Proteins and their Evolution

Dr.Amresh Sharma
Department of Bioinformatics
Kalinga University Raipur
Proteins are, complex molecules, generally large in size, and are essential for various biological functions within organisms. Made up of amino acids, they form the life’s building blocks, also playing a key role within cells for maintaining its structure, function, and regulation. Proteins participate in virtually every biological process, from enzyme activity to muscle contraction, cellular signaling, and immune responses [1].
Structure of Proteins
Proteins consist of long chains of amino acids arranged in unique sequences, which determine their structure and function. There are 20 standard amino acids, and they are arranged in order and linked to dictates a protein’s unique 3-D shape, or conformation. This structure is critical because it directly influences the protein’s role within the cell. Proteins have four structural levels:
Primary (10) structure: The linear arrangement of sequence of amino acids forming a polypeptide chain.
Secondary (20) structure: Localized patterns causing folding, to form structures such as alpha helices and beta sheets, which is stabilized by hydrogen bonds.
Tertiary (30) structure: The complete 3-dimensional shape of an arranged single polypeptide chain, stabilized by various bonding or interactions among amino acids.
Quaternary (40) structure: It forms when multiple polypeptide chains arranged into a larger complex (if applicable) f Proteins. Proteins serve diverse functions based on their structure. Some key roles include:
Importance
Proteins are essential in human diets, as they provide the amino acids needed for growth, repair, and maintenance of body tissues. Complete proteins, often found in animal sources, provide all essential amino acids, whereas many plant proteins are incomplete on their own but can be combined with other plant sources to form a complete amino acid profile [2,3].
Protein’s Evolution
The evolution of proteins is the process driven by genetic variations that have accumulated over billions of years, allowing proteins to diversify and specialize in response to environmental pressures. This process entails the gradual alteration of genes involve in protein-coding, resulting in new functions of the proteins and its adaptations that are crucial for survival. Here’s a look at how proteins have evolved, with examples to illustrate key concepts [4].
Mechanisms of Protein Evolution
Gene Duplication and Divergence Gene duplication is a major evolutionary mechanism where a gene is copied in the genome. Over time, one copy of a duplicated gene may acquire mutations that change its function, while the other copy continues to perform its original role. This process allows new proteins with novel functions to evolve without losing the original protein’s role [5].
Example: The evolution of the oxygen-carrying proteins, myoglobin and hemoglobin, from a common ancestral globin protein. Initially, gene duplication created two similar genes, which diverged over time. Myoglobin evolved to store oxygen in muscle tissue, while hemoglobin adapted to transport oxygen in blood, showing how gene duplication can lead to functionally distinct proteinsxon Shuffling. Exons are segments of genes that code for specific domains within proteins. Through a process called exon shuffling, exons from different genes can combine, leading to new proteins with combined functional domains.
Example: Tissue plasminogen activator (tPA), a protein involved in blood clot breakdown, is thought to have evolved through exon shuffling. It contains multiple domains found in other proteins, which likely originated from combining exons from different ancestral genes.
Mutations and Natural Selection Point mutations—changes in single nucleotides—can subtly alter protein structure and function. Mutations that improve protein function or stability in a given environment tend to be preserved by natural selection [6].
Example: In polar bear populations, an alteration in the gene that is coding for apolipoprotein B (ApoB), a protein involved in fat metabolism, helps them manage a diet high in fats, aiding survival in Arctic conditions.
Domain Acd Fusion Many proteins consist of modular domains, each with specific functions. Domain accretion, or the addition of new domains to a protein, allows it to acquire new capabilities. Domains from separate proteins can also fuse, creating multifunctional proteins [7].
Example: The protein kinase family, involved in cell signaling, evolved by fusing kinase domains with other functional regions, such as those that bind DNA or anchor the protein to cell membranes. This modular evolution enables kinases to participate in a wide range of cellular processes.
Abiotic Availability of Amino Acids on Primitive Earth: It is believed that amino acids were synthesized abiotically on primitive Earth, creating the essential precursors for the evolution of proteins. This hypothesis is supported by experimental work such as the famous experiment of Miller-Urey, which showed that amino acids could form under conditions similar to those of the prebiotic Earth [8,9].
Evolution of Peptides and RNA in Co-evolution manner: Research has suggested that peptides and RNA may have co-evolved, influencing each other’s functions and structures [10,11].
Sequence Changes and Functional Evolution: Alterations in protein sequences can result in changes to their structure and function, a principle fundamental to evolutionary biology [12.13].
Fixation and Genetic Drift: The likelihood of a new variant becoming fixed in a population depends on its effect on fitness, with genetic drift playing a role alongside natural selection [14,15].
