Aug 9, 202011 min read

LUCA – The Last Universal Common Ancestor

Updated: Aug 20, 2020

“…whilst this planet has gone circling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being evolved.” – C. Darwin

Working backwards to the origin of life…

William F. Martin, Ph.D. is a former carpenter, born in Bethesda, Maryland, educated in Texas, who after hammering nails in Dallas moved to Hanover, Germany to get his degree in biology, and then to the Max-Planck Institute in Cologne for his Ph.D.

In July 2016, Madeline Weiss et al. from Martin’s lab published a paper in Nature Microbiology that worked backwards from today’s organisms to uncover what they described as the last universal common ancestor to all life on Earth – LUCA. They showed that LUCA was anerobic (did not use oxygen), obtained energy from hydrogen, converted carbon dioxide and nitrogen into essential organic compounds, and was heat loving. Extreme heat loving. They believed that LUCA originated in an environment much like the black smoker hydrothermal vents at the bottom of the ocean, discovered in 1977 by explorers in the deep-sea submersible, Alvin.

How did Martin’s group work backwards from today’s organisms to LUCA?

All life on Earth today fall into three domains, the top-most classification of living things. This three-domain classification of life was first proposed by Carl Woese in 1977 based on his discovery of a new class of what were previously thought to be bacteria.

The domain we are most familiar with are like us, eukaryotes, which are any organism made of cells with a nucleus. That covers a tremendous diversity of physical forms – everything from single celled yeast to all multicellular organisms from sponges to worms to plants to humans.

The second and possibly biggest domain are the bacteria, which are single celled, lack a nucleus, and occupy almost every environmental niche on Earth but particularly the soil and subsurface (bacteria have been found kilometers underground both on land and sea).

Eukaryotes emerge from prokaryotes — Two-domain tree of life

The third and least well-known domain is the one Woese discovered which are the archaea. Archaea look very much like bacteria, are also single-celled, and lack a nucleus. However, they are genetically more similar to eukaryotes like us. Archaea also have a unique cell surface chemistry which is very different from both bacteria and eukaryotes. Archaea are found in all places where bacteria live – but are also able to thrive in environments which are lethal to both bacteria and eukaryotes, like hot springs or salt lakes.

Key for our story about the Martin Lab’s search for LUCA, is that this three-domain classification was recently re-organized from three to two primary domains: bacteria and archaea. Close examination of core genes (genes involved in essential processing of DNA, RNA and proteins) showed that eukaryotes arose from archaea. Once upon a time, an archaeon hosted a symbiotic bacterium that eventually became the mitochondria, the power plant of the eukaryotic cell. The figure above from the Martin paper is a schematic phylogenetic tree (think of it as a family tree with LUCA as the most ancient ancestor), and illustrates the hypothesis from this two-domain model – that LUCA gave rise to the bacterial and archaeal domains, and then later the symbiotic merging of members of those two domains gave rise to eukaryotes. The previous model had LUCA giving rise to all three primary domains at once.

This two-domain classification of life gave Weiss et al. an opportunity to use big-data analytics to compare all the genomic data that scientists around the world have accumulated for the many species of bacteria and archaea.

The hunt for LUCA…

Weiss et al. looked at 1,981 complete genomes (the total compendium of genes in a given organism), of which 134 genomes were archaeal and 1,847 were bacterial.

Among the genomes of these two thousand species were 6.1 million protein-coding genes which were grouped into 286,514 protein families or clusters. Out of all those protein families, only about 11 thousand were common between both bacteria and archaea. This is important since the point behind looking for a common ancestor is that we expect descendants of a common ancestor to share homologies (common features – or genes). Therefore, the vast majority of protein coding genes were of no use to this analysis since they were unique to either bacteria or archaea. (A recent blog about evolution of the limb from fins talks a little more about homologies.)

The team then built a phylogenetic tree using algorithms that compared the amino acid sequences of the 11 thousand protein families, and grouped the ones that were the most closely related. I discussed phylogenetic trees in a previous blog. Briefly, a phylogenetic (or evolutionary) tree is like your family tree, a line drawing of the relationships between species, with an ancestor being at each branch point, and the descendants being the branches. Living organisms like us are the leaves at the very tips of the branches. The phylogenetic tree at its best is more quantitative in representation. The length of the branches denotes how far the species has diverged away from the ancestor, and two adjacent branches are more closely related to each other than more widely separate branches.

Out of 11 thousand protein families or clusters, only 355 were thought to be present in LUCA according to this analysis.

