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I have a Computer Science background and a minimal biology knowledge. This is the question I am asked to answer in one of the biology courses:
What would be the structure of ribosomal proteins when isolated from the ribosome?
I do understand (on a high level) what a protein and a ribosome are. I read about the rRNA, ribosomal proteins, 30s and 50s subunits. That gave me an overall insight, but it didn't specifically answer the question. I also tried to Google some pictures of these proteins without much success. Thus, what I want to ask is:
i) What's the concrete answer to this question?
ii) Does the structure of an isolated protein differ to being part of a ribosome?
iii) What exactly do I need to say about its structure? Secondary, Tertiary, something else?
and most importantly
iv) How would a biologist attempt to answer this question?
Origin of the Ribosome Baffles Evolutionists
Figure 1. A diagram of a ribosome showing its enormously complex structure. From Fvoigtsh via WikiCommons.
The ribosome is a macromolecular machine used by all living cells, both prokaryotes like bacteria and eukaryotes, including all vertebrates from fish to humans. The cell requires ribosomes to convert the DNA instructions into the functional proteins that make up all life. A cell cannot survive without ribosomes, each of which contains thousands of parts, all of which must be manufactured and assembled to exacting specifications. Every second of every day, all life’s [or living] cells are making proteins based on the information stored in its DNA. It is for this reason an animal cannot live until all of its billions of parts, including the ribosome, are manufactured and properly assembled. Even though DNA is described as having “massive intelligence . . . by itself [it has] neither a future nor a present. DNA without a cell to sustain and express it has no physiologic meaning.” The structure of the ribosome, which was solved only in the year 2000
revealed that it is still at heart a ribozyme [an RNA molecule capable of acting as an enzyme], with RNA elements still carrying out its essential function, establishing a peptide bond. Why, then, did it grow to such an unwieldy size and incorporate so many proteins into its structure? Real-time observation of its assembly under physiological conditions has some surprising answers.
This feat revealed that the “ribosome is the most complex molecular machine shared by all cellular life forms.… researchers can now study the assembly of the [ribosome] structure in real time, yielding further insights into the origins of complexity” of this machine. And what they are learning has given evolutionists a big headache. As you read this brief description of how the ribosome system produces protein according to the code contained in DNA, it is clear that, first, the system will not function as a ribosome until all of its millions of parts exist and are properly assembled. Then I will explain the failed attempts to explain the evolution of this system that must exist in all living cells.
Human genes are estimated to be, on the average, 40,000 base pairs (bp) long including control sequences and introns. Gene lengths range from 1,480 bp for the somatostatin gene to over 2,000,000 bp for the dystrophin gene. Most genes range from 300 to 3,000 bp. To produce a functional protein, the 20 necessary amino acids must be assembled into the order required to produce polypeptide chains that fold according to the specific amino acid positions on the amino acid chains. The animal body is made up primarily of proteins.
Ribosomal RNA and Ribosomes
Ribosomes are “extremely complex” protein synthesis machines that serve as peptide chain assembly jigs to ensure the proper attachment, alignment, and securement of the amino acid building blocks. The ribosome consists of about 50 proteins and special RNA called ribosomal RNA (rRNA). Ribosomes are differentiated by size their subunit parts designated in terms of solid sedimentation rates. The time it takes for a particle to settle out of solution is measured as a sedimentation coefficient in Svedberg (S) units, where 1S = 10 -13 seconds. Since Svedberg units represent settling rates, and not particle weights, they are not additive. For example, prokaryotic ribosomes use a 70S ribosome made from two parts, a large 50S subunit and a small 30S subunit, whereas eukaryotic ribosomes use the slightly larger 80S type composed of a large 60S and a small 40S subunit. Ribosomes are all metalloenzyme dependent, principally on divalent magnesium (Mg 2+ ion ). The ribosome contains enzymatic proteins and three different sections of RNA that are exactly 120, 1,542 and 2,904 nucleotides long. The structure functions as a frame to control the conversion of the DNA base code into a set of amino acid chains, a process called translation.
The RNA molecule is very similar to the DNA molecule, but has a ribose sugar backbone and uses the uracil base instead of thymine. One type of RNA called messenger RNA (mRNA) carries the code stored on a DNA molecule to the protein manufacturing sites on the ribosomes. The mRNA is usually from about 70 to several thousand nucleotides in length. The half-life of mRNA is only about 1 to 5 minutes, a fact helping to control protein production. Because of this short half-life, about half of all RNA synthesized is mRNA yet it consists of only three percent of cellular RNA at any one time.
Figure 2. A cartoon diagram of the ribosome in action.
DNA length ranges from several thousand to about a billion nucleotides long, depending on the organism. In humans, the total nucleotide length is three billion bp. Bacteria contain several million DNA nucleotides, the simpler eukaryotes such as fungi contain a half billion, and some flowering plants contain several hundred billion.
The ribosome also must find the proper section on mRNA to begin translation. In prokaryotes this site is marked by a set of bases called the Shine-Dalgarno Sequence which is located about ten bases upstream from the initiation site. The initiation site begins at the first subsequent AUG sequence made from the DNA bases Adenine, Uracil and Guanine. The AUG sequence is the start codon but also codes for the amino acid methionine. In eukaryotes, the initiation usually begins at the first AUG sequence on the mRNA, but is a simpler system than used in the prokaryotes the opposite of what evolution predicts! The methionine that AUG codes for usually has to be removed from the polypeptide before the chain is completed.
In prokaryotes, for the ribosome to bind requires three initiation factors labeled IF-1, IF-2 and IF-3. The IF-1 and IF-2 binds to the 30S ribosomal subunit. Then the larger subunit joins and this complex then must bind to a tRNA (transfer RNA) carrying methionine, then bonds to an IF-2 molecule and to the mRNA molecule on the initiation site. The eukaryote system is more complex involving as many as ten or more initiation factors. Lastly, the 50S subunit bonds to the RNA, causing the IF-1, -2 and -3 to fall off.
Figure 3. tRNA showing the yeast eukaryote amino-acid structure and the four arm design when viewed from the top.
The mRNA first attaches to the smaller ribosome subunit, then the first tRNA is matched with the code. Next, the larger ribosome subunit connects to the smaller, and the second tRNA bonds with its matching mRNA code. As the mRNA slides through the ribosome, the tRNA lines up amino acids according to the codon and anticodon match. The anticodon is complementary to one of the codons for the amino acid it carries. The next step requires a tRNA molecule associated with an elongation factor TU protein (EF-TU) to carry its proper amino acid to bind to the ribosome.
Transfer RNA (tRNA)
The tRNA is a single strand of RNA between 73 and 93 nucleotide sections which folds back on itself so that its bases can hydrogen-bond to form the shape required to carry out its role in the cell. Like proteins, the tRNA folds to produce the required three-dimensional shape, and is therefore sometimes humorously said to be an RNA that wanted to be a protein.
The tRNA functions to transfer the amino acids floating nearby to the growing polypeptide chain. A typical eukaryotic cell contains up to 100 different tRNAs, accounting for up to 15 percent of the total cellular RNA by weight. At least twenty tRNAs exist, one for each amino acid. Thus tRNA ala carries only alanine, etc.
