A biochemist examines imaginative claims about natural selection creating a new gene.Did a New Gene Arise by Darwinian Selection?by Dr Ross Anderson*Dr. Anderson critiques a paper by Zhuang et al., “Molecular mechanism and history of non-sense to sense evolution of antifreeze glycoprotein gene in northern gadids” (PNAS, 13 Feb 2019), which claims a new antifreeze gene in Arctic cod arose by ‘fortuitous’ chance events and natural selection.“This paper is a concrete dissection of the process of a de novo gene birth that has conferred a vital adaptive function directly linked to natural selection.”Summary: The authors report here the putative assembly (evolution) of a gene encoding an antifreeze glycoprotein (AFGP) in cod fish. Comparing DNA sequences of AFGP-producing gadids with sequences from non-AGFP-producing gadids the authors believe they have identified a sequence in the non-AFGP gadids that doesn’t appear to code for a protein, but with a little imagination can be made into a gene which encodes an AFGP.Starting with Something, Not NothingSo, let’s see, here we have a fully formed, functional AFGP gene. As such it has all the components necessary for expression and regulation. We want to try and understand just how this gene could have arisen from a non-coding sequence; i.e., how it arose de novo. The authors recognize that most genes supposedly have arisen from pre-existing genes, but that new genes from non-coding sequences is rare, but theoretically possible. Reported here is a possible example of such a de novo gene.Examination of extant AFGPs reveals that they are typically composed of a short sequence of amino acids repeated many times; e.g., the tripeptide, Thr-Ala-Ala (threonine, alanine, alanine), repeated n times. Some of the Thr residues have been glycosylated; i.e., they have sugars added to a side-chain.The paper is an interesting read in that it reveals the very creative imagination of some scientists.Proteins are coded by triplet codons of DNA “letters” A, C, T, and G. (Illustra Media)Let’s use our creative imagination and see if we can construct a gene that encodes such a protein. First, we find some DNA sequences in gadids that are somewhat similar, but do not encode a protein; they are non-coding sequences. Compare these sequences with the target AFGP gene sequence and see what is needed to make these non-coding sequences match the target AFGP sequence. We notice that what we need is for the coding region to encode a polyprotein composed of the repeated amino acid sequence Thr-Ala-Ala. We find the DNA sequence GCA, which is an Ala codon, repeated 9 times to generate a 27-nucleotide (nt) sequence. In the target AFGP gene the Thr-Ala-Ala repeat is found bounded by two 27-nt (nucleotide) repeats. So, let’s propose that the sequence of 27 nucleotides (GCA repeated 9 times) in the “ancestral” sequence underwent a chance duplication event to generate two 27-nt repeats. Then propose a second chance duplication event to generate four such repeats.Blindly Aiming for the TargetExamination of the target AFGP amino acid sequence shows we need a Thr codon in the midst of the 27-nt repeats. Suppose we substitute an ‘A’ for the ‘G’ in one of the GCA sequences. The new 9-nt sequence would then read ACAGCAGCA which, when translated, would generate the required Thr-Ala-Ala sequence. Now that we have the appropriate coding sequence, we need to have it repeated as the target amino acid sequence, Thr-Ala-Ala, is repeated many times. So, let’s propose that this new 9-nt sequence is also duplicated many times.We also notice that in the functional AFGP gene there are scattered arginine and glutamine codons. Presumably when translated these will provide signals for a protease to hydrolyze the polypeptide into many shorter peptides which are the antifreeze proteins. To generate these two amino acid codons in a sea of GCA codons would require at a minimum two strategically placed substitutions in a GCA codon to generate either an arginine codon or a glutamine codon. The authors provide no explanation for how these substitutions nicely provide codons for only these two amino acids when codons for many other amino acids could be generated more easily with just one substitution. The magic is all done by chance and natural selection in six fortuitous steps. Here is the summary diagram of their model from the paper:Fig. 4Evolutionary mechanism of the gadid AFGP gene from noncoding DNA. The color codes of the sequence components follow Fig. 1. (A) The ancestral noncoding DNA contained latent signal peptide-coding exons with a 5′ Kozak motif, adjacent to a duplication-prone 27-nt GCA-rich sequence. (B) The 27-nt GCA(Ala)-rich sequence duplicated forming four tandem copies. (C) A 9-nt in the midst of the four 27-nt duplicates became the three codons for one AFGP Thr-Ala-Ala unit and underwent microsatellitelike duplication forming a proto-ORF. A proximal upstream regulatory region acquired through a putative translocation event. (E) A 1-nt frameshift led to a contiguous SP, a propeptide, and a Thr-Ala-Ala-like cds in a read-through ORF [open reading frame]. (F) Intragenic (Thr-Ala-Ala)n cds amplification, fulfilling the antifreeze function under natural selection.Signalling