F Rosa Rubicondior: Unintelligent Design - How The Same Function Evolved Twice - Once in Vertebrates And Again in Insects

Monday 26 February 2024

Unintelligent Design - How The Same Function Evolved Twice - Once in Vertebrates And Again in Insects

Diagram of an insect compound eye.

UC Irvine study shows similarities and differences in human and insect vision formation – UCI News

Regardless of the different structures in the compound eyes of insects and the eyes of vertebrates, at the heart of them both is a light-sensitive molecule, 11-cis-retinal, also known as 'visual Chromophore', but these are produced in two different ways from the same starting compound - β-carotene - which in humans is obtained from eating plants like carrots which are rich in Vitamin A from which β-carotene is derived.

This is one of those examples which are so common in biology, of where, had it been intelligent, the same designer could have used a process it had designed earlier but did not, instead it designed an even more complex way of doing the same thing, giving the lie to claims that the same 'intelligent' designer designed living things, insects and vertebrates have two different ways to achieve the same product - 11-cis-retinal; the second being the more complicated of the two.

Although the earliest vertebrates appeared about 518 million years ago, so predating the first insects by about 130 million years, the creationists dogma of omniscience which they traditionally ascribe to their putative designer god, would mean this alleged designer was already aware of the less complex way to make 11-cis-retinal, when if supposedly designed the vertebrate method.

Besides, creationist dogma also says they were all created on the same day - 10,000 years ago.

What is the role of 11-cis-retinal (visual chromophore) and how is it produced in vertebrates and insects? 11-cis-retinal, also known as visual chromophore, plays a crucial role in the visual system of both vertebrates and insects as it is a key component of visual pigments, such as rhodopsin in vertebrates and opsins in insects. These pigments are located in the photoreceptor cells of the retina in vertebrates and in the compound eyes of insects, where they are responsible for the initial steps of light detection and signal transduction.

The role of 11-cis-retinal can be summarized as follows:
  1. Light Absorption: When 11-cis-retinal absorbs a photon of light, it undergoes a conformational change to its all-trans form, triggering a series of molecular events that lead to the generation of electrical signals in photoreceptor cells.
  2. Signal Transduction: The conformational change of 11-cis-retinal upon light absorption activates the associated opsin protein, initiating a cascade of biochemical reactions that ultimately result in changes in the membrane potential of the photoreceptor cell. This change in membrane potential forms the basis of visual signal transduction.
In vertebrates, 11-cis-retinal is produced through a series of enzymatic reactions known as the visual cycle, which takes place in the retinal pigment epithelium (RPE) and Müller cells. The visual cycle involves the conversion of all-trans-retinol, obtained from the bloodstream or recycled from photoreceptor cells, to 11-cis-retinal. This process requires several enzymes, including retinol dehydrogenases and isomerohydrolases.

In insects, the biosynthesis of 11-cis-retinal is somewhat different. In the compound eyes of insects, 11-cis-retinal is typically produced through a pathway involving the conversion of dietary carotenoids into retinoids. These retinoids are then converted into 11-cis-retinal through a series of enzymatic reactions occurring in the pigment cells surrounding the photoreceptor cells.

Overall, the production and utilization of 11-cis-retinal are fundamental for the visual systems of both vertebrates and insects, allowing them to detect and respond to light stimuli in their environment.

How the processes differ is the subject of research by five scientists from the Department of Physiology and Biophysics, University of California Irvine School of Medicine, Irvine (UCI), CA, USA who have published their findings open access in the journalNature Chemical Biology. Their work is also explained in a UCI news release:
Researchers at the University of California, Irvine have discovered profound similarities and surprising differences between humans and insects in the production of the critical light-absorbing molecule of the retina, 11-cis-retinal, also known as the “visual chromophore.” The findings deepen understanding of how mutations in the RPE65 enzyme cause retinal diseases, especially Leber congenital amaurosis, a devastating childhood blinding disease. For the study, recently published online in the journal Nature Chemical Biology, the team used X-ray crystallography to study NinaB, a protein found in insects that functions similarly to the RPE65 protein found in humans. Both are crucial for synthesis of 11-cis-retinal, and their absence results in severe visual impairment.

Our study challenges traditional assumptions about the similarities and differences of human and insect vision. While these enzymes share a common evolutionary origin and three-dimensional architecture, we found that the process by which they produce 11-cis-retinal is distinct.

