1. Developmental Biology

Evolution: The beat goes on

Why is the alligator heart so similar to the hearts of birds and mammals?
https://doi.org/10.7554/eLife.36882
Share this article
Cite this article
  1. Tobias Wang
(2018)
Evolution: The beat goes on
eLife 7:e36882.
https://doi.org/10.7554/eLife.36882
  2. Download BibTeX
  3. Download .RIS
  1. Tobias Wang  Is a corresponding author
  1. Aarhus University, Denmark

The human heart consists of four chambers – two atria and two ventricles – that expand and contract in order to drive blood containing oxygen and nutrients throughout the body. The atria, which have relatively thin walls, fill first, before squeezing the blood into the much stronger ventricles, which then contract to send blood coursing through our arteries. Most reptiles have two atria and one ventricle. The only exceptions are the 23 living species of crocodilians (alligators, caimans, crocodiles and gharials) who, like birds and mammals, have four-chambered hearts with two atria and two ventricles (Jones, 1996; Jensen et al., 2014).

In vertebrates, each heartbeat is initiated when a pacemaker region in one of the atria generates an electrical signal. The structure and exact location of the pacemaker region differ amongst species (Jensen et al., 2017), but it is always innervated by the autonomic nervous system. This allows the body to increase or decrease the heart rate in response to metabolic demands (Wang, 2012).

The electrical signal from the pacemaker region spreads rapidly across the cardiac muscle cells of the atria via structures called gap junctions, and this ensures that the entire wall of each atrium contracts almost simultaneously. Neurons called Purkinje fibers are also involved in this process in birds but, in general, the mechanisms responsible for the contraction of the atria are similar in most vertebrates. However, the way in which the electrical signal travels from the atrium to the ventricle differs amongst vertebrates, and the evolution of this pathway has been the focus of considerable attention for many decades (Davies, 1942; Jensen et al., 2012, 2013). Now, in eLife, Vincent Christoffels of the University of Amsterdam and colleagues – including Bjarke Jensen and Bastiaan Boukens as joint first authors – report new and surprising findings about this phenomenon in alligators (Jensen et al., 2018).

Back in the 17th century, William Harvey had already noticed that the atria contract before the ventricles in a number of different animals. This meant that the electrical signal generated in the pacemaker region must somehow be slowed down at the 'border' between the atria and the ventricles. In both mammals and birds, a layer of fibrous fatty tissue – which does not conduct electricity – insulates the ventricles from the atria. The only way that the electrical signal can pass from the atria to the ventricles is via a small structure called the atrioventricular node, which is positioned immediately above the septum that separates the left and right ventricles. When the electrical signal reaches this node, it activates two bundles of neurons (containing His fibers and Purkinje fibers) that swiftly relay the impulse and cause the ventricles to contract simultaneously.

However, in extant reptiles, the common ancestor of both birds and mammals, there does not seem to be an insulating layer or an anatomically defined node (Davies, 1942). Instead, the electrical signal is slowed down by an intricate arrangement of myocardial fibers at the junction between the two atria and the ventricle. In addition, recent studies have been unable to provide any anatomical evidence for a conduction system in the ventricle of reptiles. The electrical signal appears to be conveyed by the internal lining of the heart, which shares molecular signatures with the conduction system found in birds and mammals (Jensen et al., 2012).

While reptiles rely on their environment to maintain their temperature (that is, they are ectothermic), mammals produce their own heat (so they are endothermic). The high levels of metabolism needed to produce enough warmth means that the resting and maximal metabolic rates of mammals and birds are about 10 times higher than those of ectothermic animals (Bennett and Ruben, 1979). The cardiovascular system must keep up with these greater needs by delivering more oxygen to the body. The four-chambered heart provides an efficient solution by keeping oxygenated and non-oxygenated blood separate. The supply of oxygen to the body can also be improved by increasing how often the heart contracts. This requires cardiac structures that quickly conduct electricity, such as the atrioventricular nodes (Burggren et al., 2014).

