20 May 2024
Eben van Tonder

Introduction

In a fascinating lecture presented by the Royal Institution of Great Britain, Philip Ball. Philip is a freelance writer and broadcaster and was an editor at Nature for more than twenty years. He takes us on an intriguing journey through the complexities of the human genome, comparing it to a musical score.

The segment is titled “Turning the Genome into Music.” He explores the disordered nature of our genetic building blocks.  Recent discoveries challenge our traditional understanding of genes and their roles, exposing the dynamic and intricate nature of genetic information. I became intensely interested in the subject while reviewing the history of our understanding of the structure and function of proteins which is our main subject in the field of meat science.

Understanding the latest thinking on the role of DNA, RNA and proteins has profound implications, not only for human biology but also for fields such as meat science.

Section A: Insights from Philip Ball’s Lecture

“Possibly as few as 20,000 genes and by some estimates as little as 19,000 code proteins. Did we have the wrong idea of what role genes were playing? In the 1990s, there were one or two genes that scientists could not find corresponding proteins for, and in the end, they had to conclude that there weren’t any. These genes simply make RNA, not the messenger RNA that gets translated by the ribosome into a protein. In this case, the RNA is the end in itself. It has some biochemical functions. It does the kind of thing that we thought proteins do. These RNA-encoding genes are called non-coding genes. Not because they don’t code anything, but because they don’t encode proteins, which is what we thought – we thought all genes encode proteins” (Philip Ball).

Over the past few decades, the discovery of non-coding RNA (ncRNA) has transformed our understanding of genetic functionality. These RNAs perform various biochemical tasks within the cell which we traditionally attributed to proteins. This revelation has broadened our comprehension of genetic regulation and its impact on cellular processes.

“These were not exceptions. Over the past two decades, the number of these non-coding genes kept creeping up. A few years ago, the number of non-coding genes exceeded the genes that code proteins. Current estimates suggest that this trend will continue. It seems that we will find out that non-coding genes vastly outnumber protein-coding genes” (Philip Ball).

The increasing prevalence of non-coding genes underscores the genome’s complexity, demonstrating that ncRNAs are integral to various cellular functions, including gene regulation, genome stability, and chromatin modulation. This insight challenges the simplistic view that genes solely encode proteins.

“The picture is even more transformed. These are only the genes that code the relatively long RNA molecules that qualify as genes. It has been discovered that there are actually lots of other bits of the genome or our genome and also other large animals (called Metazoans) that encode lots of smaller RNA molecules. And there are all these different families with fancy names (housekeeping ncRNAs, regulatory ncRNAs, short ncRNAs, long ncRNAs). They do all kinds of protein-like tasks in the cell. The genome is not really what we thought it was” (Philip Ball).

In addition to long non-coding RNAs (lncRNAs), researchers have identified numerous small non-coding RNAs (sncRNAs) that play critical roles in gene expression regulation, RNA processing, and other cellular functions. These include microRNAs (miRNAs), small interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs). These small RNAs add another layer of regulatory complexity, demonstrating that the genome operates through a vast network of RNA molecules in addition to proteins.

“Crick’s central dogma said that genes encode proteins, and by that, we mean that genes actually program proteins with particular shapes so that they can go and do a specific function. But this picture is now modified. It does not mean that each gene encodes a particular protein. Each of our genes can typically be used to program several different proteins. On average, each can make about six different proteins. Some genes can encode dozens or even hundreds of different proteins. We have many proteins, and no one knows how many, but many more than we have protein-coding genes” (Philip Ball).

The central dogma of molecular biology, proposed by Francis Crick, described the flow of genetic information from DNA to RNA to protein. This concept has evolved with the discovery of alternative splicing, where a single gene can produce multiple protein variants by rearranging its exons during RNA processing. This mechanism significantly expands the proteome’s diversity, allowing organisms to generate a wide array of proteins from a limited number of genes.

“This is because, as we discovered in the 1970s, the messenger RNA that is transcribed from a gene is typically chopped up and edited before it is translated. So, there is another piece of molecular machinery. This thing called the spliceosome, made up of several different proteins, gets hold of the messenger RNA, chops it into different fractions, throws away some pieces called introns, and stitches together the remaining fractions called exons back in various orders. What decides how this splicing and editing occurs is typically information coming from a higher level of the system, for example, from the overall state of the cell in which it’s happening. So, a gene in one tissue may produce one type of protein, and in a different tissue may produce a different protein” (Philip Ball).

The spliceosome’s role in RNA splicing underscores the importance of post-transcriptional modifications in gene expression. The regulation of alternative splicing is influenced by various factors, including the cell’s physiological state and external signals, allowing cells to adapt their protein production to specific needs and conditions. This complexity illustrates the dynamic nature of genetic information flow and its responsiveness to cellular contexts.

