A Journey Through Time: The Evolution of DNA

4.5 billion years ago, Earth was a vastly different place. Geologists named this time period the Hadean Era (Fig. 1) after Hades, the Greek God of the Underworld. Just like the Underworld, Earth during the Hadean Era was hellish. In its early stages, the newly formed Earth was unstable, with temperatures of up to 230°C! Volcanic eruptions and asteroid impacts occurred frequently, and there were entire seas made of magma. There was water on earth, but it existed as water vapour due to the intense heat [1]. Imagine living inside a giant kettle, with lava and asteroids to dodge - not the most welcoming place to live, right?

If you agree, then you’ve got something in common with the earliest life on Earth: during the early Hadean Era, life hadn’t evolved yet. The earliest undisputed evidence of life on Earth is a 3.5 billion years old rock, which once contained microorganisms, although some studies place our last universal common ancestor closer to 4 billion years ago [1]! The question is: when, and how, did life on Earth evolve?

Figure 1: Artist's impression of the Hadean Eon. Credit: Tim Bertelink/CC BY-SA

All living organisms have DNA genomes. DNA, or deoxyribonucleic acid, is a double-stranded macromolecule which stores an organism’s genetic information as a code made up of four chemical bases: adenine (A), thymine (T), cytosine (C) and guanine (G). It acts like a genetic recipe book - the order in which these four bases appear on the DNA strand determines which proteins the cell will synthesise. The building blocks of DNA are known as nucleotides; they are composed of a phosphate group, deoxyribose sugar, and a nitrogenous base (either A, T, C or G) [2]. Understanding how DNA evolved is, therefore, a key step in understanding the origin of life on Earth. 

Scientists don’t yet have a full picture of abiogenesis - the original process by which life evolved from non-living matter - however, most researchers currently believe that life evolved from an ‘RNA world’.

The RNA World Hypothesis

RNA, or ribonucleic acid, is a macromolecule which can store and replicate genetic information, just like DNA. Structurally, it is very similar to DNA, however, there are some key differences: RNA is usually single-stranded, it contains ribose rather than deoxyribose sugar, and while it uses the three DNA bases adenine, cytosine and guanine, its fourth base is uracil (U) rather than thymine. DNA is much more stable than RNA and can grow much longer, which is likely why life on Earth evolved to be DNA-based, although RNA performs important functions in many organisms too [3].

Towards the end of the Hadean Era, Earth wasn’t quite so ‘hellish’: its surface temperature had finally fallen below boiling point, and much of the atmospheric water vapour had now condensed forming oceans which separated rocky continents [4]. Although life didn’t exist yet, scientists hypothesise that all of the organic compounds necessary for living organisms would have been present in some areas of warm water, this is known as ‘primordial (ancient) soup’ [5]. Amongst these organic compounds were free-floating nucleotides, specifically A, U, C and G, regularly forming bonds with each other in the primordial soup which often quickly broke down. Certain random sequences of nucleotides would stay bonded longer than others, and over time longer strands began to assemble, with new bonds forming more quickly than old bonds were broken down. Some of these emerging RNA strands had catalytic properties, which could assist in the replication and formation of new RNA strands. Eventually, RNA chains that could catalyse the bonding of amino acids into polypeptide chains (the precursor molecules to proteins) developed [6].

Science would not be science without experiments, and despite its 4 billion-year-old history, abiogenesis research is no exception. The first significant experiment which investigated the chemical origin of life is known as the Miller-Urey experiment. It was first conducted in 1952, and it simulated the conditions thought to be present on Earth around the time that life first arose, therefore investigating how it might have done so. Using only simple chemical compounds - water, methane, ammonia and hydrogen - Stanley Miller and Harold Urey managed to synthesise many of the amino acids that are crucial to organisms today. Abiogenesis research has progressed much further since 1952 and the Miller-Urey experiment has been adapted to include different conditions and a wider range of chemicals now believed to have been present. More modern experiments have even evidenced potential mechanisms for the nucleotide precursors of RNA thought to have been present in the primordial soup of the late Hadean era [7].

If the RNA hypothesis is correct, it was likely followed by an intermediate ‘RNP world’. RNPs (ribonucleoproteins) are proteins that are structurally associated with RNA; they perform key biological functions, such as, ribosomes performing protein synthesis, and telomerases preventing DNA damage at the ends of chromosomes. These RNPs are likely to have been much more stable than RNA alone; this is because the peptides coating the RNA strand can prevent its bonds from breaking as easily. The added stability and complexity of RNPs would have made them better enzyme candidates than RNA alone and therefore able to perform more intricate reactions [8, 9].

Scientists are still puzzled over the exact circumstances which may have caused the transition from RNA to DNA. Viruses and living organisms today use enzymes, called reverse transcriptases, to synthesise complementary DNA strands. Like their RNA precursors, these DNA strands could store genetic information. DNA benefited from the enzymatic properties of the RNPs, which it could use to replicate and synthesise proteins. DNA, which was originally an underdog in the RNA-world hypothesis, outcompeted its predecessor for many reasons:

•  It was more stable.