Sudden Transitions and Evolution of New Protein Features: Complex features, such as new protein folds or allosteric properties, can sometimes arise through a small number of mutations [16,17].
Folding Funnel Model in Protein Structure Evolution: The concept of a folding funnel helps explain how protein structures evolve and stabilize, with fewer folding pathways as the native structure becomes more defined [18,19].
Gene Duplication and Functional Drift in Protein Evolution: Gene duplication allows for the evolution of new functions through functional drift or neofunctionalization [20,21].
Protein family and Its Evolution
A family of protein or most commonly called protein family, is a group of proteins with a shared evolutionary origin and common ancestry. Members of a protein family generally have similar structures and functions, and often share similarities in sequence also that reflect their origin from a common ancestral gene. As proteins evolve, they diverge through mutations, duplications, and other genetic modifications, which leads to the creation of distinct but related protein families [22].
Evolution of Protein Families
The evolution of protein families is largely driven by three main processes:
Gene Duplication and Divergence: Gene duplication provides an essential pathway for protein family evolution. Gene duplication produces two copies of the same gene, enabling one copy to maintain its original function while the other can accumulate mutations. Over time, this can lead to functional diversification.
Example: The globin family (including hemoglobin and myoglobin) evolved through gene duplication. The ancestral globin gene duplicated multiple times, and each copy acquired different mutations, leading to proteins with distinct but related functions—such as myoglobin, which stores oxygen in muscle tissue, and hemoglobin, which transports oxygen in blood [23].
Domain Shuffling and Exon Shuffling: Protein evolution often involves the rearrangement of domains, which are discrete functional units within proteins. Through exon shuffling (recombination of exons within genes) or domain accretion (addition of new domains), proteins can acquire new functionalities and evolve into new family members.
Example: The immunoglobulin (Ig) superfamily is an example of a large protein family that diversified through domain shuffling. Ig proteins are involved in immune response, with domains that can vary to recognize different antigens. This shuffling creates diversity that is crucial for adaptive immunity [24].
Convergent and Divergent Evolution: Divergent evolution occurs when proteins from a common ancestor evolve distinct functions over time, creating different subfamilies within the original family. Convergent evolution, though less common in protein families, happens when unrelated proteins independently evolve similar functions.
Example: Serine proteases, enzymes that cut peptide bonds in proteins, represent a classic case of divergent evolution. This family includes enzymes such as trypsin, chymotrypsin, and elastase, which evolved to work on different substrates but retain similar catalytic mechanisms.
Types of Protein Families and Evolutionary Patterns
Orthologs and Paralogs
Orthologs are proteins found in different species that have evolved from a shared ancestral protein and typically maintain the same function across species. For example, the Hb genes (haemoglobin) genes in humans and chimp are orthologs.
Paralogs are proteins within the same species that arose from gene duplication and have since evolved to perform related, but often distinct, functions. For instance, in humans, hemoglobin and myoglobin are paralogs with distinct roles in oxygen transport and storage, respectively.
Superfamilies
Superfamilies include distantly related proteins that may have less sequence similarity but share structural motifs or domains. These superfamilies often arise through multiple rounds of duplication and divergent evolution, as well as domain shuffling.
Example: The superfamily of G-protein coupled receptor (GPCR) includes receptors involved in diverse cellular signaling processes. Despite their functional diversity, GPCRs share a characteristic seven-transmembrane domain structure [25].
Achievements related Protein Evolution
In 2018, the Nobel Prize in Chemistry was awarded to Frances Arnold for her pioneering work on the “directed evolution of enzymes,” a process that mimics natural evolution in the lab to create proteins with desired characteristics. By generating random mutations in protein-encoding genes and selecting for enzymes with improved properties, her work has significantly advanced the field of protein engineering. This approach allows scientists to create proteins with enhanced catalytic abilities, better stability, and adaptability to various chemical processes, leading to applications in green chemistry, biofuels, and pharmaceuticals. Arnold’s work demonstrated how evolutionary techniques could be applied to improve proteins’ functional characteristics, showcasing a powerful method for exploring how proteins evolve. This breakthrough has had extensive implications for our understanding of enzyme function, stability, and adaptability, expanding the possibilities for biotechnological applications. Her contributions have also provided deeper insights into how proteins can evolve new functions, showing that through a few targeted mutations, proteins can gain novel catalytic activities. The prize was jointly awarded to George P. Smith and Sir Gregory Winter in the same year for their development of phage display technology, which enables the rapid generation and selection of proteins with high specificity for their targets. This technology has become a crucial tool in antibody drug development [26-29].
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