“The information flow here isn’t as the central dogma at least implied; it isn’t all from the bottom up, from DNA to RNA to proteins. Some crucial information for making the protein comes from the outside, and this is just one of the ways in which, to build us and to keep us alive all these years, information doesn’t just flow upwards from the genes to higher levels of organization but flows up and down and in between and in all sorts of directions among them. It’s an open information system, not a closed one” (Philip Ball).

The concept of an open information system in genetics highlights the bidirectional and multidirectional nature of genetic regulation. Genetic information is influenced by external signals, environmental factors, and cellular states, which feed back into the genome to modulate gene expression. This interplay between genes and their environment underscores the complexity of biological systems and the integration of multiple layers of regulatory mechanisms.

The analogy of the genome to a musical score beautifully illustrates the balance between order and flexibility in genetic regulation. Intrinsically disordered proteins (IDPs) are a prime example of this flexibility. Unlike structured proteins, IDPs lack a fixed three-dimensional structure, allowing them to interact with multiple targets and participate in various cellular processes. This structural flexibility is particularly advantageous in complex organisms, enabling versatile responses to dynamic cellular environments and facilitating the regulation of intricate biological networks. Evolution has thus favoured the presence of IDPs in multicellular organisms to support their complexity and adaptability.

“And here’s another change to the picture. In the analogy of the genome to a musical score, we might say that the score is what prevents the orchestra from just playing a whole lot of random notes. It tells each musician which note to play and when. It is the equivalent way a protein’s gene’s encoded shape tells it what to do in the cell – which molecules to grab hold of and which to ignore. There was an earlier reference to this lock-and-key aspect, but we now know that for many of our proteins, including some with some of the most important jobs in the cell, the DNA score isn’t like this at all. It’s much more open to interpretation. Some genes encode proteins without assigning them a structure. It leaves them loose and floppy, or as biochemists say, they are intrinsically disordered. This is not a failure of the genome to give genes a proper shape. It is a deliberate feature that evolution had ‘chosen’ because there is much less of this intrinsic disorder among proteins of simpler organisms like bacteria. So, evolution was clearly fine with giving proteins a very specific structure, but it seems that it has found it useful or perhaps even necessary to give proteins disorder in order to make more complex multicellular, multi-tissue organisms like us” (Philip Ball).

Section B: Relevance and Practical Applications in Meat Science

After this fascinating discussion, I solicited the help of AI to list possible applications in the field of neat science.

It would seem that the insights from Philip Ball’s lecture have direct applications in meat science, particularly in understanding meat quality, processing, and preservation. Understanding gene expression, the role of non-coding RNAs (ncRNAs), and the presence of intrinsically disordered proteins (IDPs) can provide valuable information for improving meat quality, optimizing processing techniques, and enhancing preservation methods.

Gene expression and the resulting proteins play crucial roles in determining meat quality, including tenderness, flavour, and colour. For example, the regulation of muscle proteins such as myoglobin impacts meat colour, while enzymes involved in muscle metabolism affect tenderness. Non-coding RNAs can regulate gene expression and influence metabolic pathways in muscle tissue. Understanding the role of ncRNAs can help develop strategies to enhance meat preservation, reduce spoilage, and extend shelf life. IDPs in muscle tissues may influence the structural properties of meat, affecting its texture and response to processing techniques like curing and cooking. Knowledge of IDPs can help optimize processing conditions to achieve desired meat qualities.

All this talk about IDPs made me wonder what the implications are for using brains in processed meats considering the high content of intrinsically disordered proteins (IDPs) in the brain. Here’s how these characteristics relate to potential applications in meat products:

1. High Water Solubility of IDPs: IDPs are highly soluble in water due to their abundant polar and charged amino acids. This characteristic makes them suitable for applications where water absorption and retention are critical. For instance, when considering the utilization of animal brains in meat processing, one could hypothesize using solubilized brain matter as an additive in meat-on-meat injection applications. The solubilized brain proteins could potentially help in enhancing moisture retention in meat products during cooking processes.
2. Behaviour upon Heating: While IDPs are soluble and interact with water, their behaviour when heated is less predictable compared to structured proteins. They might not form stable gels or exhibit strong binding interactions with other proteins when exposed to heat. Therefore, while they can enhance moisture retention due to their hydrophilic nature, their ability to bind structurally to other meat proteins during cooking might be limited.
3. Absence of Heme Groups: Since IDPs in the brain do not contain heme groups, they do not participate in oxygen transport or storage, which are typical functions of heme-containing proteins like myoglobin in muscle tissues. This absence also means that the brain tissue won’t contribute to the colour or flavour profiles typically associated with meat-curing processes, which often rely on reactions involving myoglobin.