The tRNA’s clover leaf secondary structure has four arms plus an acceptor stem. The acceptor end always consists of the bases CCA (cytosine, cytosine, alanine). The anticodon loop always possesses seven nucleotide residues. Attaching amino acids to the tRNA requires energy via a reaction catalyzed by specific enzymes called aminoacyl-tRNA synthetases, often called amino acyl-tRNA ligases. The cleavage of ATP generates AMP plus PPi. To attach the amino acid to its tRNA also requires a specific aminoacyl-tRNA synthetase, and, consequently, all cells must contain at least one aminoacyl-tRNA synthetase for each of the 20 protein amino acids. It selectively recognizes both a specific amino acid and a specific tRNA to which that amino acid should be attached. Aminoacyl-tRNA synthetase molecules are also large, very complex structures as are most all of the components of the process described here. A tRNA molecule to which an amino acid is attached is charged (chemically bonded) or aminoacylated. When its amino acid is released, it is uncharged.
The aminoacyl-tRNA synthetases rarely make a mistake, but when one occurs the system often recognizes the mistake and catalyzes the hydraulic removal of the improperly placed amino acid, a process called proofreading. Amino acids are initially attached to the tRNAs by an ester link to either the two- or three-prime position of the ribose residue within the three-prime terminal nucleotide residue.
Next, a peptide bond forms between the two amino acids held by the two tRNAs partly due to the reaction of the high-energy bond between the activated amino acid and the tRNA formed due to ATP. The larger ribosomal subunit also contains the enzymes required for the peptide bond formation. Each added amino acid is connected to the chain by dehydration synthesis. Then the bond between the first tRNA and its amino acid is cleaved, and the second tRNA then moves into the ribosome site previously occupied by the first tRNA. Next, the ribosome moves down exactly three nucleotides, a step requiring a protein called elongation factor-G (EF-G).
The tRNA structure also uses several slightly modified bases such as inosine. The bases are modified after the tRNA strand is produced by special enzymes, including methylases, deaminases, thiolases, pseudourydylating enzymes and transglycosylases. The correct amino acid bonds to its mate tRNA with the aid of enzymes called tRNA synthetases using energy from ATP.
Each tRNA type requires a specific tRNA synthetase and at least twenty different enzyme tRNA synthetases to exist. They function by, first, an ATP docking in a slot on the enzyme, then an amino acid docks nearby and is “charged” by the ATP losing two of its phosphates. The energized amino acid can now bond to the correct tRNA so that the proper place at the 3’ end of tRNA can bind. At least one tRNA molecule exists for each of the 20 amino acids.
Concurrently, the bond between the tRNA and its amino acid is then broken by hydrolysis. Finally, the empty tRNA floats away to be recharged so it can carry yet another amino acid to be bonded to the growing peptide chain. The mRNA is usually read by more than one ribosome (called a polysome or polyribosome for free ribosomes) simultaneously for efficiency. This allows more proteins to be made from a single mRNA before it is degraded. Protein synthesis often progresses at a rate of about 15 amino acids per second. This process occurs until one of the three stop codons (UAA, UAG, UGA) is reached, and the two parts of the ribosome then separate, dropping off the messenger rRNA. Translation stops when the stop codes are reached because no tRNA exists for these three codes to which an anticodon can bond. A protein called a releasing factor competes for a mRNA base pair but does not bind if a tRNA exists for a codon triplicate.
The releasing factor results in the hydrolysis of the ester bond between tRNA and the polypeptide chain, releasing the completed polypeptide. It then often undergoes post-translational modification, such as the addition of sugars called glycosylation or hydroxylation, the adding of hydroxyl groups to form hydroxyproline and hydroxylysine, respectively. Lastly, the protein chains undergo folding as discussed above. The mRNA itself is eventually broken down by a ribonuclease and its parts, mostly nucleotides, are recycled into new RNA strands. The cell uses this system as one way of achieving tight control of protein synthesis. Gross adds that
Many proteins rely on molecular chaperones to avoid misfolding and aggregation. As the process of RNA folding and ribosome assembly is even more complex and error-prone, it is reasonable to expect that it receives similar help in the [ribosome] in the cell.
Thus new research Gross describes only makes the process described above even more complicated.
Evolutionists’ Pathetic Attempt to Explain the System Just Described
This is only a brief review of some of the major steps required to produce protein from the DNA instructions. The system will not work, and life will not survive until all of the parts or their counterparts described above, plus many more, exist, and are constructed within very narrow tolerances. Evolutionists have no idea how this complex system could have evolved as a functional unit. One recent effort will now be reviewed. The evolution story is:
One day, more than three billion years ago, an RNA catalyst arose that could link amino acids together to form a peptide bond. This catalytic spark set the stage for the division of labor between nucleic acids and proteins that defines life today. Over evolutionary timescales, it also led to the most complex molecular apparatus found in cells — the ribosome.
The essential conclusion of the new research is, because ribosomes are manufactured in sections, the sections evolved independently first and serve an enzyme function and, only later, came together to form the modern ribosome. Thus the ribosome parts performed only catalytic functions until they came together to function as a ribosome. The problem is, until the ribosome sections are assembled, the cell could not live. The ribosomes would serve no function without all of the other necessary parts of the system, including DNA, RNA, tRNA, mRNA and the thousands of other parts required. Furthermore, this new discovery Gross describes creates more problems for evolution, namely each domain of the ribosome must fold and assemble
sequentially as the RNA is produced by the RNA polymerase. This gradual build-up of structure can help with the problems to an extent. However, some key interactions in the RNA folding are between nucleotides far away from each other in the sequence, so there still is a risk of some misfolding while a given nucleotide is waiting for its intended binding partner to show up.
Consequently, until its binding partner shows up and binds with the existing part to form a functional ribosome, another system has to be added to the cell to ensure the required parts are concurrently manufactured, sent to the correct location for assembly, directed in proper alignment for assembly until the bonding occurs, requiring a new set of specific enzymes to create the bond. This problem is confusing to describe, but in real life could not occur. All of the parts must exist and function as a unit for life to exist, and the partial assembly that comes together to produce a functional ribosome idea fails.
New research in biochemistry and cell biology consistently creates new problems for evolution. In addition to the natural-selection hurdles noted above, research groups led by André Schneider at the University of Bern and Nenad Ban of the ETH Zurich
have studied the assembly of mitochondrial ribosomes in the parasite Trypanosoma brucei, which causes sleeping sickness in humans [Science (2019) 365:1144–1149]. Its ribosome is remarkably different from the bacterial version in that it contains many more proteins and a reduced length of RNA strands.
Not to be outdone, chemistry researcher and science journalist Michael L. Gross noted this research has added insight to
the common root of conventional phylogenetic trees, the last universal cellular ancestor (LUCA). Phylogeny tells us that LUCA already possessed a complex translation apparatus similar to the one that is still around in bacteria. On the assumption that this ancestral set of molecules evolved from duplications of a smaller set, research into tRNA synthetases, for instance, has led to deeper roots beyond LUCA, with just two different synthetases presumed to be the ancestors of today’s diversity.
In other words, the LUCA looks very much like that existing in modern bacteria, causing problems to the common molecules-to-man theory. A major plank in the creation worldview firmly supported by science is life must have been created fully-functionally complete and living in all its required complexity, ex nihilo from nothing.
 Kornberg, Arthur. 1989. For the Love of Enzymes. Cambridge, MA: Harvard University Press, p. 316.
 Gross, Michael. 2020. “How to Build Complexity.” Current Biology 30(10):R454-456, May 18, p. R454.
