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Tuesday, October 31, 2017

The history of DNA sequencing

This year marks the 40th anniversary of DNA sequencing technology (Gilbert and Maxam, 1977; Sanger et al., 1977)1 The Sanger technique soon took over and by the 1990s it was the only technique used to sequence DNA. The development of reliable sequencing machines meant the end of those large polyacrylamide gels that we all hated.

Pyrosequencing was developed in the mid 1990's and by the year 2000 massive parallel sequencing using this technique was becoming quite common. This "NextGen" sequencing technique was behind the massive explosion in sequences in the early part of the 21st century.2

Even newer techniques are available today and there's a debate about whether they should be called Third Generation Sequencing (Heather and Chain, 2015).

Nature has published a nice review of the history of DNA sequencing (Shendure et al., 2017). I recommend it to anyone who's interested in the subject. The figure above is taken from that article.


1. Many labs were using the technology in 1976 before the papers were published.

2. New software and enhanced computer power played an important, and underappreciated, role.

Heather, J.M., and Chain, B. (2015) The sequence of sequencers: The history of sequencing DNA. Genomics, 107:1-8. [doi: 10.1016/j.ygeno.2015.11.003]

Maxam, A.M., and Gilbert, W. (1980) Sequencing end-labeled DNA with base-specific chemical cleavages. Methods in enzymology, 65:499-560. [doi: 10.1016/S0076-6879(80)65059-9]

Sanger, F., Nicklen, S., and Coulson, A.R. (1977) DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, 74:5463-5467. [PDF]

Shendure, J., Balasubramanian, S., Church, G.M., Gilbert, W., Rogers, J., Schloss, J.A., and Waterston, R.H. (2017) DNA sequencing at 40: past, present and future. Nature, 550:345-353. [doi: 10.1038/nature24286]


Escape from X chromosome inactivation

Mammals have two sex chromosomes: X and Y. Males have one X chromosome and one Y chromosome and females have two X chromosomes. Since females have two copies of each X chromosome gene, you might expect them to make twice as much gene product as males of the same species. In fact, males and females often make about the same amount of gene product because one of the female X chromosomes is inactivated by a mechanism that causes extensive chromatin condensation.

The mechanism is known as X chromosome inactivation. The phenomenon was originally discovered by Mary Lyon (1925-2014) [see Calico Cats].

Saturday, October 28, 2017

Creationists questioning pseudogenes: the GULO pseudogene

This is the second post discussing creationist1 papers on pseudogenes. The first post addressed a paper by Jeffrey Tomkins on the β-globin pseudogene [Creationists questioning pseudogenes: the beta-globin pseudogene]. This post covers another paper by Tomkins claiming that the GULO pseudogenes in various primate species are not derived from a common ancestor but instead have been deactivated independently in each lineage.

The Tomkins' article was published in 2014 in Answers Research Journal, a publication that describes itself like this:
ARJ is a professional, peer-reviewed technical journal for the publication of interdisciplinary scientific and other relevant research from the perspective of the recent Creation and the global Flood within a biblical framework.

Saturday, October 14, 2017

Creationists questioning pseudogenes: the beta-globin pseudogene

Jonathan Kane recently (Oct. 6, 2017) posted an article on The Panda's Thumb where he claimed that Young Earth Creationists often don't get enough credit for raising serious issues about evolution [Five principles for arguing against creationism].

He mentioned some articles about pseudogenes as prime examples. I asked him for references and he responded with two articles by Jeffrey Tomkins that were published on the Answers in Genesis website. The first was on the β-globin pseudogene and the second was on the GULO pseudogene. Both articles claim that these DNA sequences aren't really pseudogenes because they have functions.

I'll deal with the β-globin pseudogene in this post and the GULO pseudogene in a subsequent post.

Wednesday, October 11, 2017

Historical evolution is determined by chance events

Modern evolutionary theory is based on the idea that alleles become fixed in a population over time. They can be fixed by natural selection if they confer selective advantage or they can be fixed by random genetic drift if they are nearly neutral or slightly deleterious [Learning about modern evolutionary theory: the drift-barrier hypothesis]. Alleles arise by mutation and the path that a population follows over time depends on the timing of mutations [Mutation-Driven Evolution]. That's largely a chance event.