Jensen et al. – who are based in Amsterdam and labs in the United States and the Czech Republic – combine electrophysiology and gene expression techniques to identify how electric impulses spread across the crocodilian heart, and to characterize the molecular phenotype of the various chambers. The experiments provided unequivocal evidence of an atrioventricular node in crocodilians. Among extant reptiles, crocodilians are the closest living sister group to birds. However, despite their four-chambered hearts and an atrioventricular node, all living crocodilians are clearly ectothermic and have low heart rates like other reptiles (Hillman and Hedrick, 2015; Lillywhite et al., 1999; Joyce et al., 2018).

With their ability to walk with their body off the ground, their peculiar respiratory muscles, their avian-like lungs and various other traits, crocodilians may have once been endothermic (Seymour et al., 2004; Hillenius and Ruben, 2004). According to this hypothesis, they switched to ectothermy when they adopted an entirely aquatic life style and became sit-and-wait predators with intermittent meals separated by long fasting periods. However, if past crocodilians had warm blood and some of the associated heart structures, have extant species lost their His and Purkinje fibers? Would these cells – which support high-speed electrical signals – pose functional problems in animals with very low heart rates?

The fact that crocodilians have an atrioventricular node also sheds light on the evolution of the vertebrate heart. For example, the mere presence of a node and a division between the ventricles may be enough to prevent the electrical signal from 're-entering' the atria (which would disrupt the operation of the heart). These findings may also suggest that a nodal structure allows better fine-tuning of the heart rate by the autonomic nervous system.

The next step is to characterize the electrophysiological properties of the cells in the atrioventricular node of crocodilians. Electrocardiogram recordings would also help to understand the exact timing of cardiac events, while flow and pressure measurements would capture the dynamics of the blood flow. There may still be delightful discoveries awaiting us inside the four chambers of the crocodilian heart.

References

    1. Jones DR
    (1996)
    The crocodilian central circulation: reptilian or avian?
    Verhandlungen Der Deutschen Zoologischen 89:209–218.
    1. Lillywhite HB
    2. Zippel KC
    3. Farrell AP
    (1999) Resting and maximal heart rates in ectothermic vertebrates
    Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 124:369–382.
    https://doi.org/10.1016/S1095-6433(99)00129-4
  15. Book
    1. Wang T
    (2012)
    Evolution of the cardiovascular autonomic nervous system in vertebrates
    In: Robertson D, Biaggioni I, Burnstock G, Low P. A, Paton J. F. R, editors. Primer on the Autonomic Nervous System (Third edition). Oxford: Academic Press. pp. 669–674.

Article and author information

Author details

  1. Tobias Wang

    Tobias Wang is in the Department of Zoophysiology, Aarhus University, Denmark, and the Aarhus Institute of Advanced Studies (AIAS) at Aarhus University, Denmark
    For correspondence
    tobias.wang@bios.au.dk
    Competing interests
    No competing interests declared

Publication history

  1. Version of Record published:

Copyright

© 2018, Wang

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 9,207
    views
  • 131
    downloads
  • 0
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Tobias Wang
(2018)
Evolution: The beat goes on
eLife 7:e36882.
https://doi.org/10.7554/eLife.36882

Categories and tags

    1. Related to

    Specialized impulse conduction pathway in the alligator heart

    Bjarke Jensen, Bastiaan J Boukens ... Vincent M Christoffels
  2. Further reading

Further reading

    1. Developmental Biology

    Specialized impulse conduction pathway in the alligator heart

    Bjarke Jensen, Bastiaan J Boukens ... Vincent M Christoffels
    Research Article Updated

    Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles. This system may have evolved together with high heart rates to support their endothermic state (warm-bloodedness) and is seemingly lacking in ectothermic vertebrates from which first mammals then birds independently evolved. Here, we studied the conduction system in crocodiles (Alligator mississippiensis), the only ectothermic vertebrates with a full ventricular septum. We identified homologues of mammalian conduction system markers (Tbx3-Tbx5, Scn5a, Gja5, Nppa-Nppb) and show the presence of a functional atrioventricular bundle. The ventricular Purkinje network, however, was absent and slow ventricular conduction relied on trabecular myocardium, as it does in other ectothermic vertebrates. We propose the evolution of the atrioventricular bundle followed full ventricular septum formation prior to the development of high heart rates and endothermy. In contrast, the evolution of the ventricular Purkinje network is strongly associated with high heart rates and endothermy.