 Jorde, Lynn B. John C. Carey, and Raymond L. White. 1997. Medical Genetics. St. Louis, MO: Mosby, p. 39.
 Levine, Joseph S. and David Suzuki. 1993. The Secret of Life: Redesigning the Living World. Boston, MA: Wgbh Publishing..
 Frank-Kamenetskii, Maxim D. 1993. Unraveling DNA. New York, NY: VCH (Verlag Chemie), p. 20.
 Behe, Michael J. 1996 Darwin’s Black Box: The Biochemical Challenge to Evolution. New York, NY: The Free Press, p. 273.
 Zubay, Geoffrey L. William W. Parson, and Dennis E. Vance. 1995. Principles of Biochemistry. Dubuque, IA.: Wm. C. Brown Publishers.
 Zubay, Geoffrey L., et al.,1995
 Mader, Sylvia S. 1993. Biology. Dubuque, IA: Wm. C. Brown Publishers, p. 256.
 Bergman, Jerry. 2005. “The Mutational Repair System: A Major Problem for Macroevolution.” CRSQ 41(4):265-273, March.
 Zubay, Geoffrey L., et al.,1995.
 Hoagland, Mahlon B. and Bert Dodson. 1995. The Way Life Works. New York, NY: Random House, pp. 114-115.
 Singleton, Paul and Diana Sainsbury. 1994. Dictionary of Microbiology and Molecular Biology, 2nd ed. New York, NY: John Wiley & Sons, p. 712.
 Gross, 2020, p. R455. Emphasis added.
/>Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,500 college libraries in 27 countries. So far over 80,000 copies of the 40 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.
Historically, the ribosome has been viewed as a complex ribozyme with constitutive rather than intrinsic regulatory capacity in mRNA translation. However, emerging studies reveal that ribosome activity may be highly regulated. Heterogeneity in ribosome composition resulting from differential expression and post-translational modifications of ribosomal proteins, ribosomal RNA (rRNA) diversity and the activity of ribosome-associated factors may generate 'specialized ribosomes' that have a substantial impact on how the genomic template is translated into functional proteins. Moreover, constitutive components of the ribosome may also exert more specialized activities by virtue of their interactions with specific mRNA regulatory elements such as internal ribosome entry sites (IRESs) or upstream open reading frames (uORFs). Here we discuss the hypothesis that intrinsic regulation by the ribosome acts to selectively translate subsets of mRNAs harbouring unique cis-regulatory elements, thereby introducing an additional level of regulation in gene expression and the life of an organism.
A ribosome functions as a micro-machine for making proteins. Ribosomes are composed of special proteins and nucleic acids. The TRANSLATION of information and the Linking of AMINO ACIDS are at the heart of the protein production process.A ribosome, formed from two subunits locking together, functions to: (1) Translate encoded information from the cell nucleus provided by messenger ribonucleic acid (mRNA), (2) Link together amino acids selected and collected from the cytoplasm by transfer ribonucleic acid (tRNA). (The order in which the amino acids are linked together is determined by the mRNA) and, (3) Export the polypeptide produced to the cytoplasm where it will form a functional protein.
Ribosomes are found ‘free’ in the cytoplasm or bound to the endoplasmic reticulum (ER) to form rough ER. In a mammalian cell there can be as many as 10 million ribosomes. Several ribosomes can be attached to the same mRNA strand, this structure is called a polysome. Ribosomes have only a temporary existence. When they have synthesised a polypeptide the two sub-units separate and are either re-used or broken up.
Ribosomes can join up amino acids at a rate of 200 per minute. Small proteins can therefore be made fairly quickly but two to three hours are needed for larger proteins such as the massive 30,000 amino acid muscle protein titin.
Ribosomes in prokaryotes use a slightly different process to produce proteins than do ribosomes in eukaryotes. Fortunately this difference presents a window of molecular opportunity for attack by antibiotic drugs such as streptomycin. Unfortunately some bacterial toxins and the polio virus also use it to enable them to attack the translation mechanism.
For an overview diagram of protein production click here.
(The diagram will open in a separate window)
This is an electron microscope image showing part of the rough endoplasmic reticulum in a plant root cell from maize. The dark spots are ribosomes.
(courtesy of Chris Hawes, The Research School of Biology & Molecular Sciences, Oxford Brookes University, Oxford, UK)
A LONGER LOOK at Ribosomes:
Ribosomes are macro-molecular production units. They are composed of ribosomal proteins (riboproteins) and ribonucleic acids (ribonucleoproteins). The word ribosome is made from taking ‘ribo’ from ribonucleic acid and adding it to ‘soma’, the Latin word for body. Ribosomes can be bound by a membrane(s) but they are not membranous.
Ribosome: a micro-machine for manufacturing proteins
A ribosome is basically a very complicated but elegant micro-‘machine’ for producing proteins. Each complete ribosome is constructed from two sub-units. A eukaryotic ribosome is composed of nucleic acids and about 80 proteins and has a molecular mass of about 4,200,000 Da. About two-thirds of this mass is composed of ribosomal RNA and one third of about 50+ different ribosomal proteins.
Ribosomes are found in prokaryotic and eukaryotic cells in mitochondria, chloroplasts and bacteria. Those found in prokaryotes are generally smaller than those in eukaryotes. Ribosomes in mitochondria and chloroplasts are similar in size to those in bacteria. There are about 10 billion protein molecules in a mammalian cell and ribosomes produce most of them. A rapidly growing mammalian cell can contain about 10 million ribosomes. [A single cell of E. Coli contains about 20,000 ribosomes and this accounts for about 25% of the total cell mass].
The proteins and nucleic acids that form the ribosome sub-units are made in the nucleolus and exported through nuclear pores into the cytoplasm. The two sub-units are unequal in size and exist in this state until required for use. The larger sub-unit is about twice as large as the smaller one.
The larger sub-unit has mainly a catalytic function the smaller sub-unit mainly a decoding one. In the large sub-unit ribosomal RNA performs the function of an enzyme and is termed a ribozyme. The smaller unit links up with mRNA and then locks-on to a larger sub-unit. Once formed ribosomes are not static units. When production of a specific protein has finished the two sub-units separate and are then usually broken down. Ribosomes have only a temporary existence.
Sometimes ribosome sub-units admit mRNA as soon as the mRNA emerges from the nucleus. When many ribosomes do this the structure is called a polysome. Ribosomes can function in a ‘free’ state in the cytoplasm but they can also ‘settle’ on the endoplasmic reticulum to form ‘rough endoplasmic reticulum’. Where there is rough endoplasmic reticulum the association between ribosome and endoplasmic reticulum (ER) facilitates the further processing and checking of newly made proteins by the ER.
The Protein Factory: site and services.
All factories need services such as gas, water, drainage and communications. For these to be provided there must a location or site.
Protein production also needs service requirements. A site requiring the provision of services is produced in a small ribosome sub-unit when a strand of mRNA enters through one selective cleft, and a strand of initiator tRNA through another. This action triggers the small sub-unit to lock-on to a ribosome large sub-unit to form a complete and active ribosome. The amazing process of protein production can now begin.
For translation and protein synthesis to take place many initiator and release chemicals are involved, and many reactions using enzymes take place. There are however general requirements and these have to be satisfied. The list below shows the main requirements and how they are provided:
- Requirement: A safe (contamination free) and suitable facility for the protein production process to take place.