There are things that muddy the water in this neat and fancy computer analysis of biological systems. Biology is… messy. One example: our genomes are like all the things stashed in a messy attic (we can think of the attic as the nucleus – a compartment to store things – where the things are like genes). Many things/genes we have gotten from our parents, and some are unique to us. To track our ancestry, we need to filter out the things we got and only look at the things our parents gave us. Also, there might be one or two things that you might have stored for a friend, or stolen from a neighbor that clearly don’t belong to you and even has their name on it.

When a gene has been stolen from a neighbor, moved from one species to another, that is called lateral (or horizontal) gene transfer (LGT or HGT depending on the author).

Genes, especially in prokaryotes are prone to HGT. By contrast, normal vertical gene transfer or inheritance occurs from a mother cell to the daughter cells. If an investigator tracks down an ancestor by looking at the contents of the attic or a genome, they can do a reasonable job if the attic only contains things inherited from your parents, and they from their parents, ad infinitum. But when you have things that are stolen from neighbors, suddenly the task of tracking down ancestors becomes muddied: is your neighbor a relation, an ancestor, unrelated? Strategies that minimize stolen genes in the analysis are critical when looking for LUCA.

Martin’s group was cognizant of the HGT problem and put in place filters to reduce them.

The result was 355 protein families, bundled into 21 functional categories such as ribosome biogenesis, translation, RNA modification, DNA binding, etc.

From the genes that survived the multiple filters in this analysis, Martin’s group could now speculate on what LUCA was like.

A good look at LUCA

A quick word on what LUCA was not… LUCA was the last universal common ancestor of bacteria and archaea, but was not the first cell or bit of life. Just as your parents are the last common ancestor of you and your siblings, your parents are not the first human. But we need to work our way backwards, one step at a time. And LUCA is our first step.

Giant tube worms feed on archaea at a vent in the Galapagos Rift

First of all, the Weiss paper showed that LUCA was only half alive since it appeared to be missing many basic metabolic genes. LUCA depended on geochemistry to provide many critical biochemicals such as amino acids (the raw materials of proteins) and nucleotides (the raw materials of DNA and RNA). These are the basic biochemicals that most organisms have the ability to either synthesize or obtain from their organic foodstuffs. In the immediately previous blog, I discussed the different types of pre-biotic chemistries that might have created an accumulating abundance of amino acids and nucleotides in the primordial soup. LUCA would likely have harvested the necessary organic components from the soup in which it swam.

Second, LUCA was a thermophile, an organism that was adapted for and thrived in the superheated volcanic sea-bottom vents that today we call black smokers or hydrothermal vents. This is based on an enzyme in LUCA called reverse gyrase which is unique to modern organisms called hyperthermophiles (organisms that love very high temperatures). Reverse gyrase protects DNA at high temperatures. Other enzymes in LUCA are consistent with organisms that thrive in hydrothermal vents.

Third, LUCA obtained energy from inorganic compounds and lived without oxygen. The gases hydrogen, carbon dioxide and nitrogen were all LUCA needed to survive (unlike us who need organic compounds we call food and oxygen to survive).

Fourth, LUCA contained a number of ancient enzymes. Biologists have long considered modern proteins that require iron-sulfur (FS) clusters to be relics of ancient enzymes, based on tracing amino acids through a variety of bacteria to eukaryotes. FS clusters are among the most common cofactor (something required for an enzyme’s activity) in LUCA’s proteins.

The response to LUCA…

Science never proceeds along a nice, clean, unobstructed path. In fact, the hair-pulling and shin-kicking amongst researchers seems to be the normal course of scientific dialog. To get a sense of that liveliness, check out the published comments and counter-comments between those objecting to the Weiss paper, and the Martin Lab’s feisty response.

From the objectors:

“To the Editor — We wish to comment on several claims made in the paper by Weiss et al., which describes a genomic analysis that they believe is consistent with the origin of life and emergence of a progenote-like last universal common ancestor (LUCA) in hydrothermal vent conditions….”

Needless to say, the objectors are well known for their hypothesis that life arose in freshwater hot springs. Their objection to a strongly competing hypothesis is natural.

From the Martin Lab came the following:

“Weiss et al. reply — In response to our recent paper, Gogarten and Deamer write in with five paragraphs. They focus on traditional views concerning the nature of the last universal common ancestor (LUCA). We find the current exchange worthwhile in that it highlights several important differences in older and newer concepts concerning both LUCA and approaches to inference of its properties…”

Zing! The objections, say Weiss et al., are from old fogies, while our data and hypothesis is state-of-the-art shiny and new… that is how I interpret that exchange.