Considering these properties, animal brains can be explored as additives in specific meat products where enhanced water retention is desirable. Products such as sausages or injected meats that benefit from higher moisture content could be potential candidates. The solubilized brain matter might be used in a formulation to act as a natural binder or moisture retainer, although it will not function as a typical binder that contributes to the gelation and texture.

Applications in Meat Products:

• Injected Meats: Using solubilized brain as an injection in meats could help maintain moisture during cooking, improving tenderness and perceived juiciness.
• Sausages and Emulsified Products: While brains might not provide binding in the traditional sense, their water-holding capacity could benefit products where fat and water emulsions are critical, potentially aiding in creating a smoother texture.
• Speciality Deli Items: Given their unique origin and biochemical properties, processed brain ingredients could be marketed in speciality or gourmet products where uniqueness and innovation are selling points.

Philip’s discussion on proteins, particularly focusing on intrinsically disordered proteins (IDPs) made me wonder how this knowledge impacts our view on how animals are raised and the impact of the associated quality of meat produced.

Here are a few interesting thoughts.

1. Animal Health and Protein Synthesis:
Understanding proteins, including IDPs, enhances our comprehension of animal health at a molecular level. Proteins are crucial for numerous biological processes, including muscle growth, immune responses, and stress management. IDPs, with their flexible structures and roles in cellular signalling and regulation, are particularly influential in how animals respond to their environments. In free-range systems, animals typically experience less stress and have more opportunities for natural behaviours, which can lead to healthier physiological states. Lower stress levels can affect the synthesis and function of proteins, including IDPs, by reducing the chronic activation of stress response pathways and potentially leading to a more balanced protein expression profile. This balance can enhance immune function, growth rates, and overall health, indirectly contributing to better meat quality.

2. Protein Synthesis and External Factors:
External factors such as diet, exercise, and environmental stressors directly influence the synthesis of proteins in animals. For instance:

• Diet: Nutritional intake affects protein synthesis by providing the necessary amino acids and nutrients required for protein construction. Free-range animals often have access to a more natural and varied diet, which can lead to a more comprehensive nutrient intake, supporting robust protein synthesis and healthier animal development.
• Exercise: Physical activity influences muscle development and overall health. Free-range animals typically have more space and opportunity to move, which promotes better muscle tone and healthier physiological development. This activity influences muscle protein synthesis, potentially leading to leaner and better-textured meat.
• Stress: Chronic stress can lead to the overexpression of stress-related proteins and the suppression of other beneficial proteins, disrupting normal physiological processes. By contrast, animals in less stressful environments, such as free-range conditions, may exhibit a protein expression profile that supports healthier growth and immune function.

3. Implications for Rearing Practices:
With a deeper understanding of how proteins and IDPs function in animals, farmers and meat producers can better tailor animal-rearing practices to optimize health and meat quality. This might include strategies such as:

• Enhancing Diet Quality: Formulating diets that not only meet the nutritional requirements but also support optimal protein synthesis and function.
• Improving Living Conditions: Reducing stress through better living conditions can lead to healthier animals by promoting a more favourable protein expression profile, particularly by reducing the expression of stress-induced proteins.
• Implementing Animal Welfare Practices: Practices that improve animal welfare can lead to healthier animals by maintaining a balanced physiological state, which is reflected in the quality and properties of the proteins synthesized, including IDPs.

Our evolving understanding of proteins, particularly the role and nature of IDPs, significantly impacts how we think about animal rearing. By acknowledging how external factors influence protein synthesis, the industry can develop strategies that enhance animal health and improve meat quality, aligning with consumer preferences for animal welfare and product excellence.

Conclusion

The insights from Philip’s discussion on intrinsically disordered proteins (IDPs) and considering their roles in animal biology offer implications for meat science, particularly in how we approach animal rearing and meat production. I also find the discussion on the use of the brain fascinating!

Understanding the roles that proteins, especially IDPs, play in cellular regulation, stress response, and overall animal health provides an appreciation of the biological processes influenced by rearing conditions and the look at the characteristics of IDPs informs its possible role in meat formulations. 

As we integrate this knowledge into meat production practices, it becomes evident that factors like diet, exercise, and stress management are not just peripheral concerns but are central to optimizing protein synthesis and function in livestock. This perspective encourages a shift towards rearing practices that prioritize animal welfare and environmental enrichment, which in turn can lead to healthier animals and potentially superior meat quality. Emphasizing less stressful, more natural living conditions in free-range systems may help in achieving these goals, reflecting a more holistic approach to meat science that aligns with emerging consumer preferences and sustainability considerations.

The characteristics of IDPs gave me a greater appreciation for the fact that not all proteins respond the same in, for example, gel formation. Overall, an insightful discussion.