- Provision: this facility is provided by the two ribosomal sub-units. When the two sub-units lock together to form the complete ribosome, molecules entering and exiting can only do so through selective clefts or tunnels in the molecular structure.
- Requirement: A supply of information in a form that the ribosome can translate with a high degree of accuracy. The translation must be accurate in order that the correct proteins are produced.
- Provision: Information is supplied by the nucleus and delivered to the ribosome in the form of a strand of mRNA. When mRNA is formed in the nucleus introns (non-coding sections) are cut out, and exons (coding sections) are joined together by a process called splicing.
- Requirement: A supply of amino acids from which the ribosomal mechanism can obtain the specific amino acids needed.
- Provision: Amino acids, mainly supplied from food, are normally freely available in the cytoplasm.
- Requirement: A system that can select and lock-on to an amino acid in the cytoplasm and deliver it to the translation and synthesis site in the ribosome.
- Provision: Short strands of transfer ribonucleic acid (tRNA) made in the nucleus and available in the cytoplasm act as ‘adaptor tools’. When a strand of tRNA has locked on to an amino acid the tRNA is said to be ‘charged’. tRNA diffuses into the smaller ribosome sub-unit and each short tRNA strand will deliver ONE amino acid.
- Requirement: A means of releasing into the cytoplasm: (a) a newly formed polypeptide, (b) mRNA that has been used in the translating process, and (c) tRNA that has delivered the amino acid it was carrying and is now ‘uncharged’.
- Provision: (a) when a newly formed peptide chain is produced deep inside the ribosome large sub-unit, it is directed out to the cytoplasm along a tunnel or cleft. (b) ‘Used’ mRNA leaves the smaller ribosome sub-unit through a tunnel on the side opposite to its point of entry. Movement through the ribosome is brought about by a one-way only, intermittent movement of the ribosome along, and in the direction of, the incoming mRNA strand. (c) tRNA in the ‘uncharged’ state leaves via a tunnel in the molecular architecture of the ribosome large sub-unit.
The Protein Factory: What happens on the inside?
– A look at the protein production line that can join up amino acids at a rate of 200 per minute!
Now we have considered the requirements and provisions needed for the protein production machine to operate, we can look at the inner workings.
As mentioned earlier many detailed biochemical reactions take place in the ribosome and only a brief outline is given here to illustrate the concept.
(Please also see ‘schematic of ribosome’ at end of section)
In the ribosome there are THREE STAGES and THREE operational SITES involved in the protein production line.
The three STAGES are (1) Initiation, (2) Elongation and (3) Termination.
The three operational or binding SITES are A, P and E reading from the mRNA entry site (conventionally the right hand side).
Sites A and P span both the ribosome sub-units with a larger part residing in the ribosome large sub-unit, and a smaller part in the smaller sub-unit. Site E, the exit site, resides in the large ribosome sub-unit.
Table of binding sites, positions and functions in a ribosome
(please also see schematic of ribosome at end of section)
mRNA strand entry site
Admission of codon of mRNA & ‘charged’ strand of tRNA. Checking and decoding and start of ‘handing over’ one amino acid molecule
Peptide synthesis, consolidation, elongation and transfer of peptide chain to site A
Preparation of ‘uncharged’ tRNA for exit
The Three stages:
- Initiation. During this stage a small ribosome sub-unit links onto the ‘start end’ of an mRNA strand. ‘Initiator tRNA’ also enters the small sub-unit. This complex then joins onto a ribosome large sub-unit. At the beginning of the mRNA strand there is a ‘start translating’ message and a strand of tRNA ‘charged’ with one specific amino acid, enters site A of the ribosome. Production of a polypeptide has now been initiated.For the tRNA not to be rejected the three letter code group it carries (called an anti-codon) must match up with the three letter code group (called a codon) on the strand of mRNA already in the ribosome. This is a very important part of the translation process and it is surprising how few ‘errors of translation’ occur. [In general the particular amino acid it carries is determined by the three letter anticodon it bears, e.g. if the three letter code is CAG (Cytosine, Adenine, Guanine) then it will select and transport the amino acid Glutamine (Gln)].
- Elongation.This term covers the period between initiation and termination and it is during this time that the main part of the designated protein is made. The process consists of a series of cycles, the total number of which is determined by the mRNA. One of the main events during elongation is translocation. This is when the ribosome moves along the mRNA by one codon notch and a new cycle starts.During the ‘start-up’ process the ‘initiation tRNA’ will have moved to site P (see schematic of ribosome at end of section) and the ribosome will have admitted into site A, a new tRNA ‘charged’ with one amino acid.The ‘charged’ tRNA resides in site A until it has been checked and accepted (or rejected) and until the growing peptide chain attached to the tRNA in site P, has been transferred across by enzymes, to the ‘charged’ tRNA in site A. Here one new amino acid is donated by the tRNA and added to the peptide chain. By this process the peptide chain is increased in length by increments of one amino acid. [The peptide bond formation between the growing peptide chain and the newly admitted amino acid is assisted by peptidyl transferase and takes place in the large ribosome sub-unit. The reaction occurs between tRNA that carries the nascent peptide chain, peptidyl-tRNA and the tRNA that carries the incoming amino acid, the aminoacyl-tRNA]. When this has taken place the tRNA in site P, having transferred its peptide chain, and now without any attachments, is moved to site E the exit site.Next, the tRNA in site A, complete with a peptide chain increased in length by one amino acid, moves to site P. In site P riboproteins act to consolidate the bonding of the peptide chain to the newly added amino acid. If the peptide chain is long the oldest part will be moved out into the cytoplasm to be followed by the rest of the chain as it is produced.The next cycle
With site A now empty translocation takes place. The ribosome moves on by a distance of one (three letter) codon notch along the mRNA to bring a new codon into the processing area. tRNA ‘charged’ with an attached amino acid now enters site A, and provided a satisfactory match of the mRNA codon and tRNA anti-codon is made, the cycle starts again. This process continues until a termination stage is reached.
- Termination. When the ribosome reaches the end of the mRNA strand, a terminal or ‘end of protein code’ message is flagged up. This registers the end of production for the particular protein coded for by this strand of mRNA. ‘Release factor’ chemicals prevent any more amino acid additions, and the new protein (polypeptide) is completely moved out into the cytoplasm through a cleft in the large sub-unit. The two ribosome sub-units disengage, separate and are re-used or broken down.
- Nearly all the proteins required by cells are synthesised by ribosomes. Ribosomes are found ‘free’ in the cell cytoplasm and also attached to rough endoplasmic reticulum.
- Ribosomes receive information from the cell nucleus and construction materials from the cytoplasm.
- Ribosomes translate information encoded in messenger ribonucleic acid (mRNA).
- They link together specific amino acids to form polypeptides and they export these to the cytoplasm.
- A mammalian cell may contain as many as 10 million ribosomes, but each ribosome has only a temporary existence.
- Ribosomes can link up amino acids at a rate of 200 per minute.
- Ribosomes are formed from the locking of a small sub-unit on to a large sub-unit. The sub-units are normally available in the cytoplasm, the larger one being about twice the size of the smaller one.
- Each ribosome is a complex of ribonucleoproteins with two-thirds of its mass is composed of ribosomal RNA and about one-third ribosomal protein.
- Protein production takes place in three stages: (1) initiation, (2) elongation, and (3) termination.
- During peptide production the ribosome moves along the mRNA in an intermittent process called translocation.
