years in the making (1).  It all started by tracing the lineage of defunct genes.

My labmate Dr. Wynn Meyer was specifically interested in gene loss, or, more precisely, loss of function, in marine mammals.  These genes still retain traces of their original sequence, but they can no longer be translated into functional proteins. Gene loss is a drastic change in an organism – once a gene is gone, it’s gone for good – so we would only expect to see lots of gene loss when species undergo extreme changes, such as transitioning from a terrestrial to a marine environment.  My lab developed a method to find non-functional genes based on their genetic sequence in 58 mammal species. We then searched for genes that are functional in terrestrial mammals and non-functional in marine mammals – these genes may have been lost because mammals returned to the ocean. We discovered 23 such genes, half of which had functions related to sense of taste and smell that are unimportant to marine mammals because those senses are unnecessary in aquatic environments.  Since marine mammals hold their breath when underwater, they cannot smell things in the water the same way terrestrial mammals can smell things on land. Likewise, a sense of taste that is useful on land is less useful for tasting things in the water. However, the highest-scoring result from our analyses, and the star of the show, was a gene called PON1 that doesn’t have any apparent association to smelling or tasting.

PON1, short for paraoxonase 1, encodes a protein associated with metabolism of fats that may serve to prevent plaque build-up in mammalian blood vessels.  We still aren’t sure exactly why PON1 was originally lost in marine species.  “I was very curious because there wasn’t a clear story about it,” says lead investigator Dr. Meyer.  “We had found things…that we expected because of their association with the marine trait, but PON1 didn’t check any of those boxes.”  Dr. Meyer investigated numerous possible reason for PON1’s loss, but she whittled her ideas down to two current working hypotheses.  She believes PON1’s loss was related to either marine mammals’ transition to an aquatic diet or the necessity for long, deep diving in the marine environment.  Whatever the precise reason, PON1’s primary loss occurred because it was unimportant to the survival of marine mammals.  However, in the modern world, PON1 has a new function that makes its loss detrimental to those species.  In most mammals today, PON1 breaks down toxic organophosphates found in pesticide by-products, which are often found in marine environments due to agricultural runoff.  

Our sequence-based analysis indicated that PON1 shows a striking pattern of loss in marine mammals the gene appears to be functional in all terrestrial mammals tested and non-functional in all the marine mammals that would leave marine species unprotected from the toxic effects of pesticides in their environments.  This idea is particularly alarming in light of the fact that pesticides have been found in coastal waters surrounding Florida and Australia that house at-risk species like manatees and dugongs.  To further measure marine species’ abilities to combat toxic chemicals, our collaborators tested blood samples from both marine and terrestrial mammals to measure their ability to break down pesticide by-products.  Marine mammal blood showed minimal activity compared to terrestrial mammal blood, which further supports the claim that marine mammals have little natural defense against organophosphate pesticides.

https://upload.wikimedia.org/wikipedia/commons/7/71/The_head_of_Dugong_dugon.jpg
Coastal-dwelling dugongs and manatees are likely to be especially vulnerable to organophosphate pesticides, due to their non-functional PON1 gene. Photo Credit: Camille Menard, Wikimedia Commons.

Our work adds another voice to an ongoing debate over banning one widely-used organophosphate-based pesticide called chlorpyrifos not only because of the danger it poses to marine mammals, but also because of the damage it can cause in humans.  The E.P.A. has been hesitant to ban chlorpyrifos because of the extraordinary impact it would have on the farm industry chlorpyrifos is one of the most prevalent pesticides in the United States, with over 5 million pounds sold yearly (2).  However, numerous scientific studies, some of which were reported as early as the 2000s, have discovered negative consequences of chlorpyrifos exposure during childhood (313).  Most notably, it hinders brain development, which results in lower IQ and decreased brain size in affected children.  Despite the chemical’s popularity, in 2001, the E.P.A. banned chlorpyrifos use in homes, and in 2015 it recommended also banning the chemical for agricultural use (14).  Strangely, the E.P.A. reversed course in 2017 and began supporting continued use of chlorpyrifos as an agricultural pesticide, but in 2018 a court ordered the E.P.A. to ban chlorpyrifos because of the mounting scientific evidence indicating its hazardousness (15).  Our findings complement the existing data that support the toxicity of chlorpyrifos and add a new angle – a chemical that is dangerous to humans may be even more so for our marine brethren because of their unique evolutionary history.  What began as basic science research to explore mammals’ adaptations to a new environment quickly grew into a story with colossal significance to not only marine conservation efforts, but also the heated discussion at the interface where science meets policy.

 

  1.     W. K. Meyer et al., Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals. Science. 361, 591–594 (2018).
  2. Appeals Court Orders EPA to Ban a Pesticide Known to Harm Children. Time (2018), (available at http://time.com/5363553/epa-chlorpyrifos-ban-pesticide/).
  3.     V. Rauh et al., Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ. Health Perspect. 119, 1196–201 (2011).
  4.     V. A. Rauh et al., Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics. 118, e1845-59 (2006).
  5.     V. A. Rauh et al., Brain anomalies in children exposed prenatally to a common organophosphate pesticide, doi:10.1073/pnas.1203396109.
  6.     S. M. Engel et al., Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ. Health Perspect. 119, 1182–8 (2011).
  7.     B. Eskenazi et al., Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environ. Health Perspect. 115, 792–8 (2007).
  8.     R. M. Whyatt et al., Prenatal insecticide exposures and birth weight and length among an urban minority cohort. Environ. Health Perspect. 112, 1125–32 (2004).
  9.     M. F. Bouchard et al., Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ. Health Perspect. 119, 1189–95 (2011).
  10.     A. R. Marks et al., Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study. Environ. Health Perspect. 118, 1768–74 (2010).
  11.   S. M. Engel et al., Prenatal Organophosphate Metabolite and Organochlorine Levels and Performance on the Brazelton Neonatal Behavioral Assessment Scale in a Multiethnic Pregnancy Cohort. Am. J. Epidemiol. 165, 1397–1404 (2007).
  12.   J. G. Young et al., Association Between In Utero Organophosphate Pesticide Exposure and Abnormal Reflexes in Neonates. Neurotoxicology. 26, 199–209 (2005).
  13.   G. Berkowitz et al., In Utero Pesticide Exposure, Maternal Paraoxonase Activity, and Head Circumference. Environ. Health Perspect. 112, 388–391 (2004).
  14.   E. Willingham, What We Know About Chlorpyrifos, The Pesticide the EPA Thinks Is Ban But Won’t Ban. Forbes (2017).
  15.   E. Lipton, Court Orders E.P.A. to Ban Chlorpyrifos, Pesticide Tied to Children’s Health Problems. New York Times (2018).
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