Associate Professor Philip D. Kiser, corresponding author
Professor of physiology & biophysics as well as ophthalmology
Department of Physiology and Biophysics
University of California Irvine School of Medicine, Irvine, CA, USA
Creation of 11-cis-retinal begins with the consumption of foods like carrots or pumpkins containing compounds used for vitamin A generation, such as beta-carotene. These nutrients are metabolized by carotenoid cleavage enzymes, including NinaB and RPE65. It was previously known that humans require two of these enzymes to produce 11-cis-retinal from beta-carotene, whereas insects can achieve the conversion with just NinaB. Gaining insight into how NinaB can couple the two steps into a single reaction along with the functional relationships between NinaB and RPE65 was a key motivation for the study.

We found that structurally, these enzymes are very much alike, but the locations in which they perform their activity are different. Understanding key features within the NinaB structure has led to an enhanced understanding of the catalytic machinery necessary to support the function of the retinal visual pigments. Through our study of NinaB, we were able to learn about the structure of a key portion of RPE65 that had not previously been resolved. This discovery is vital in understanding and addressing loss-of-function mutations in RPE65.

Yasmeen J. Solano, lead author
Department of Physiology and Biophysics
University of California Irvine School of Medicine, Irvine, CA, USA
Other team members included Michael Everett, a junior specialist in the Kiser lab, and Kelly Dang and Jude Abueg, biological sciences undergraduates at the time.
Technical detail and background are given in the team's open access paper:

The retinal light response in animals originates from the photoisomerization of an opsin-coupled 11-cis-retinaldehyde chromophore. This visual chromophore is enzymatically produced through the action of carotenoid cleavage dioxygenases. Vertebrates require two carotenoid cleavage dioxygenases, β-carotene oxygenase 1 and retinal pigment epithelium 65 (RPE65), to form 11-cis-retinaldehyde from carotenoid substrates, whereas invertebrates such as insects use a single enzyme known as Neither Inactivation Nor Afterpotential B (NinaB). RPE65 and NinaB couple trans–cis isomerization with hydrolysis and oxygenation, respectively, but the mechanistic relationship of their isomerase activities remains unknown. Here we report the structure of NinaB, revealing details of its active site architecture and mode of membrane binding. Structure-guided mutagenesis studies identify a residue cluster deep within the NinaB substrate-binding cleft that controls its isomerization activity. Our data demonstrate that isomerization activity is mediated by distinct active site regions in NinaB and RPE65—an evolutionary convergence that deepens our understanding of visual system diversity.

Image-forming vision in animals starts with the photoisomerization of an opsin-linked 11-cis-retinaldehyde (11-cis-RAL) chromophore to an all-trans configuration1. This stereochemical alteration causes conformational changes in the opsin transmembrane helical bundle allowing G protein signaling and the start of phototransduction2,3. These events initiate electrochemical signals within retinal photoreceptor cells that are relayed to the brain through higher order neurons for interpretation. Although specific properties of the visual opsins and the modes of signaling they employ vary among animal groups4, the involvement of an 11-cis-retinoid functioning as the visual chromophore to initiate light perception is universal. In most animal groups, 11-cis-RAL itself is used as the visual chromophore, whereas certain fish and arthropods employ desaturated or hydroxylated 11-cis-RAL derivatives in their visual systems5,6.

Retinaldehyde (RAL) is biosynthetically generated by the oxidative cleavage of dietary carotenoid precursors, which are polyenes with multiple potentially reactive sites7,8. Additionally, 11-cis-RAL is a high-energy retinoid isomer that constitutes an inconspicuous percentage of total RAL at thermal equilibrium9. Ensuring the specificity of both RAL formation from carotenoids as well as its isomerization to the 11-cis configuration necessitates the involvement of enzymes. Iron-dependent, membrane-associated enzymes encompassed within the carotenoid cleavage dioxygenase (CCD) superfamily are pivotal in these biosynthetic transformations7. In vertebrates, β-carotene oxygenase 1 (BCO1) cleaves provitamin A carotenoids symmetrically to yield one or two molecules of all-trans-RAL. RAL is reduced to all-trans-retinol (vitamin A), which is trafficked to the retinal pigment epithelium (RPE) and enters the visual cycle metabolic pathway10,11. This pathway involves another CCD superfamily member known as RPE65, which converts all-trans-retinyl esters into 11-cis-retinol through a coupled ester hydrolysis and C11–C12 alkene isomerization reaction12,13. Previous biochemical and structural studies identified critical active site features in RPE65 responsible for retinoid trans–cis isomerase activity and ester bond hydrolysis which, together with isotope labeling data, allowed the proposal of an isomerohydrolase catalytic mechanism14,15,16,17.