- Antibiotic drugs such as streptomycin can be used to attack the translation mechanism in prokaryotes. This is very useful. Unfortunately some bacterial toxins and viruses can also do this.
- After they leave the ribosome most proteins are folded or modified in some way. This is called ‘post translational modification’.
An overview diagram of protein production, including a note about protein modification.
I have argued that the RNA world hypothesis, while certainly imperfect, is the best model we currently have for the early evolution of life. While the hypothesis does not exclude a number of possibilities for what – if anything – preceded RNA, unfortunately the evolution of coded protein synthesis has drawn a veil over the previous history of proteins. The situation is different in the case of non-coding RNAs such as ribosomal RNA and tRNA, as these were able to replicate prior to the evolution of ribosomal protein synthesis.
As we have noted previously , the proposal that the RNA world evolved in acidic conditions [5, 6] offers a plausible solution to Charles Kurland's criticism  that the RNA world hypothesis makes no reference to a possible energy source. As de Duve  has noted, "the widespread use of proton-motive force for energy transduction throughout the living world today is explained as a legacy of a highly acidic prebiotic environment and may be viewed as a clue to the existence of such an environment" . Although Russell, Martin and others [23–26] have argued that proton and thermal gradients between the outflow from hot alkaline (pH 9-11) under-sea hydrothermal vents and the surrounding cooler more acidic ocean may have constituted the first sources of energy at the origin of life, the lack of RNA stability at alkaline pH ( and references within) would appear to make such vents an unlikely location for RNA world evolution.
Although possible, it seems unlikely that the A-C base pair 'mismatches' found in the tRNA genes of Ferroplasma acidarmanus and Picrophilus torridus (two species of archaebacteria with a reportedly acidic internal pH)  are corrected by C to U RNA editing that occurs, for example, with some - but not other - plant chloroplast tRNAs [88, 89]. Such editing of secondary structure A-C base pair mismatches has so far not been found to occur in archaebacteria however, in a single archaeal species (Methanopyrus kandleri) a tertiary structure A-C base pair found in 30 of its 34 tRNAs undergoes C to U editing catalyzed by a cytidine deaminase CDAT8 . M. kandleri is a unique organism that contains many 'orphan' proteins. CDAT8, which contains a cytidine deaminase domain and putative RNA-binding domain, has no homologues in other arachaeal species, including F. acidarmanus and P. torridus (L Randau, pers. commun. ). Definitive proof, however, that the A-C base pairs in these two species are not modified would of course require e.g. cDNA sequencing of the tRNAs.
Ribosomes Optimized for Speed, Flexibility
The DNA translation machines in the cell show unexpected complexity, forcing molecular biologists to revise what they thought they knew about ribosomes. In particular, they appear optimized for speed of self-duplication and modularized for flexibility.
Last September, we evaluated a fascinating paper about ribosomes that showed how this molecular machine that translates DNA “requires the orchestrated function of hundreds of proteins” — and that’s just to get to the “pre-ribosome” stage! Ribosomes are marvels of organization and function. Since then, more discoveries have shown additional design features of ribosomes.
A cell doesn’t have all day to build and operate these machines. In July, a paper in Science Advances revised the half-life of RNAs significantly downward. Instead of 5-20 minutes to float around and get translated, most messenger RNAs (mRNAs) last only about 2 minutes before being degraded by complex recycling pathways (see this from the University of Basel). The production rate and decay rate are important factors in gene regulation. So if you think of “orchestrated function” again, the sheet music won’t do any good if the stage isn’t already set up and the players aren’t in their seats.
The ribosome is composed of large RNAs and proteins. The paper doesn’t state the half-life of the ribosomal RNAs, which make up the bulk of the ribosome, but it’s safe to assume the lifetime of each RNA is finite — probably a matter of minutes. An extra reason for assuming this is the rapid doubling of ribosomes during cell division. Before the cell can divide, all the proteins needed by the two daughter cells must be translated. This requirement effectively doubles the work for these machines.
How does the cell prepare for this increased workload? Rather than speed up translation, the ribosomes first duplicate themselves, effectively doubling the production capacity. This means that they have to prepare and assemble all their own RNAs and proteins first. Without efficient ways to accomplish this prerequisite, cell division could be seriously delayed.
An interesting model, published in Nature by Johan Paulsson’s team at Harvard, suggests that “Ribosomes are optimized for autocatalytic production.” They knew that ribosomes are already optimized in three ways. Now, they add a fourth:
Many fine-scale features of ribosomes have been explained in terms of function, revealing a molecular machine that is optimized for error-correction, speed and control. Here we demonstrate mathematically that many less well understood, larger-scale features of ribosomes — such as why a few ribosomal RNA molecules dominate the mass and why the ribosomal protein content is divided into 55–80 small, similarly sized segments — speed up their autocatalytic production. [Emphasis added.]
The authors, as evolutionists, will assume that Darwinian processes achieved this optimization. In their own words, however, we sense their astonishment at what these machines accomplish.
Ribosomes translate sequences of nucleic acids into sequences of amino acids. Their features are therefore typically explained in terms of how they affect translation. However, in recent years it has also become clear that ribosomes are exceptional as products of the ribosomal machinery. Not only do ribosomal proteins (r-proteins) make up a large fraction of the total protein content in many cells, but the autocatalytic nature of ribosome production introduces additional constraints. Specifically, the ribosome doubling time places a hard bound on the cell doubling time, because for every additional ribosome to share the translation burden there is also one more to make. Even for the smallest and fastest ribosomes, it takes at least 6 min, and typically much longer, for one ribosome to make a new set of r-proteins (Supplementary Information) and this estimate does not account for the substantial time that is invested in the synthesis of ternary complexes. This bound seems to explain the observed limits on bacterial growth, because ribosomes must also spend much of their time making other proteins, and shows that ribosomes are under very strong selective pressure to minimize the time they spend reproducing.
Whether “selective pressure” is the mother of invention is debatable to those of us who are Darwin skeptics, but the authors point out something important. The “orchestrated function of hundreds of proteins” has time limits. The conductor is pounding his foot and tapping his baton on the podium, rushing the orchestra to get in place. Imagine how much harder if each player, instrument, chair, and music stand has to make a copy of itself first for a show across town!
Based on observed facts about ribosomal RNAs and proteins, and how quickly they duplicate, the team created a mathematical model based on the assumption that “selective pressure” forces cells to optimize their ribosomes’ doubling time. Although the model worked for fast-reproducing bacteria, they presume the same time pressure constrains eukaryotic cells:
Similar principles might also apply to some eukaryotes, because the ribosomes of eukaryotes are larger and slower. In fact, even organisms in which cell doubling times are not limited by ribosome doubling times would benefit from faster ribosome production, allowing ribosomes to spend more of their time producing the rest of the proteome. This efficiency constraint was recently shown to have broad physiological consequences for cells, and here we demonstrate mathematically that it might also explain many broader features of the ribosome (Fig. 1).
In the figure, they show that ribosomes are dominated by a few large RNAs and lots of small proteins, about 55 to 80 of them of similar size. The reason for this arrangement has long puzzled molecular biologists. According to the new model, ribosomes can reproduce their parts quicker when the proteins are relatively short, and there are lots of them. The existing ribosomes can crank out smaller building blocks faster, and the construction workers can assemble them faster, than if they had to wait for long, complex pieces to arrive.
