RNA-based evolution

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RNA-based evolution is a theory that posits that RNA is not merely an intermediate between Watson and Crick model of the DNA molecule and proteins, but rather a far more dynamic and independent role-player in determining phenotype. By regulating the transcription in DNA sequences, the stability of RNA, and the capability of messenger RNA to be translated, RNA processing events allow for a diverse array of proteins to be synthesized from a single gene. Since RNA processing is heritable, it is subject to natural selection suggested by Darwin and contributes to the evolution and diversity of most eukaryotic organisms.

Contents

Role of RNA in conventional evolution

In accordance with the central dogma of molecular biology, RNA passes information between the DNA of a genome and the proteins expressed within an organism. [1] Therefore, from an evolutionary standpoint, a mutation within the DNA bases results in an alteration of the RNA transcripts, which in turn leads to a direct difference in phenotype. RNA is also believed to have been the genetic material of the first life on Earth. The role of RNA in the origin of life is best supported by the ease of forming RNA from basic chemical building blocks (such as amino acids, sugars, and hydroxyl acids) that were likely present 4 billion years ago. [2] [3] Molecules of RNA have also been shown to effectively self-replicate, catalyze basic reactions, and store heritable information. [4] [5] As life progressed and evolved over time only DNA, which is much more chemically stable than RNA, could support large genomes and eventually took over the role as the major carrier of genetic information. [6]

Single-Stranded RNA can fold into complex structures

Single-stranded RNA molecules can single handedly fold into complex structures. The molecules fold into secondary and tertiary structures by intramolecular base pairing. [7] There is a fine dynamic of disorder and order that facilitate an efficient structure formation. RNA strands form complementary base pairs. These complementary strands of RNA base pair with another strand, which results in a three-dimensional shape from the paired strands folding in on itself. The formation of the secondary structure results from base pairing by hydrogen bonds between the strands, while tertiary structure results from folding of the RNA. The three-dimensional structure consists of grooves and helices. [8] The formation of these complex structure gives reason to suspect that early life could have formed by RNA.

Variability of RNA processing

Research within the past decade has shown that strands of RNA are not merely transcribed from regions of DNA and translated into proteins. Rather RNA has retained some of its former independence from DNA and is subject to a network of processing events that alter the protein expression from that bounded by just the genomic DNA. [9] Processing of RNA influences protein expression by managing the transcription of DNA sequences, the stability of RNA, and the translation of messenger RNA.

Alternative splicing

Splicing is the process by which non-coding regions of RNA are removed. The number and combination of splicing events varies greatly based on differences in transcript sequence and environmental factors. Variation in phenotype caused by alternative splicing is best seen in the sex determination of D. melanogaster . The Tra gene, determinant of sex, in male flies becomes truncated as splicing events fail to remove a stop codon that controls the length of the RNA molecule. In others the stop signal is retained within the final RNA molecule and a functional Tra protein is produced resulting in the female phenotype. [10] Thus, alternative RNA splicing events allow differential phenotypes, regardless of the identity of the coding DNA sequence.

RNA stability

Phenotype may also be determined by the number of RNA molecules, as more RNA transcripts lead to a greater expression of protein. Short tails of repetitive nucleic acids are often added to the ends of RNA molecules in order to prevent degradation, effectively increasing the number of RNA strands able to be translated into protein. [11] During mammalian liver regeneration RNA molecules of growth factors increase in number due to the addition of signaling tails. [12] With more transcripts present the growth factors are produced at a higher rate, aiding the rebuilding process of the organ.

RNA silencing

Silencing of RNA occurs when double stranded RNA molecules are processed by a series of enzymatic reactions, resulting in RNA fragments that degrade complementary RNA sequences. [13] [14] By degrading transcripts, a lower amount of protein products are translated and the phenotype is altered by yet another RNA processing event.

RNA and Protein

In Earth's early developmental history RNA was the primary substance of life. RNA served as a blueprint for genetic material and was the catalyst to multiply said blueprint. Currently RNA acts by forming proteins. protein enzymes carry out catalytic reactions. RNAs are critical in gene expression and that gene expression depends on mRNA, rRNA, and tRNA. [15] There is a relationship between protein and RNAs. This relationship could suggest that there is a mutual transfer of energy or information. [16] In vitro RNA selection experiments have produced RNA that bind tightly to amino acids. It has been shown that the amino acids recognized by the RNA nucleotide sequences had a disproportionately high frequency of codons for said amino acids. There is a possibility that the direct association of amino acids containing specific RNA sequences yielded a limited genetic code. [17]

Evolutionary mechanism

Most RNA processing events work in concert with one another and produce networks of regulating processes that allow a greater variety of proteins to be expressed than those strictly directed by the genome. [9] These RNA processing events can also be passed on from generation to generation via reverse transcription into the genome. [9] [18] Over time, RNA networks that produce the fittest phenotypes will be more likely to be maintained in a population, contributing to evolution. Studies have shown that RNA processing events have especially been critical with the fast phenotypic evolution of vertebrates—large jumps in phenotype explained by changes in RNA processing events. [19] Human genome searches have also revealed RNA processing events that have provided significant “sequence space for more variability”. [20] On the whole, RNA processing expands the possible phenotypes of a given genotype and contributes to the evolution and diversity of life.

