acetyl-CoA + H2O + oxaloacetate → citrate + HS-CoA + H+We usually think of this reaction in terms of energy production since acetyl-CoA is the end product of glycolysis and the citric acid cycle produces substrates that enter the electron transport system leading to production of ATP. However, it's important to keep in mind that the enzyme also catalyzes the reverse reaction.
For decades, the miniscule protein-coding portion of the genome was the primary focus of medical research. The sequencing of the human genome showed that only ∼2% of our genes ultimately code for proteins, and many in the scientific community believed that the remaining 98% was simply non-functional “junk” (Mattick and Makunin, 2006; Slack, 2006). However, the ENCODE project revealed that the non-protein coding portion of the genome is copied into thousands of RNA molecules (Djebali et al., 2012; Gerstein et al., 2012) that not only regulate fundamental biological processes such as growth, development, and organ function, but also appear to play a critical role in the whole spectrum of human disease, notably cancer (for recent reviews, see Adams et al., 2017; Deveson et al., 2017; Rupaimoole and Slack, 2017).Cell is a high-impact, refereed journal so we can safely assume that this paper was reviewed by reputable scientists. This means that the view expressed in the paragraph above did not raise any alarm bells when the paper was reviewed. The authors clearly believe that what they are saying is true and so do many other reputable scientists. This seems to be the "standard" view of junk DNA among scientists who do not understand the facts or the debate surrounding junk DNA and pervasive transcription.
Slack, F.J. and Chinnaiyan, A.M. (2019) The Role of Non-coding RNAs in Oncology. Cell 179:1033-1055 [doi: 10.1016/j.cell.2019.10.017]
It's difficult to know how many protein-coding genes there are in the human genome because there are several different ways of counting and the counts depend on what criteria are used to identify a gene. Last year I commented on a review by Abascal et al. (2018) that concluded there were somewhere between 19,000 and 20,000 protein-coding genes. Those authors discussed the problems with annotation and pointed out that the major databases don't agree on the number of gene [How many protein-coding genes in the human genome?].
This is the 2019 Killian lecture at MIT, delivered in April 2019 by Gerald Fink. Fink is an eminent scientist who has done excellent work on the molecular biology of yeast. He was director of the prestigious Whitehead Institute at MIT from 1990-2001. With those credentials you would expect to watch a well-informed presentation of the latest discoveries in molecular genetics. Wouldn't you?
I'm a big fan of Richard Lenski's long-term evolution experiment (LTEE) and of Zachary Blount's work in particular. [Strolling around slopes and valleys in the adaptive landscape] [On the unpredictability of evolution and potentiation in Lenski's long-term evolution experiment] [Lenski's long-term evolution experiment: the evolution of bacteria that can use citrate as a carbon source]
The results of the LTEE raise some interesting questions about evolution. The Lenski experiment began with 12 (almost) identical cultures and these have now "evolved" for 31 years and more than 65,000 generations. All of the cultures have diverged to some extent and one of them (and only one) has developed the ability to use citrate as a carbon source. Many of the cultures exhibit identical, or very similar, mutations that have reached significant frequencies, or even fixation, in the cultures.A paper announcing the first complete sequence of a human chromosome has recently been posted on the bioRxiv server.
Miga, K. H., Koren, S., Rhie, A., Vollger, M. R., Gershman, A., Bzikadze, A., Brooks, S., Howe, E., Porubsky, D., Logsdon, G. A., et al. (2019) Telomere-to-telomere assembly of a complete human X chromosome. bioRxiv, 735928. doi: [doi: 10.1101/735928]
Abstract: After nearly two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no one chromosome has been finished end to end, and hundreds of unresolved gaps persist. The remaining gaps include ribosomal rDNA arrays, large near-identical segmental duplications, and satellite DNA arrays. These regions harbor largely unexplored variation of unknown consequence, and their absence from the current reference genome can lead to experimental artifacts and hide true variants when re-sequencing additional human genomes. Here we present a de novo human genome assembly that surpasses the continuity of GRCh38, along with the first gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome, we reconstructed the ∼2.8 megabase centromeric satellite DNA array and closed all 29 remaining gaps in the current reference, including new sequence from the human pseudoautosomal regions and cancer-testis ampliconic gene families (CT-X and GAGE). This complete chromosome X, combined with the ultra-long nanopore data, also allowed us to map methylation patterns across complex tandem repeats and satellite arrays for the first time. These results demonstrate that finishing the human genome is now within reach and will enable ongoing efforts to complete the remaining human chromosomes.
It's been more than seven years since I posted information on how much of the human genome has been sequenced [How Much of Our Genome Is Sequenced?]. At that time, the latest version of the human reference genome was GRCh37.p7 (Feb. 3, 2012) and 89.6% of the genome had been sequenced. It's time to update that information.
We have a pretty good idea of the size of the human genome based on quantitative Feulgen staining (1940-1980) and reassociation kinetic experiments from the 1970s (Morton, 1991). We can safely assume that the correct size of the human genome is close to 3,200,000,000 bp (3,200,000 kb, 3,200 Mb, 3.2 Gb) [How Big Is the Human Genome?]. That's the value cited most often in the literature. However, the actual values calculated by Morton (1991) were 3.227 Gb for the haploid female genome and less than that for the haploid male genome. The human reference genome contains all 22 autosomes plus one copy of the X chromosome and one copy of the Y chromosome. This gives a total of 3.286 Gb.
This the last of a series of posts by Arlin Stoltzfus on the role of mutation as a dispositional factor in evolution. Arlin has established that the role of mutation in evolution is much more important than most people realize. He has also built a strong case for the influence of mutation bias. How should we incorporate these concepts into modern evolutionary theory?
Click on the links in the box (below) to see the other posts in the series.
This is part of a continuing series of posts by Arlin Stoltzfus on the role of mutation as a dispositional factor in evolution. In this post, Arlin explains how defenders of the Modern Synthesis react in the face of serious challenges to the theory that was formulated in the 1940s and 50s. Rather than reject the theory, they engage in various forms of "synthesis apologetics."
Click on the links in the box (below) to see the other posts in the series.
This is part of a continuing series of posts by Arlin Stoltzfus on the role of mutation as a dispositional factor in evolution. In this post Arlin discusses his view of neo-Darwinism and why it is inconsistent with macromutations and lateral gene transfer. He equates neo-Darwinism with the Modern Synthesis (1959 version), a comparison that might be challenged. Click on the links in the box (below) to see the other posts in the series.
I was checking out the science books in our local bookstore the other day and I came across Evolution 2.0 by Perry Marshall. It was published in 2015 but I don't recall seeing it before.
The author is an engineer (The Salem Conjecture) who's a big fan of Intelligent Design. The book is an attempt to prove that evolution is a fraud.This is part of a continuing series of posts by Arlin Stoltzfus on the role of mutation as a dispositional factor in evolution. In this post Arlin discusses the role of adaptation and what determines the pathway that it will take over time. Is it true that populations will always adapt quickly to any change in the environment? (Hint: no it isn't!) Click on the links in the box (below) to see the other posts in the series.
This is the ninth in a series of guest posts by Arlin Stoltzfus on the role of mutation as a dispositional factor in evolution. Click on the links in the box (below) to see the other post in the series.
"Darwin discovered the great principle which rules the evolution of organisms. It is the principle of natural selection. It is the sifting out of all organisms of minor worth through the struggle for life. It is only a sieve, and not a force of nature" (p. 6)Morgan (1916), in his closing summary, writes:
"Evolution has taken place by the incorporation into the race of those mutations that are beneficial to the life and reproduction of the organism" (p. 194)