It’s not necessary to get into the weeds to see the elegance of the solution. Ribosomes assemble faster with more, smaller proteins, reducing the time to duplicate themselves, so that they can get on with their main job of translating all the other proteins the cell needs before dividing. The faster you double the translating machinery, the faster you can double everything else in the cell.
The model also needs to explain why ribosomes include a few large RNAs. Evolutionists have typically invoked the “RNA World” story to suggest that ribosomal RNAs represent transitional forms or vestiges from the origin of life before cells happened upon ways to make proteins. Paulsson’s model suggests a different reason — a functional reason. RNAs only need to be transcribed, not translated. RNA enzymatic activity is not as efficient as protein, but RNA is quicker to make. The cell, therefore, is better off using it when time is of the essence.
The above analysis suggests a great efficiency advantage of using rRNA [ribosomal RNA] over protein, whenever chemically possible, and so could explain why ribosomes defy the general rule that enzymes are made mostly of protein (Fig. 1). This finding does not mean that the role of rRNA is merely to ensure appropriate overall dimensions of the ribosome however, it does provide a fundamental reason for why proteins must be used sparingly in the ribosome, for example, to increase accuracy or speed up translation, whereas rRNA should be used wherever possible without compromising function. If even one-quarter of the rRNA mass were replaced with r-protein without increasing translation rates, many bacteria would not be able double as quickly as they do (Fig. 4b).
Do you see optimization (a form of intelligent design) at work? The authors go into more detail about why rRNAs must be large. Their model shows that small rRNAs, unlike the small ribosomal proteins, would actually slow down duplication. Suffice it to say that the observed ratio of rRNA to ribosomal protein increases the efficiency by two orders of magnitude. Here’s a pithy analogy from a layman’s summary of the paper at Science Daily:
“An analogy for our findings would be to think of ribosomes not as a group of carpenters who merely build a lot of houses, but as carpenters who also build other carpenters,” Paulsson said. “There is then an incentive to divide the job into many small pieces that can be done in parallel to more quickly assemble another complete carpenter to help in the process.”
One other mystery about ribosomes might be solved by looking at it as an optimization problem: why do ribosomes vary? Mitochondrial ribosomes differ from those in the cytosol. Eukaryotic ribosomes differ from those of bacteria. If they perform the same function, why aren’t they all the same? Here’s a paper in PLOS ONE from last November that opens a window on a possible reason: ribosome structure is modularized. In “The Modular Adaptive Ribosome,” a team from India says this:
The ribosome is an ancient machine, performing the same function across organisms. Although functionally unitary, recent experiments suggest specialized roles for some ribosomal proteins. Our central thesis is that ribosomal proteins function in a modular fashion to decode genetic information in a context dependent manner.
Interested readers can delve further into this open-access paper to see why ribosomes vary in different cell types or different environments. “A clear example is nervous tissue that uses a ribosomal protein module distinct from the rest of the tissues in both mice and humans,” they say. “Our results suggest a novel stratification of ribosomal proteins that could have played a role in adaptation, presumably to optimize translation for adaptation to diverse ecological niches and tissue microenvironments.”
When it comes to ribosomes, it appears to be a case of optimization all the way down.
Let’s give the last word to the Science Daily article.
Rather than being mere relics of an evolutionary past, the unusual features of ribosomes thus seem to reflect an additional layer of functional optimization acting on collective properties of its parts, the team writes.
“While this study is basic science, we are addressing something that is shared by all life,” Paulsson said. “It is important that we understand where the constraints on structure and function come from, because like much of basic science, it is unpredictable what the consequences of new knowledge can unlock in the future.”
Notice how that downplays evolution’s role, in spite of the authors’ Darwinian views. It also, even if not intending to do so, supports a design pespective, while showing how such a focus leads to productive science.
Top 25 Biology Discoveries
Here are the top 25 biology discoveries of all time.
First compound microscope.
The father and son team from German town Middleburg have placed two spectacle lenses into a tube, one above the other and found out that such an instrument helps see microscopic objects.
- Some of their microscopes even had three lenses and had considerable magnification, also if the images were unclear.
- Their invention had a significant impact on the development of science – without the microscope, it would have been impossible to study cells, small animals, or bacteria.
Blood circulation in animals.
William Harvey was a British doctor. He has performed multiple dissections on dogs.
- He also had demonstrated his experiments before the other surgeons. Harvey has shown that the blood circulates in two loops: the pulmonary circulation and systemic circulation.
- He has also discovered valves in veins and determined that blood can only move in specific directions in the body.
- He has published his findings in a book called “Anatomical Study of the Motion of the Heart and of the Blood in Animals“.
- Understanding how our blood vessels work was crucial for medicine and physiology. It has impacted treatments of the time and raised the interest in anatomy.
The first description of cells.
Robert Hooke was an accomplished inventor and scientist, a member of the Royal Society of London.
- He has improved the microscope made by Janssens and was able to be the first person in history to describe cells in plant tissue.
- He has also depicted many other vital structures of plants, insects, and other animals.
- Hooke’s discoveries have started a trend in using microscopes for life studies, which have eventually led to multiple crucial discoveries.
- He has also become an example of proper scientific inquiry and high-quality scientific drawing.
- It would not have been possible to formulate the cell theory without Hooke’s discovery either.
Discovery of Microorganisms.
Leeuwenhoek has built his own small microscope and with its help has studied life histories of insects and microscopic organisms, such as protozoa and bacteria.
- He was also the first to show that microscopic organisms, which he has called animalcules, were present in water, on various surfaces, as well as foodstuffs.
- His discoveries were the start of microbiology and entomology. Without his work, people would not know that microorganisms cause illnesses and contamination.
Classification of life.
|Karl Linnaeus||1758||A first universal classification system of living beings was proposed.|
Karl Linnaeus, a Swedish scientist, has proposed a universal system of classification of living beings.
- The new system was hierarchical, Latin-based, and allowed easy communication between scientists.
- Each species was given a unique binomial name and belonged to a particular genus, family, order, class, and kingdom.
- Linnaeus system has been modified several times since then, but the initial idea still remains the same.
- The existence of the classification system has made the study of life significantly easier and also allowed to study evolutionary relationships between organisms in later centuries.
Bacteria are not a product of a spontaneous generation.
The experiment carried out by an Italian abbot and professor, Lazarro Spallanzani, has proven that microbes are not created through non-living “life force”, but can only come from other microorganisms.
- This experiment has helped people admit that all animals, without exception descend from other animals of the same type, overthrowing the previously popular “spontaneous generation” theory.
- Spallanzani’s experiment has contributed to our understanding of the role of microorganisms and where they come from.
- It was also the basis for pasteurization method, later developed by Pasteur.
|Theodor Schwann, Matthias Schleiden, Rudolf Virchow||1838 and 1858||The establishment of cell theory.|
Theodor Schleiden, an animal specialist, and Matthias Schleiden, a botanist have come to the common conclusion: all living beings consist of units with similar shape and structure – cells.
They have formulated the cell theory:
- All living beings are made of cells.
- Each cell is both a functional unit and a building block.
Later in 1858, an outstanding German anatomist has postulated a third important rule to the cell theory: all cells descend from other cells. The formulation of the cell theory was the start of cell biology as we know it. Without it, we would not understand many processes and certainly would not be able to fight such diseases as cancer.
Louis Pasteur, a French microbiologist, and chemist are considered the father of modern microbiology.