RNA virus evolution

RNA virus evolution appears to be facilitated by a high mutation rate caused by the lack of a proofreading mechanism during viral genome replication. [21] In addition to mutation, RNA virus evolution is also facilitated by genetic recombination. [21] Genetic recombination can occur when at least two RNA viral genomes are present in the same host cell and has been studies in numerous RNA viruses. [22] RNA recombination appears to be a major driving force in viral evolution among Picornaviridae ((+)ssRNA) (e.g. poliovirus). [23] In the Retroviridae ((+)ssRNA)(e.g. HIV), damage in the RNA genome appears to be avoided during reverse transcription by strand switching, a form of genetic recombination. [24] [25] [26] Recombination also occurs in the Coronaviridae ((+)ssRNA) (e.g. SARS). [27] Recombination in RNA viruses appears to be an adaptation for coping with genome damage. [22] Recombination can occur infrequently between animal viruses of the same species but of divergent lineages. The resulting recombinant viruses may sometimes cause an outbreak of infection in humans. [27]

See also

Related Research Articles

<span class="mw-page-title-main">DNA</span> Molecule that carries genetic information

Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

<span class="mw-page-title-main">Genetics</span> Science of genes, heredity, and variation in living organisms

Genetics is the study of genes, genetic variation, and heredity in organisms. It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.

<span class="mw-page-title-main">Nucleic acid</span> Class of large biomolecules essential to all known life

Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is deoxyribose, a variant of ribose, the polymer is DNA.

<span class="mw-page-title-main">Protein biosynthesis</span> Assembly of proteins inside biological cells

Protein biosynthesis is a core biological process, occurring inside cells, balancing the loss of cellular proteins through the production of new proteins. Proteins perform a number of critical functions as enzymes, structural proteins or hormones. Protein synthesis is a very similar process for both prokaryotes and eukaryotes but there are some distinct differences.

<span class="mw-page-title-main">RNA</span> Family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

<span class="mw-page-title-main">Central dogma of molecular biology</span> Explanation of the flow of genetic information within a biological system

The central dogma of molecular biology is an explanation of the flow of genetic information within a biological system. It is often stated as "DNA makes RNA, and RNA makes protein", although this is not its original meaning. It was first stated by Francis Crick in 1957, then published in 1958:

The Central Dogma. This states that once "information" has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information here means the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.

<span class="mw-page-title-main">Genetic recombination</span> Production of offspring with combinations of traits that differ from those found in either parent

Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.

<span class="mw-page-title-main">Gene expression</span> Conversion of a genes sequence into a mature gene product or products

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, and ultimately affect a phenotype. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. The process of gene expression is used by all known life—eukaryotes, prokaryotes, and utilized by viruses—to generate the macromolecular machinery for life.

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, the evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for a protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to non-coding regions over different species and time periods can provide a significant amount of important information regarding gene organization and evolution of prokaryotes and eukaryotes. This can further assist in mapping the human genome and developing gene therapy.

<span class="mw-page-title-main">Molecular genetics</span> Scientific study of genes at the molecular level

Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens. 

<span class="mw-page-title-main">Helicase</span> Class of enzymes to unpack an organisms genes

Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two hybridized nucleic acid strands, using energy from ATP hydrolysis. There are many helicases, representing the great variety of processes in which strand separation must be catalyzed. Approximately 1% of eukaryotic genes code for helicases.

<span class="mw-page-title-main">Silent mutation</span> DNA mutation with no observable effect on an organisms phenotype

Silent mutations are mutations in DNA that do not have an observable effect on the organism's phenotype. They are a specific type of neutral mutation. The phrase silent mutation is often used interchangeably with the phrase synonymous mutation; however, synonymous mutations are not always silent, nor vice versa. Synonymous mutations can affect transcription, splicing, mRNA transport, and translation, any of which could alter phenotype, rendering the synonymous mutation non-silent. The substrate specificity of the tRNA to the rare codon can affect the timing of translation, and in turn the co-translational folding of the protein. This is reflected in the codon usage bias that is observed in many species. Mutations that cause the altered codon to produce an amino acid with similar functionality are often classified as silent; if the properties of the amino acid are conserved, this mutation does not usually significantly affect protein function.

<span class="mw-page-title-main">Nucleoprotein</span> Type of protein

Nucleoproteins are proteins conjugated with nucleic acids. Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.

<span class="mw-page-title-main">Homologous recombination</span> Genetic recombination between identical or highly similar strands of genetic material

Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids.

<span class="mw-page-title-main">Gene</span> Sequence of DNA or RNA that codes for an RNA or protein product

In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA, that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes.

In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, sense may have slightly different meanings. For example, the negative-sense strand of DNA is equivalent to the template strand, whereas the positive-sense strand is the non-template strand whose nucleotide sequence is equivalent to the sequence of the mRNA transcript.

Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.

This glossary of cellular and molecular biology is a list of definitions of terms and concepts commonly used in the study of cell biology, molecular biology, and related disciplines, including genetics, biochemistry, and microbiology. It is split across two articles:

This glossary of cellular and molecular biology is a list of definitions of terms and concepts commonly used in the study of cell biology, molecular biology, and related disciplines, including genetics, biochemistry, and microbiology. It is split across two articles:

References

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