the BlindNow we have essentially constructed the coding region, but we’re not finished yet. All AFGPs are secreted proteins and as such require that a signal peptide sequence be attached to the coding region. The DNA sequence which encodes this signal has to be added to our coding sequence. It just so happens that the “ancestral” sequence has such a sequence in just the correct place with respect to the coding region. Only one problem, there is a single nucleotide which does not allow the signal sequence to be in the proper reading frame to the coding region. Let’s propose that this one nucleotide was deleted causing a reading frame-shift which then directly linked the signal sequence with the coding sequence. Interestingly, the authors indicate that DNA region encoding the signal sequence somehow develops an intron-exon structure, but no explanation is given.Promoting Chance to Commander of the FortuitousWe’re still not finished. We need a promoter region added to our new gene. Without a proper promoter, a gene will not be transcribed into an mRNA, and thus no protein product. The authors propose that “fortuitously”, a translocation event took place and the promoter from another gene was added in the exact location where needed. This proposed translocation also provided a 5′-untranslated region (UTR) in perfect alignment with the signal sequence as to save the reading frame generated earlier.All functional AFGP genes also have a 3′-UTR. One species of gadid lacks a 3′-UTR and is a putative pseudogene, suggesting that sequences in the 3′-UTR are necessary for expression. In the paper the authors add a 3′-UTR, but do not explain where it came from as it is not found in the putative ancestral sequence.Imaginative Storytelling Masquerading as ScienceThe paper is an interesting read in that it reveals the very creative imagination of some scientists. It is likened to examining a functioning car noting was is needed and going to a junkyard and auto parts store looking for all the pieces that could be cobbled together to make another functional car.Now, sequence comparisons can provide valuable information, however, when trying to construct an evolutionary story of how a gene might have arisen de novo, one must bear in mind that all is hypothetical as there is no real way to experimentally test the conclusions of such hypothesizing. In short, it amounts to just storytelling.The authors may have been able to come up with a more realistic explanation for the loss of function rather than try to explain a gain in function, but that would not have been as interesting or as much fun, and it certainly would not have been published.Note: for those interested in this subject, Dr. Cornelius Hunter, another biochemist, has critiqued the PNAS paper at Evolution News & Science Today. A related, but different claim about gene evolution from 2011 was analyzed by Shaun Doyle in the Journal of Creation (CMI).*About the authorDr. Anderson’s expertise is in the area of biochemistry and molecular biology. He has taught Biochemistry and helped to direct research projects of graduate and medical students at Baylor College of Medicine, Houston, TX. Dr. Anderson was a post-doctoral researcher in the Molecular Genetics Division of the Department of Ophthalmology at the Houston Neurosensory Center.Dr. Anderson was a member of both the undergraduate and graduate faculty at Lamar University, Beaumont, TX. There he taught and directed the research activities of undergraduates and Masters of Science degree candidates in Biology. Currently he is professor of biochemistry at The Master’s University in southern California.Dr. Anderson’s research interests include structure-function studies of DNA polymerizing enzymes and the synthesis and expression of synthetic human genes in bacterial hosts. He has authored or co-authored several publications in major, peer-reviewed journals. He is a member of the American Chemical Society and Sigma Xi Research Society.It’s an honor to have Dr Ross Anderson contribute this article to Creation-Evolution Headlines. Now, we end with a pictorial summary of Darwinian evolution by J. Beverly Greene. 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Before the e-reader wars, Amazon’s Kindle and Barnes & Noble’s Nook e-readers were $259. Then B&N dropped the Nook to $199 and lowering its lower-end Wi-Fi version to $149. Amazon then dropped the Kindle’s price to $189. All the while, Borders stood in the background paring its nails. Border’s e-reader, the Kobo, has stayed steady at $149.99 and its smaller version, the Libre, at $119. Borders believes that’s the right place for the e-reader to be. Related Posts Tags:#E-Books#web curt hopkins “According to Boston Consulting Group, high prices continue to be a barrier to eReader adoption. The consumer sweet spot for eReader cost (is) between $100 and $150. This positions Borders for strong consumer adoption and market penetration.” The most Borders has done in reaction to the e-reader duel is to add a little baksheesh to their offers. This morning Borders announced it was bundling the Kobo with a $20 Borders gift card, and double Borders Bucks that can be used towards a future purchase. Given that their two primary competitors are getting wise to the “sweet spot” idea, will Borders have to get its hands dirty? Before it counted on being by far the most reasonably-priced of the offerings. But what does it have if it loses that to its better known rivals? We have asked Borders and will publish an update if they respond. In the meantime, the iPad, which has sold several million in a couple of months, is despite its monthly fee, a threat for the time being. Read more ReadWriteWeb coverage of e-readers and e-books. A Web Developer’s New Best Friend is the AI Wai… Top Reasons to Go With Managed WordPress Hosting Why Tech Companies Need Simpler Terms of Servic… 8 Best WordPress Hosting Solutions on the Market