- His work was extremely extensive. His most notable achievements are proving beyond doubt that bacteria caused illnesses and the invention of pasteurization based on earlier Spallanzani’s experiment.
- We rely on pasteurization up to this day to preserve our food. Without vaccines and culture methods developed by Pasteur, we would not have been able to fight diseases of cattle and humans.
Theory of Evolution.
The British scientists Charles Darwin and Alfred Wallace have independently formulated a theory that explained the origins of life on Earth and mechanisms of evolution of species.
- Evolutionary theory has expanded dramatically since Darwin’s time, but the existence of natural selection is virtually undisputed up to this day.
- Darwin’s work has contributed significantly to our understanding of life on Earth and the processes that are still taking place today.
The laws of heredity.
Gregor Mendel, an Austrian monk, and a mathematician have postulated the mechanisms of transferring inherited traits from parents to offspring.
- He has used pea plants for his experiments and has discovered the existence of dominant and recessive alleles.
- Mendelian genetics is only one aspect of the complex mechanism of inheritance, but it still plays a massive role in breeding programs in agriculture and the understanding of human disorders.
- Mendel also introduced statistics as a method of evaluating results and drawing conclusions, which is now widely used in all sciences.
Ilya (Elie) Mechnikov has discovered the existence of specialized cells in animals (both vertebrate and invertebrate) that were responsible for eliminating pathogens and dead cells.
- ‘Mechnikovs discovery has started immunology – the science devoted to the study of defense mechanisms against pathogens inside the body.
- Immunology helps significantly in our fight against pathogens and also in vaccine development.
Chromosomes and their role in fertilization.
Edouard van Beneden, a Belgian embryologist and cytologist, has published several papers since 1883, describing chromosomes in the Ascaria worms eggs, as well the processes of fertilization and mitosis.
Without his discoveries, the next breakthroughs in understanding heredity in general and chromosome disorders, in particular, would have been impossible.
Tobacco mosaic virus.
The Russian scientist Dmitriy Ivanovsky was studying tobacco plants that were affected by the illness called tobacco mosaic.
- He has proven that the illness was caused by an agent that was far smaller than regular bacteria.
- The actual term, “virus“, was coined later by Martinus Beijerinck in 1898.
- Due to the elegant experiment carried out by Ivanovsky, the scientific community has learned about viruses even though they could not really see them until the invention of the electron microscope.
Inheritance of alkaptonuria.
Archibald Garrod has studied family charts of patients with a metabolic disorder – alkaptonuria and has figured out that this illness is inherited according to Mendelian laws.
- It was the first description ever of an inheritable disease and the additional proof of the universality of Mendelian laws.
- Due to Garrod’s discovery, specialists could better understand the causes of diseases, such as hemophilia.
While experimenting with two bacterial strains of Staphylococcus pneumoniae, Griffith has discovered that the traits from the dead bacteria can be transferred into living ones.
- This process was called transformation. Griffith’s discovery helped establish the role of DNA in heredity.
- The discovery of transformation and bacterial plasmids has also influenced the development of genetic engineering.
- Due to our knowledge of bacterial transformation, we are also able to understand how antibiotic resistance is spread in bacterial populations.
Alexander Fleming was working at St. Mary’s hospital in London, Great Britain.
- He has accidentally discovered that the presence of certain types of molds in Petri dishes of bacterial cultures kills the bacteria.
- He has also purified the substance responsible for this effect. Though penicillin was discovered in 1928, its production as a drug had not started until the 1940s, when proper antibacterial care was crucial for the wounded soldiers.
- The discovery of penicillin was the start of the antibiotic era, decreasing mortality from illnesses worldwide.
When Hotchkiss was studying a preparation of calf thymus, he has discovered that one of the DNA Nucleotides, cytosine, had an additional methyl group – was methylated.
- Later, it was found that other nucleotides could be methylated, too.
- DNA methylation is one of the most common mechanisms of regulation of gene activity.
- We now know that this type of regulation, called epigenetic regulation is crucial for our development and well-being.
Using the data obtained from X-Ray crystallography and paper models, Linus Pauling has discerned how amino acids fit together to form proteins.
- The first structure he has described was the protein alpha helix. Proteins play major roles in the functioning of cells and complex organisms, and determining their formation was the first step to understanding their activity.
- Pauling’s method has also influenced Watson and Crick and helped establish the DNA structure.
- Pauling’s discovery is now considered the start of molecular biology. Pauling was awarded a Nobel Prize in chemistry in 1954.
Mobile genetic elements.
An American scientist, Barbara McClintock, was studying plants. Her particular area of interest was the mechanism of breaks in the chromosomes of the maize plants.
- She has discovered that there are areas in the chromosomes that can break away and re-insert themselves in other regions.
- This was one of the most astonishing discoveries of the 20th century, upending the scientist’s understanding of how the genome works and how mutations are generated.
- In later decades, it was found that mobile genetic elements (transposons) can be present in all living organisms, from viruses to mammals.
Based on data on the ratio of nucleotides and X-ray images made by another scientist, Rosalind Franklin, Watson and Crick have figured the DNA structure.
- They have shown that DNA is a double spiral with hydrogen bonds between complementary purine and pyrimidine bases.
- The discovery of DNA structure helped figure out the mechanisms of replication, translation, and the DNA code itself.
DNA sequencing method by Frederick Sanger.
Frederick Sanger has developed a method that allows determination of the exact sequence of nucleotides in the genome using DNA polymerase, pre-made primers, and radioactive nucleotides.
His method was significantly more straightforward and quicker than previous ones and helped to substantially speed up the sequencing of DNA in bacteria, viruses, and later humans.
The new kingdom of life.
Carl Woese was sequencing a specific type of nucleic acid – ribonucleic RNA.
- He has discovered unicellular organisms without a nucleus that had a completely different type of ribosomal RNA compared to bacteria and eukaryotes.
- He has shown that those organisms belonged to a completely separate kingdom of life. They were called archaea.
- The modern scientific thought leans towards the idea that eukaryotes actually descended from Archaea through endosymbiosis.
While studying how SV40 virus causes the development of the cancer tumors, Kress and his colleagues discovered a novel protein that was actively produced in the nuclei of cancer cells and was also associated with one of the viral antigens.
- Later research has uncovered that this protein was crucial in two critical processes: cancer development and programmed cell death – apoptosis.
- Among other things, p53 was then found to be involved in the cancerogenic effects of smoking.
Genes controlling autophagy.
Autophagy is a process of self-destruction and recycling in the cell in response to stress.
- Ohsumi has developed a method to study this process in yeast and has managed to find several genes responsible for this process.
- His work has contributed both to science and medicine, as autophagy was found to play a significant role in neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Ohsumi was awarded a Nobel Prize in 2016 for his work.
Cas9/CRISPR system in bacteria.
The team of scientists led by R. Barrangou has discovered that bacteria use special enzymes to cut out pieces of infecting virus that are lately inserted into the bacterial genome.
- This system helps bacteria recognize viruses in time. Later, the scientists realized that those bacterial enzymes can be used for editing genomes of other organisms.
- This discovery was crucial for cancer research, as well as other fields. First, gene editing in humans was also performed using this technique.
The history of biology is full of small and big discoveries that have greatly influenced our lives. These discoveries helped us understand life better and make incredible improvements in medicine.
This biology discoveries list only describes a few that have impacted the development of biology the most.
