Praise God Through Jesus Christ for Rare Proteins

[womanatwell]

Praise God for Rare Proteins (1 of 3)

Hi. Before CAF ends, I’d like to explain some scientific (technical) facts about the underlying biology of God’s living Creation. They point to the wonder of life.

It has been 30 years since a major scientific article about proteins was published by researchers. One of these scientists is Robert T. Sauer, Salvador E. Luria Professor of Biology at MIT. He has a BA from Amherst in biophysics and a PhD from Harvard. The paper and the findings are technical and unfortunately the most interesting fact is behind a paywall, but I will attempt to give a short explanation. The paper is: JF Reidhaar-Olson and RT Sauer, “Functionally acceptable substitutions in two alpha-helical regions of lambda repressor,” Proteins , 7, 4 (1990): 306-16. From here I will refer to the article as RO&S, and the abstract can be found in the paper title link at the NCBI PubMed website. NCBI stands for National Center for Biotechnology Information.
(Please Note: This uploaded content is no longer available.)

The Lambda phage is a virus that infects bacteria, in this case E. coli, and it has a protein called “repressor.” I have included an image of repressor (purple) next to a DNA strand, from Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB). More information on this protein is at RCSB entry 3BDN.

Proteins are made within the cell, the basic unit of biology, of every living organism. DNA codes for proteins, which do much of the work of the specific cells. The alpha helical regions to which the RO&S paper refer are among the particular parts of proteins that give them their function. The lambda repressor was the protein they were researching, although they used just part of the protein for the experiments. The substitutions in the title refer to the subunits of proteins, called amino acids. There are 20 kinds of these in most proteins and each is made of a certain set of atoms. The researchers wanted to see how many amino acids could be interchanged with the parts of the protein still remaining functional. They used an experimental method to make random substitutions in these subunits within the repressor protein. The amino acids are numbered and they used two sets: 8-23 and 75-83 (Using 1-92 amino acids of a 237 amino acid protein).

I will use the term “permutation” here, meaning the evaluation of proteins must include specific order of amino acids and their repetition, unlike “combination” which does not require a specific order. (Protein probabilities are different than card game deals and yield very different numbers.) RO&S reveals that though there are a large number of subunit permutations which can make working protein folds similar to the particular one they studied, the proportion of functional ones of possible permutations are only about 1 in 10^63. 10^63 is the number 1 with 63 0’s following it.
(Please Note: This uploaded content is no longer available.)

 

[womanatwell]

Protein Rarity (2 of 3)

Other scientists have verified the findings of JF Reidhaar-Olson and RT Sauer, and for short proteins a round-off number of the proportion of short functional proteins could be about 1 in 10^70.

As scientists discover the DNA gene (and thereby protein) codes of more and more species, they are finding a certain percentage of each, around 10% to 30%, are not related to any other species. These as a group are known, among other names, as orphan, or ORFan genes (ORF for Open Reading Frame—the part of the DNA that is copied). Among the many scientific papers that have been reporting this finding is by Arendsee, Li, and Wurtele, “Coming of age: orphan genes in plants,” Trends in Plant Science 19, 11 (Nov. 2014): 698-708. The first sentence of the paper’s abstract says: “Sizable minorities of protein-coding genes from every sequenced eukaryotic and prokaryotic genome are unique to the species.” Eu- and pro-karyotic stand for different types of cells which make up all living systems.

The mutation rates of bacteria are less than 1 per generation and for humans less than 100 per generation. When we speak of related proteins, it means they could have come about naturally due to mutation rates of DNA and selection from the numbers of existing populations. Related proteins are found throughout life.

But these ORFans are unrelated, mathematically separated from all others. They are unique to the various types and species of life, perhaps giving them their very properties for biological diversity.

There is a limit for whether DNA mutations and subsequent selection could have produced life and our wide variety of genes. Fredric P. Nelson calculated the maximum number of organisms that could have existed on the Earth by water volume in 4 billion years at about 10^50. This whole paper is available online. Example #2 on page 31 shows his calculations. The link is here for Fredric P. Nelson, “Needed: A New Vocabulary for Understanding Evolution,” Perspectives on Science and Christian Faith 58, 1 (March 2006): 28-36. (Water volume is estimated to have stayed the same in the Earth’s history even at 4 billion years.)

The chances that random strings of amino acids are or will realistically become working are vanishingly small due to the extremely small proportion which are functional, as shown by Reidhaar-Olson and Sauer, among others, as discussed above

 

[womanatwell]

Protein Rarity (3 of 3)

Pertaining to both origin and evolution, N. Tokuriki and D. Tawfik researched protein stability in terms of thermodynamics and kinetics. They found only a few substitutions could be tolerated before the proteins became severely impeded in their function. Though there can be compensation, this strictly limits any ease of evolution. The article is N. Tokuriki and D. Tawfik, “Stability effects of mutations and protein evolvability,” Current Opinion in Structural Biology 19, 5 (Oct. 2009): 596-604.

Concerning life’s origin, a minimal, natural free-living organism (not parasites or lab creatures which are given nutrients) has been estimated to need around 1000 proteins to survive by NCBI researchers Koonin and Wolf, “Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world,” Nucleic Acids Research 36, 21 (Dec. 2008): 6688-6719. Even if some proteins somehow became functional and were closely related, the probability for each try of compositions of 10% (100) unrelated functional proteins for this size of organism is figured by taking each of the 100 independently and multiplying, leading to a probability of 1 in 10^7000 (a 1 with 7,000 zeroes following it).

Many considered the sections between genes on DNA as “junk,” but these are becoming recognized as important parts that regulate gene expression in growth, hormone metabolism and the like. The DNA of humans holds about 3 billion base pairs per most of our tiny 75 trillion cells. The base pairs are specific molecules much like the amino acids of the proteins (short description at genome.gov HERE). Proteins called histones and related parts wrap and unwrap the DNA so it can be used (short description at genome.gov HERE). It is mind-boggling that it all works together so that our bodies can develop and metabolize.

We are discovering how rare proteins are. No matter how God made life, we can see it is extremely complex. The more we know about it, the more we will understand what a marvel it is.

Let us praise the Lord, through Jesus Christ, for His Creation.

NCBI Policies HERE.

Citation for RCSB: Helen M. Berman, John Westbrook, Zukang Feng, Gary Gilliland, T. N. Bhat, Helge Weissig, Ilya N. Shindyalov, Philip E. Bourne, “The Protein Data Bank,” Nucleic Acids Research 28, 1 (Jan. 1, 2000): 235–242.