•  It could be repaired more easily and more accurately.

•  It was capable of making much larger genomes, with much more information; DNA required this complexity in order to transition from simply chemically active molecules to genetic material capable of synthesising entire living organisms.

• DNA strands could grow much larger than RNA strands. In fact, you can stretch out the DNA present in one cell of your body and it would be about 6ft long! [10].

LUCA, our Last Universal Common Ancestor

We’ve come a long way from when our great great great great great great great (you get where I’m going here) RNA grandparents were first synthesised in a big warm ocean-sized bowl of primordial soup. But what was our earliest living ancestor? When did DNA make that crucial jump from simply being a chemically active molecule to being the genetic recipe for a living organism?

It is thought that all living organisms - plants, animals, fungi, bacteria and archaea - are descended from an organism called LUCA (the Last Universal Common Ancestor). Scientists don’t necessarily think LUCA was the first life on Earth, but instead the only organism of its time that still has living descendants. There is some conflicting evidence for when LUCA might have first lived, but it seems to have been roughly four billion years ago. Evidence suggests that it might have lived in hot, deep-sea hydrothermal vents. It was anaerobic, which is useful seeing as Earth’s atmosphere contained almost no oxygen, and it was autotrophic, meaning it made its own food from the simple inorganic materials in its environment, such as carbon dioxide, hydrogen, and nitrogen [11].

A 2016 study by Martin et al., which compared the genomes of many different living organisms, found 355 different genes likely to have been present in LUCA; geneticists can use information like this to investigate LUCA’s biochemistry [12]. There isn’t much of a family resemblance between us and LUCA - it is thought to have been a small, single-celled organism, with a circular DNA coil floating freely in its cytoplasm. However, we have inherited some key traits from LUCA: it likely had a double-stranded DNA genome, using the same A, C, G and T bases as living organisms today. Its genetic code was used to synthesise proteins, using the familiar methods of mRNA transcription and translation at the ribosome [13].

It is mind-blowing to think that all life on Earth can be traced back to this single-celled, anaerobic microorganism that lived in hydrothermal vents around four billion years ago. It is even more mind-boggling to think that a few million years before that, life on Earth didn’t exist at all! Meanwhile, in Earth’s hot seas, molecules that are only visible using electron microscopes, were bonding, breaking, and catalysing what would soon come to be a legacy of around four billion years of DNA-based life on Earth… and counting!

References

[1] C. Johnson, M. D. Affolter, P. Inkenbrandt, C. Mosher, ‘8.3 Hadean Eon’ in An Introduction to Geology [online], https://geo.libretexts.org/Bookshelves/Geology/Book%3A_An_Introduction_to_Geology_(Johnson%2C_Affolter%2C_Inkenbrandt%2C_and_Mosher)/08%3A_Earth_History/8.03%3A_Hadean_Eon [accessed 5 July 2020].

[2] ‘DNA’ in Encyclopaedia Britannica [online], https://www.britannica.com/science/DNA [accessed 5 July 2020].

[3] ‘RNA’ in Encyclopaedia Britannica [online], https://www.britannica.com/science/RNA [accessed 5 July 2020].

[4] ‘Hadean Eon’ in Encyclopaedia Britannica [online], https://www.britannica.com/science/Hadean-Eon [accessed 5 July 2020].

[5] C. Weidemann, ‘Is the Origin of Life a Fluke? Why the Chance Hypothesis Should Not be Dismissed Too Quickly’ in What is Life? On Earth and Beyond (Cambridge: Cambridge University Press, 2017), pp. 132-155.

[6] L. Orgel, ‘Prebiotic Chemistry and the Origin of the RNA World’ in Critical Reviews in Biochemistry and Molecular Biology, 39.2 (2010), pp. 99-123.

[7] M. Ferus et al., ‘Formation of nucleobases in a Miller-Urey reducing atmosphere’ in PNAS, 114.17 (2017), pp. 4306-4311.

[8] T. Cech, ‘The RNA Worlds in Context’ in CSH Perspectives in Biology, 4.7 (2012).

[9] T. Cech, ‘Crawling Out of the RNA World’ in Cell, 136.4 (2009), pp. 599-602.

[10] P. Forterre et al., ‘Origin and Evolution of DNA and DNA Replication Machineries’, in Madame Curie Bioscience Database [online], https://www.ncbi.nlm.nih.gov/books/NBK6360/ [accessed 6 July 2020].

[11] K. Cooper, ‘Looking for LUCA, the Last Universal Common Ancestor’ in Phys.org [online], https://phys.org/news/2018-12-luca-universal-common-ancestor.html [accessed 6 July 2020].

[12] W. Martin. et al., ‘Physiology, Phylogeny and LUCA’, in Microbial Cell, 3.12 (2016), pp. 582-587.

[13] E. Koonin et al., ‘The Replication Machinery of LUCA: Common Origin of DNA Replication and Transcription’ in BMC Biology, 18.61 (2020).