Biologists probe the machinery of cellular protein factories
Proteins of all sizes and shapes do most of the work in living cells, and the DNA sequences in genes spell out the instructions for making those proteins. The crucial job of reading the genetic instructions and synthesizing the specified proteins is carried out by ribosomes, tiny protein factories humming away inside the cells of all living things.
Harry Noller, the Sinsheimer Professor of Molecular Biology at the University of California, Santa Cruz, has been studying the ribosome for more than 30 years. His main goal is to understand how the ribosome works and how it evolved, but there are also practical reasons to pursue this research. Many of the most effective antibiotics work by targeting bacterial ribosomes, and findings by Noller and others have led to the development of novel antibiotics that hold promise for use against germs that have developed resistance to current drugs. Drug-resistant staph infections, for example, are a serious problem in hospitals.
Noller's laboratory achieved breakthroughs in 1999 and 2001, producing the first high-resolution images of the molecular structure of a complete ribosome. Now, his team has made another major advance with an even higher-resolution image that enables them to construct an atom-by-atom model of the ribosome.
The new picture shows details never seen before and suggests how certain parts of the ribosome move during protein synthesis. A paper describing the new findings will be published in the September 22 issue of the journal Cell and is currently available online.
"We can now explain a lot of the results from biochemical and genetic studies carried out over the past several decades," Noller said. "This structure gives us another frame in the movie that will eventually show us the whole process of the ribosome in action."
The ribosome is a complex molecular machine made up of proteins and RNA molecules. The bacterial ribosomes studied in Noller's lab (obtained from the bacterium Thermus thermophilus) are made up of three different RNA molecules and more than 50 different proteins.
Noller proposed in the early 1970s that the RNA component was responsible for carrying out the ribosome's key functions. At the time it was considered a "crackpot idea," but subsequent findings by Noller and others proved he was right.
"It was a completely heterodox view when we first proposed it, but it is now the accepted paradigm," said Noller, who directs the Center for Molecular Biology of RNA at UCSC. "Our latest results confirm that the ribosomal RNA is really the key to ribosome function. The proteins are also involved, but more peripherally," he said.
To make a new protein, the genetic instructions are first copied from the DNA sequence of the gene into a messenger RNA molecule. The ribosome then reads the genetic code from the messenger RNA and translates it into the structure of a protein.
Proteins are linear molecules that fold into complex three-dimensional shapes to carry out their functions. They are made from amino acid building blocks, and the sequence of amino acids determines the protein's structure. Amino acids are carried to the ribosome by transfer RNA molecules. On the ribosome, the transfer RNAs recognize specific sequences of genetic code on the messenger RNA, and the amino acids are then joined together in the proper order.
The images from Noller's group not only show the complete ribosome, they show it with a messenger RNA and two full-length transfer RNAs bound to it. "We can now see the details of most of the interactions between the ribosome, the messenger RNA, and the transfer RNAs," Noller said.
The results provide a snapshot of the molecular machine in action. By comparing his images with those obtained by other groups that have caught the ribosome or its subunits in different positions, Noller is finding clues to the molecular motions with which the ribosome does its work.
"Our next goal is to trap the ribosome in other functional states to get more frames of the movie," he said.
The authors of the paper, in addition to Noller, are postdoctoral researcher Andrei Korostelev, senior scientist Sergei Trakhanov, and postdoctoral researcher Martin Laurberg. The researchers used a technique called x-ray crystallography, which involves growing crystals of purified ribosomes, shining a focused beam of x-rays through the crystals, and analyzing the resulting diffraction pattern. Trakhanov prepared the crystals and Korostelev and Laurberg performed the crystallography and solved the structure, Noller said.
Pokeweed antiviral protein
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Mimicking living cells: Synthesizing ribosomes
Synthetic biology researchers at Northwestern University, working with partners at Harvard Medical School, have for the first time synthesized ribosomes -- cell structures responsible for generating all proteins and enzymes in our bodies -- from scratch in a test tube.
Others have previously tried to synthesize ribosomes from their constituent parts, but the efforts have yielded poorly functional ribosomes under conditions that do not replicate the environment of a living cell. In addition, attempts to combine ribosome synthesis and assembly in a single process have failed for decades.
Michael C. Jewett, a synthetic biologist at Northwestern, George M. Church, a geneticist at Harvard Medical School, and colleagues recently took another approach: they mimicked the natural synthesis of a ribosome, allowing natural enzymes of a cell to help facilitate the human-made construction.
The technology could lead to the discovery of new antibiotics targeting ribosome assembly an advanced understanding of how ribosomes form and function and the creation of tailor-made ribosomes to produce new proteins with exotic functions that would be difficult, if not impossible, to make in living organisms.
"We can mimic nature and create ribosomes the way nature has evolved to do it, where all the processes are co-activated at the same time," said Jewett, who led the research along with Church. "Our approach is a one-pot synthesis scheme in which we toss genes encoding ribosomal RNA, natural ribosomal proteins, and additional enzymes of an E. coli cell together in a test tube, and this leads to the construction of a ribosome."
Jewett is an assistant professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and Applied Science.
The in vitro construction of ribosomes, as demonstrated in this study, is of great interest to the synthetic biology field, which seeks to transform the ability to engineer new or novel life forms and biocatalytic ensembles for useful purposes.
The findings of the four-year research project were published June 25 in the journal Molecular Systems Biology.
Comprising 57 parts -- three strands of ribonucleic acid (RNA) and 54 proteins -- ribosomes carry out the translation of messenger RNA into proteins, a core process of the cell. The thousands of proteins per cell, in turn, carry out a vast array of functions, from digestion to the creation of antibodies. Cells require ribosomes to live.
Jewett likens a ribosome to a chef. The ribosome takes the recipe, encoded in DNA, and makes the meal, or a protein. "We want to make brand new chefs, or ribosomes," Jewett said. "Then we can alter ribosomes to do new things for us."
"The ability to make ribosomes in vitro in a process that mimics the way biology does it opens new avenues for the study of ribosome synthesis and assembly, enabling us to better understand and possibly control the translation process," he said. "Our technology also may enable us in the future to rapidly engineer modified ribosomes with new behaviors and functions, a potentially significant advance for the synthetic biology field."
The synthesis process developed by Jewett and Church -- termed "integrated synthesis, assembly and translation" (iSAT) technology -- mimics nature by enabling ribosome synthesis, assembly and function in a single reaction and in the same compartment.
Working with E. coli cells, the researchers combined natural ribosomal proteins with synthetically made ribosomal RNA, which self-assembled in vitro to create semi-synthetic, functional ribosomes.
They confirmed the ribosomes were active by assessing their ability to carry out translation of luciferase, the protein responsible for allowing a firefly to glow. The researchers then showed the ability of iSAT to make a modified ribosome with a point mutation that mediates resistance to the antibiotic clindamycin.
The researchers next want to synthesize all 57 ribosome parts, including the 54 proteins.
"I'm really excited about where we are," Jewett said. "This study is an important step along the way to synthesizing a complete ribosome. We will continue to push this work forward."
Jewett and Church, a professor of genetics at Harvard Medical School, are authors of the paper, titled "In Vitro Integration of Ribosomal RNA Synthesis, Ribosome Assembly, and Translation." Other authors are Brian R. Fritz and Laura E. Timmerman, graduate students in chemical and biological engineering at Northwestern.
The work was carried out at both Northwestern University and Harvard Medical School.