Cetacean Evolution: Gene Loss, Was It On Porpoise?

Adaptive gene loss in Cetaceans as a mechanism for rapid evolution

Elise R. Baugh :

Ms. Blue A Blue whale skeleton outside The Seymour Center for marine discovery

Introduction 

Marine mammals have shown an amazing ability to adapt to their environment.

 One of the most remarkable examples of environmental adaptation is demonstrated in the evolutionary progression from Artiodactyls, hoofed terrestrial mammals, to Cetacea, fully aquatic marine mammals.  During this period, mammals transitioned from life on land to living underwater. Over the past decade, new evidence has provided the foundation for the cetacean land-to-aquatic transition in the form of transitional fossil discoveries. Egypt, India, and Pakistan have been the source for an array of intermediate fossil discoveries (Spaulding, O’Leary, Gatesy, 2009). These discoveries provide a clear evolutionary narrative of the land to sea shift supported with fossil evidence that documents multiple stages (Spaulding, et al., 2009). 

  Fossil and molecular data sets, when combined, provide evidence of cetaceans  ‘phenotypic plasticity through the mechanism of gene loss. The term ‘phenotypic plasticity’ describes an individual organism's ability to alter gene expression based on environmental factors. This is done through the loss or inactivation of ancestral protein-coding genes. Gene loss can occur via gene mutations or relaxed selection. Genetic mutations attributed to evolutionary adaptations include insertions and deletions that cause frameshift mutations, stop coding mutations, and mutations at splice sites.  These mutations ultimately inactivate protein-coding genes resulting in desirable characteristics suited to the organism's environment.(Sharma et al., 2018)

Extensive behavioral, physiological, and morphological changes had to occur during the shifting from living on land to living underwater. Here we review genetic research that explores gene loss as a mechanism for adaptation, in the cetacean’s land to water evolution.  We zero  in on  three specific physiological traits in cetaceans: unihemispheric sleep, skin adaptations, and deep-sea diving capabilities, aiming to understand how gene loss or gene inactivation plays a pivotal role in driving these physiological changes at the cellular and molecular levels.

Using comparative genomics as a tool to understand the role of gene loss in phenotypic plasticity;

Recent studies have indicated that gene loss plays an important role in mammal phenotypic plasticity (Sharma et al., 2018).  In this study, the researchers hypothesize that the genomic loss that occurred in the terrestrial-to-aquatic shift is associated with phenotypic adaptations.  To understand the genetic origins of cetacean phenotypes, they take a genomic approach to understanding the role that gene loss plays, revealing the cellular and molecular mechanisms behind cetaceans’ phenotypic plasticity.  Methodologies utilized include gene sequencing and comparative genomics on over 62 mammals.  Gene sequencing is then segregated into trait groups and analyzed for gene loss events. A hypothesis is developed regarding which gene loss events are linked to a particular phenotypic characteristic. The researchers date the incidents of loss and compare them to known ancestral splits in the ancestral cetacean lineage. This ancestral split data is essentially a timeline based on the species phylogenetic tree (Sharma et al., 2018).

If a gene loss event coincides with a split in the ancestral line, then the genome loss indicates a relative phenotypic adaptation. Finally, a comparison between species is made, comparing animals with the gene loss to those without the gene loss. The results provide evidence supporting that hypothesis (Sharma et al., 2018). The following three incidents of gene loss were discovered using the above comparative genomic methodologies (Figure 1, Figure 2, Figure 3).

Cetacean gene loss associated with skin and hair function:

Underwater mammals have different skin requirements than their land-based ancestors. They have thicker skin and other epidermal barrier needs, and they no longer need sweat glands or hair follicles (Espregueira Themudo et al., 2020, p. 1). We know from observing extant dolphin species that their skin peels and sloughs faster than humans by 8.5 times. This physical characteristic not only gives them a smooth surface but may also aid in preventing microbe colonization. (Hecker, Sharma, & Hiller, p3179-3188) So when searching for gene loss events, it is not surprising that researchers discovered that several cetacean species shared similar gene loss events associated with skin function (Table 1) . They lack the genes that express sebum and hair follicles (Figure 1), and cell adhesion (Figure 2). When the gene loss incidents occur, the timeline predictions are simultaneous or predate an ancestral split in cetaceans. Genes inactivations can be tracked to inactivation mutations and are the indicators for the major changes in cetacean skin and the skin barrier function that we see today (Sharma et al., 2018).