A commentary published in support of the Weiss paper is this one here. The author of that commentary is a microbiologist, so he has the requisite expertise to evaluate it properly. His research interest is in the evolutionary origins of the eukaryotes, and as far as I can tell from his publication history, he has no dog in the fight on where life arose (i.e., he is relatively unbiased).

The placement of LUCA as a hydrothermal extremophile, living and loving amid boiling temperatures and toxic heavy metals and gases (toxic to us at least), is a hypothesis requiring significant experimental confirmation. Despite the old-fogy rocking-chair kvetching of the old duuudes Gogarten and Deamer, one comment they made is absolutely spot on:

“…We hope that in the future, the authors will propose feasible experiments that will either support or falsify their conjecture about the origin of life in hydrothermal vents…”

That of course is just how science works. Weiss et al. close their paper with the following comment, that their data favors:

“…theories that posit a single hydrothermal environment rich in H2 and transition metals for LUCA's origin over theories that entail many different kinds of chemical environments catalysing one reaction each.”

The obvious experiment suggested by that comment is also a very hard one, and that is to replicate a hydrothermal environment and demonstrate that a single set of conditions can give rise to a minimal set of complex biochemicals consistent with LUCA’s genome.

Saying goodbye to LUCA…

We have not made tremendous progress in our search for the origin of life by working backwards from current living organisms to LUCA. If the results of this Weiss paper stand the test of time and of challenging experiments, then we have made an important but very small step in time back from the world of bacteria and archaea some 3.5 billion years ago to the common ancestor of both. But we need to move significantly farther back in time and complexity from LUCA and the complex biome in which LUCA likely existed, to approach the origin of life.

We have just met LUCA, but now we need to zoom right on by to attain our objective.

In the previous blog, I mentioned that Francis Crick, Leslie Orgel, and Carl Woese (who we met again in this blog here), proposed that RNA was the original genetic code. Not only that. RNA was probably also one of the first enzymes. And one of the most important enzymatic activities for cells is the translation of RNA into protein. Today, the cellular machine that translates RNA to protein in all living organisms from bacteria to man, is the ribosome, and at the heart of the ribosome is an RNA enzyme. In almost every other case the vast majority of other enzymes are proteins.

Evolution of ribosomes among three domains

The ribosome is a big molecular machine made of both RNA and proteins. It comes in two pre-assembled parts, a small sub-unit and a large sub-unit. The ribosomal proteins play an accessory or regulatory role – and almost none of the ribosomal proteins are required for the ribosome to work. The core functions of a ribosome are two-fold – and done by RNA.

The small sub-unit has a tiny region at its core called the decoding center (DCC), a strip of ribosomal RNA which helps read the messenger RNA carrying the genetic code from the genes in our DNA, the code for how to make a protein. How to make us.

The large sub-unit has at its core a region in its ribosomal RNA called the peptidyl transferase center (PTC) which catalyzes the joining of an amino acid to the growing protein chain. That is the enzymatic heart of the ribosome. And arguably, that is the enzymatic heart of life.

When the small and large sub-units come together, they form a little chamber to accept incoming transfer RNA (tRNA), each of which carries a single amino acid to be added to the growing protein. If the tRNA’s code matches the code on the messenger RNA, the tRNA and its amino acid move on to the next step. The PTC transfers the peptide bond of the amino acid from the incoming tRNA to the growing protein. The subunits also form an exit tunnel which allows the growing protein chain to exit.

RNA molecules form these key functional cores of the ribosome. Proteins, though they stud the outside and thread through the ribosome, never come close to the enzymatic heart of the ribosome.

LUCA may have finalized the ribosome and when it passed on to bacteria and archaea, it has stayed almost exactly the same among those two groups over the past several billion years. In eukaryotes, the ribosome is evolving at an exponential rate.

We may be approaching the informational event horizon for the origin of life, the point behind which all data is lost irretrievably from this direction, from the direction of today looking back to the past. Whether LUCA is a black hole or the infinitesimal spot in time and space from which the Big Bang occurred, either way it is unlikely that the data we have at hand among the living organisms today, can give us any insight into organisms that predated LUCA and back towards the origin of life.

If there is a portal through which we can move back farther than LUCA, it will likely be through the catalytic and decoding RNAs at the heart of the ribosome. But how that portal will be designed and built is not clear now, any more than the design of a time machine is clear to us.

Perhaps the most productive path with be a highly collaborative venture that works to go over or under or around the event horizon, the brick wall blocking our view of the origin of life… a collaboration with active feedback on a given team between biology and the other physical sciences such as geology, astronomy, physics and their hybrids geophysics, astrophysics, etc.

The search goes on…