A Comprehensive Guide to a Content Audit Related Posts The Dos and Don’ts of Brand Awareness Videos Facebook is once again following in Twitter’s footsteps, this time with the announcement of new tools that allow publishers to display trending conversations and topics from the social network.The company launched two new APIs that will allow select media partners to track public posts, trending topics, and hashtags on Facebook and display them on websites and news broadcasts. Its initial media partners include Buzzfeed, CNN, NBC’s Today Show, BSkyB, Slate and Mass Relevance; Facebook said it will make the tools available to additional media and marketing partners in coming weeks. readwrite Guide to Performing Bulk Email Verification Tags:#Facebook#media#now#Trending Topics Facebook is Becoming Less Personal and More Pro…
A long, long time ago, I attended my first real sales training. The company I worked for brought 50 salespeople together for training. At one point in the day, the focus shifted to asking for an order–a single order. But I didn’t have it in me to ask for a single order. I wanted all of the business, role play or not.I was called out of the room and gently reprimanded for not following directions. The regional manager told me that it was okay that I pushed for all of the business, but that some salespeople were uncomfortable asking for a single order, and I was making them even more uncomfortable.It wasn’t until much later I understood their strategy, and it is an effective and useful tool to have in your arsenal. The strategy was to get the camel’s nose under the tent, and then work on getting the rest of the camel over time.Asking for a single order is a very small, easily obtained commitment. It isn’t a massive change. No one has to fire their present provider. Your client doesn’t have to get a committee together to make a decision.Once you have and fill an order, regardless of how small, you are no longer a salesperson. You are now a supplier, a vendor, and a potential partner. You have access to the individuals you are helping within your client account. You are in their systems. You can follow up on the small bit of work you are doing. This access gives you the opportunity to build trust, build relationships, and build future business. You do a good job, you ask for another order.You need a long term strategy to win your dream clients. But there is something to be said for gaining small commitments that open future opportunities, as long as you work like the devil to create value, earn the right to compete, and eventually establish yourself as your dream client’s partner.
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The new-look Wankhede Stadium was formally inaugurated in Mumbai on Sunday. However, it is still uncertain whether or not the stadium will be allowed to host World Cup matches.The venue is yet to receive a No Objection Certificate (NOC) from the fire department with the chief fire officer saying they will not issue the NOC unless they are fully satisfied.The stadium recently failed a fire inspection, raising concerns that it may not be ready in time for the World Cup matches.One of the main concerns raised by the fire department was the lack of access to fire brigades to all parts of the stadium. Wankhede Stadium is scheduled to host three World Cup matches including the final on April 2.ICC president and Mumbai Cricket Association chief Sharad Pawar, who formally inaugurated the stadium, refused to comment on the issue.
French swimmer Florent Manaudou shot to the Olympic 50m freestyle gold, consigning defending champion Cesar Cielo to his first major final defeat in four years. Manaudou won in 21.34 seconds, with American Cullen Jones taking the silver two tenths of a second slower on Friday.World record holder Cesar Cielo took bronze in 21.59, tapping home just five hundredths of a second behind Jones.Cielo has not been beaten in 50m since winning gold in Beijing.Asked whether he could believe he had won the gold, the 21-year-old Manaudou, the younger brother of women’s Olympic gold medallist Laure Manaudou, didn’t hesitate.”If I didn’t believe it, I wouldn’t be in an Olympic final. I was very relaxed. I think it’s the secret, being relaxed,” he said.He admitted, however, that he wasn’t sure he had the gold in the bag when he touched home.”I didn’t know. In the 50m it’s very quick, you don’t look. I saw the light come on. I knew I was going to be on the podium, which was great, but I didn’t know I would be first.”