Cetacean gene loss and uni-hemispheric sleep:

Cetaceans have different sleep needs due to their need for oxygen in an underwater world. They have adapted the ability to allow only one-half of their brains to sleep at a time while the other halfremains awake (Mascetti, 2016, pp 221-226). In marine mammals, this is an important feature that ensures regular breathing at the surface. Also, They do not follow circadian rhythms but instead sleep when prey is not available.   Melatonin production is tied to functions that promote circadian rhythms and drop the core body temperature. (Mascetti, 2016, p 221-226). So, it is not surprising that the researchers discovered mutations that inactivate melatonin synthesis across multiple marine mammal sequences. The loss of melatonin may have been a precursor to the adoption of unihemispheric sleep (Sharma et al., 2018).  \

Genetic loss and deep-sea diving:

The forming of clots is more dangerous than helpful, if you are a deep-sea diver.  This is because while at great depths, heart rates are reduced, and blood flow slows down.  Additionally, there is an increase of pressure at great depths, causing veins and arteries to become narrower.  Therefore, if clots were to occur at these depths, they could cut off blood flow entirely (Huelsmann, Hecker, Springer, Gatesy, Sharma, Hiller, 2019, p 2). Comparative genomics has revealed that cetaceans are lacking the genes that express thrombosis.

In Conclusion

It has been said that cetaceans are the ‘poster child’ of macroevolution due to the amount of both fossils and molecular evidence available. (McGowen et al., 2014, para 1). Recent molecular research on gene loss and its role in phenotypic plasticity adds fascinating expansion to our understanding cetacean evolution. It provides another line of evidence that when combined with fossil evidence gives us clearer pictures of the molecular mechanism driving change we see in the fossil evidence .  The methodologies described in this paper have been made possible with technological improvements in comparative genomics. New technologies paired with their applicable methodologies have inspired a flurry of research and encouraged new insights into the underlying mechanisms necessary within cetacean’s evolutionary path.

The hypothesis that gene loss was the mechanism for rapid adaptation to environmental changes is a surprising concept. At first glance, one would predict that the loss of genes would translate to a loss of function. But this review of recent research demonstrates how gene loss is used to change phenotypic morphology in relatively short periods. an effective method to a changing environment. Evolutionarily, gene loss is a fascinatingly innovative way to 'make do with what you have inherited, shelving aspects of this inheritance that is undesirable in the new environment.  The inactivating mutations that result in gene loss do not completely remove the gene but merely disables them so that future shifts in the environment can be accommodated. The mechanism basically shelves the gene that is inefficient to maintain when the gene expression benefits are no longer useful.  

Literature Cited: 

Sharma, V., Hecker, N., Roscito, J. G., Foerster, L., Langer, B. E., & Hiller, M. (2018). A genomics approach reveals insights into the importance of gene losses for mammalian adaptations. Nature communications, 9(1), 1215. DOI: https://doi.org/10.1038/s41467-018-03667-1

Huelsmann M, Hecker N, Springer MS, Gatesy J, Sharma V, Hiller M.(2019) Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations. Science Advances. 2019 Sep 25;5(9):eaaw6671. doi: https://doi.org/10.1126/sciadv.aaw6671

McGowen, M. R., Gatesy, J., & Wildman, D. E. (2014). Molecular evolution tracks macroevolutionary transitions in Cetacea. Trends in Ecology & Evolution, 29(6), 336–346. https://doi.org/10.1016/j.tree.2014.04.001

Espregueira Themudo G, Alves LQ, Machado AM, Lopes-Marques M, da Fonseca RR, Fonseca M, Ruivo R and Castro LFC (2020) Losing Genes: The Evolutionary Remodeling of Cetacea Skin. Front. Mar. Sci. 7:592375. DOI: http://doi.org/10.3389/fmars.2020.592375

Hecker, N., Sharma, V., & Hiller, M. (2017). Transition to an Aquatic Habitat Permitted the Repeated Loss of the Pleiotropic KLK8 Gene in Mammals. Genome biology and evolution, vol. 9, no.11 , 3179–3188. https://doi.org/10.1093/gbe/evx239

Mascetti G. (2016). Unihemispheric sleep and asymmetrical sleep: behavioral, neurophysiological, and functional perspectives. Nature and science of sleep, vol. 8, 221–238.    DOI: https://doi.org/10.2147/NSS.S71970

Spaulding, M., O’Leary, M. A., & Gatesy, J. (2009). Relationships of Cetacea (Artiodactyla) Among Mammals: Increased Taxon Sampling Alters Interpretations of Key Fossils and Character Evolution. PLoS ONE, 4(9), e7062. DOI: https://doi.org/10.1371/journal.pone.0007062