    1. Developmental Biology
    2. Genetics and Genomics

    Determining the effects of paternal obesity on sperm chromatin at histone H3 lysine 4 tri-methylation in relation to the placental transcriptome and cellular composition

    Anne-Sophie Pepin, Patrycja A Jazwiec ... Sarah Kimmins
    Research Article

    Paternal obesity has been implicated in adult-onset metabolic disease in offspring. However, the molecular mechanisms driving these paternal effects and the developmental processes involved remain poorly understood. One underexplored possibility is the role of paternally-induced effects on placenta development and function. To address this, we investigated paternal high-fat diet-induced obesity in relation to sperm histone H3 lysine 4 tri-methylation signatures, the placenta transcriptome and cellular composition. C57BL6/J male mice were fed either a control or high-fat diet for 10 weeks beginning at 6 weeks of age. Males were timed-mated with control-fed C57BL6/J females to generate pregnancies, followed by collection of sperm, and placentas at embryonic day (E)14.5. Chromatin immunoprecipitation targeting histone H3 lysine 4 tri-methylation (H3K4me3) followed by sequencing (ChIP-seq) was performed on sperm to define obesity-associated changes in enrichment. Paternal obesity corresponded with altered sperm H3K4me3 at promoters of genes involved in metabolism and development. Notably, sperm altered H3K4me3 was also localized at placental enhancers. Bulk RNA-sequencing on placentas revealed paternal obesity-associated sex-specific changes in expression of genes involved in hypoxic processes such as angiogenesis, nutrient transport, and imprinted genes, with a subset of deregulated genes showing changes in H3K4me3 in sperm at corresponding promoters. Paternal obesity was also linked to impaired placenta development; specifically, a deconvolution analysis revealed altered trophoblast cell lineage specification. These findings implicate paternal obesity-effects on placenta development and function as one potential developmental route to offspring metabolic disease.

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Modeling corticotroph deficiency with pituitary organoids supports the functional role of NFKB2 in human pituitary differentiation

    Thi Thom Mac, Teddy Fauquier ... Thierry Brue
    Research Article

    Deficient Anterior pituitary with common Variable Immune Deficiency (DAVID) syndrome results from NFKB2 heterozygous mutations, causing adrenocorticotropic hormone deficiency (ACTHD) and primary hypogammaglobulinemia. While NFKB signaling plays a crucial role in the immune system, its connection to endocrine symptoms is unclear. We established a human disease model to investigate the role of NFKB2 in pituitary development by creating pituitary organoids from CRISPR/Cas9-edited human induced pluripotent stem cells (hiPSCs). Introducing homozygous TBX19K146R/K146R missense pathogenic variant in hiPSC, an allele found in congenital isolated ACTHD, led to a strong reduction of corticotrophs number in pituitary organoids. Then, we characterized the development of organoids harboring NFKB2D865G/D865G mutations found in DAVID patients. NFKB2D865G/D865G mutation acted at different levels of development with mutant organoids displaying changes in the expression of genes involved on pituitary progenitor generation (HESX1, PITX1, LHX3), hypothalamic secreted factors (BMP4, FGF8, FGF10), epithelial-to-mesenchymal transition, lineage precursors development (TBX19, POU1F1) and corticotrophs terminal differentiation (PCSK1, POMC), and showed drastic reduction in the number of corticotrophs. Our results provide strong evidence for the direct role of NFKB2 mutations in the endocrine phenotype observed in patients leading to a new classification of a NFKB2 variant of previously unknown clinical significance as pathogenic in pituitary development.