In contrast to the multiple CCD paralogs found in vertebrates, most insect genomes encode a single CCD known as Neither Inactivation Nor Afterpotential B (NinaB)18. The Drosophila melanogaster NinaB ortholog was the initial animal CCD to be cloned and was shown to catalyze the symmetric cleavage of β-carotene to form RAL19,20. Later studies demonstrated that NinaB not only cleaves carotenoids symmetrically but also isomerizes one-half of its substrate to form a ~1:1 mixture of 11-cis and all-trans RAL products21. This enzyme was thus termed an isomerooxygenase.

It is intriguing that two homologous enzymes catalyzing distinct primary chemistry on disparate substrates—retinyl ester hydrolysis in the case of RPE65 and carotenoid oxygenation in the case of NinaB—both possess the ability to catalyze trans–cis isomerization at a C11–C12 retinoid/carotenoid double bond. This finding raises the question of whether the common ancestor of the lineages leading to the NinaB and RPE65 proteins, which existed greater than 550 million years ago22, also possessed trans–cis isomerase activity as previously suggested21,23. If true, the catalytic machinery responsible for isomerase activity in RPE65 and NinaB is expected to be conserved. Indeed, some residues of known importance for RPE65 isomerase activity align with identical residues in NinaB23. Alternatively, isomerase activity may have arisen independently in the two lineages given the fundamental differences in their primary enzymatic activities. Distinguishing between these two possibilities has important implications for our understanding of the early evolution of visual opsins in animals and the mechanisms available for the regeneration of their visual chromophores. The lack of activity data on CCDs from early branching protostomes and deuterostomes precludes phylogenetic and ancestral character state reconstruction approaches to addressing the question. The more direct route of comparing mechanistic relationships between RPE65 and NinaB has been hampered by a paucity of knowledge regarding the structure of the NinaB catalytic site.

To bridge this gap in understanding, we report a high-resolution crystal structure of NinaB from the cabbage looper (Trichoplusia ni), revealing the molecular architecture of its active site and details of its membrane-interacting structural elements. Employing a structure-guided mutagenesis approach, we pinpoint the site responsible for NinaB isomerase activity within its expansive substrate-binding cleft. Comparison with the site of isomerization known for RPE65 indicates a functional convergence in the evolution of CCD isomerase activity for visual chromophore biosynthesis.
Fig. 1: Enzymatic activity of TnNinaB toward carotenoid and xanthophyll substrates.
a, NinaB isomerooxygenases found in insects (represented by the moth silhouette) cleave β-carotene (1) to generate all-trans-RAL (2) and the visual chromophore 11-cis-RAL (3). In vertebrates (represented by the human silhouette), 11-cis-RAL biosynthesis requires two separate CCD enzymes (BCO1 and RPE65). b, HPLC chromatograms demonstrating that TnNinaB displays isomerooxygenase activity toward β-carotene. c, Schematic of NinaB activity towards zeaxanthin (4) generating (3R)-3-hydroxy-all-trans-RAL (5) and (3R)-3-hydroxy-11-cis-RAL (6), the latter serving as the visual chromophore in insects. d, HPLC chromatograms demonstrating that TnNinaB displays isomerooxygenase activity toward zeaxanthin. e, Schematic of NinaB activity toward the asymmetric xanthophyll, lutein (7), generating (3R,6R)-3-hydroxy-all-trans-α-RAL (8) and (3R)-3-hydroxy-11-cis-RAL (6). f, HPLC chromatograms demonstrating that TnNinaB displays isomerooxygenase activity toward lutein. BSA was used as a negative control for the assays. RAL products were converted into oxime derivatives before HPLC analysis, which is indicated by asterisks next to compound numbers in b, d and f. Chromatograms were recorded at a wavelength of 360 nm. Insets in b, d and f show absorbance spectra for each of the labeled peaks confirming their identities. Numbers above spectral maxima are in nanometers. The data are representative of three replicates.

Source data.

Not only do we have, according to creationists, two different designs of eye; we also have two different metabolic pathways for making one of the essential component molecules on which both designs depend, one needlessly more complex than the other.

This is, of course, another example of convergent evolution in which the mindless natural 'design' process has neither foresight not hindsight and no way to copy a successful method evolved in one branch of the evolutionary tree to a different, distant branch, even though it is for doing the same thing.

This is how we can tell, by looking beneath the superficial resemblance of design, that there was no intelligence involved. Only by ignoring the detail and concentrating on the superficial ("Look at the trees!") can creationists maintain the delusion of an intelligent designer.

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