Hello, and thank you for listening to the MicroBinfeed podcast. Here, we will be
discussing topics in microbial bioinformatics. We hope that we can give you some
insights, tips, and tricks along the way. There is so much information we all
know from working in the field, but nobody writes it down. There is no manual,
and it's assumed you'll pick it up. We hope to fill in a few of these gaps. My
co-hosts are Dr. Nabil Ali Khan and Dr. Andrew Page. I am Dr. Lee Katz. Both
Andrew and Nabil work in the Quadram Institute in Norwich, UK, where they work
on microbes in food and the impact on human health. I work at Centers for
Disease Control and Prevention and am an adjunct member at the University of
Georgia in the U.S. Hello and welcome to the Microbial Bioinformatics podcast.
Nabil and Andrew are your hosts today, and this is our extended holiday special.
What better topic for a fireside chat than bacterial taxonomy? There has been a
lot of discussion about bacterial taxonomy with the recently announced changes
to Phyla, and this has revealed a lot of misconceptions around taxonomy in
general. One of our guests, Professor Mark Palin, approached us to try and weigh
in and set the story straight. Joining him, we have a very exciting and esteemed
panel to discuss this meaty topic. We have Professor Phil Hugenholz, who is
Director of the Australian Center for Ecogenomics at the University of
Queensland. We have Professor Ian Sutcliffe, who is a Professor of Microbiology
at Northumbria University and Chair of the International Committee of
Systematics and Prokaryotes. And Professor Mark Palin, who is a Professor of
Microbial Genomics at the University of East Anglia and Research Group Leader at
the Quadram Institute. So let's start right at the beginning. How did all of
this taxonomy business get started, Mark? Taxonomy started, as we know it now,
with Linnaeus, who was a Swedish doctor and a Swedish naturalist who looked at
nature and could see what he considered a system of nature, a natural system out
there. And he devised a hierarchical system of classification for plants and
animals, where groups fit within groups in a very tidy fashion. And devising
that system of taxonomy was one of his great achievements. The second great
achievement was that he also overlaid over that a system of nomenclature. And he
swept away a lot of the very confusing approaches where people described things
in sentence-long descriptions. And his key achievement was that he came up with
the so-called Linnaean or Latin binomial as a way of describing species, which
we still honour today. So we call humans Homo sapiens and we call bacterium
Escherichia coli. And so this was Linnaeus's great achievement. And we, by and
large, stuck with the approaches that Linnaeus laid out in terms of taxonomy and
nomenclature since then. Linnaeus was actually quite insightful, though. He
didn't just look at superficial things. He realised that you had to look more
deeply. And so he actually realised as he went along, he said, well, you know,
bats are not birds and whales are not fish. He realised that they both belonged
with the mammals. And it wasn't just a single characteristic like, oh, they fly
and they've got wings or they've got fins and they swim in the sea. He was able
to realise and even included humans in his grand taxonomy. In a sense, it's a
great achievement there in laying out a framework. But he also set us a problem
because what was the reason for all this apparent system in nature? And for
Linnaeus, he actually wasn't a modest man. He said, God creates, Linnaeus
classifies. He basically saw himself as, you know, God's right hand man in
actually revealing the creator's hand in nature. But it took another hundred
years or so for a British naturalist, Charles Darwin, to come up with an
explanation for this system of nature. And Darwin obviously came along with the
theory of evolution by natural selection. Within his theory of evolution, he
came up with an explanation for patterns that Linnaeus had seen. He said, these
are not just arbitrary patterns. I mean, if you look up in the night sky, you
can classify stars into constellations, but they don't mean anything. There's no
deeper meaning to them. They're just arbitrary gatherings of stars and so forth.
Darwin said, no, this stuff we're seeing in the classification of nature
actually has some real meaning. The real meaning is lines of common descent. So
Darwin came up with the idea of evolution, the idea that things change, the
biological world changes over time. But he also came up with the idea of a
branching evolution. And he leant heavily upon the simile of a tree and
described the evolution as like a tree. So let me just quote him, because I
always like to quote Darwin. So he said, basically, the affinities of all beings
of the same class are sometimes being represented by a great tree. I believe
this simile largely speaks the truth. As buds give rise by growth to fresh buds,
and these of vigorous branch out and over the top on all sides, many a feeble
branch. So by generation, I believe it has been with the great tree of life,
which fills with its dead and broken branches, the crust of the earth and covers
the surface with ever branching and beautiful ramifications. So this idea that
there's a tree and that things branch out, that that was a great innovation of
Darwin. But Darwin also pointed out, well, actually, what this means is that
classifications have to be genealogical. And so that was his key point. He said
that basically, as we go forward, all true classification is genealogical. What
we'd say now is phylogenetic, all true classification is phylogenetic. But
Darwin was the one that made that clear, that this was the explanation and this
was the goal of biological classification, was to recapitulate those
phylogenies. Darwin got it right, but most of the people following Darwin didn't
quite get it until the middle of the 20th century when a guy called Willi Hennig
came along and said, actually, look, listen to this, that the goal of
classification is to recapitulate the branches on the tree of life. It's not to
sort of work out whether a thing has a particular, reached a certain level of
complexity or has some particularly salient feature. This has been described as
the battle of grade versus clade. So you can't have a thing called fish, can't
have a taxonomic group called fish, because some fish are closer to humans than
they are to other fish. So if you want to use the term fish, Pisces, you have to
include humans and terrestrial vertebrates in that as well. And so that was a
big change, a big sea change in taxonomy in the 20th century. And it's
interesting if you look, Hennig had some big arguments with a guy called Ernst
Meyer, who was one of the godfathers of evolution in the 20th century. But
Hennig won. Basically, all taxonomists now go with Hennig rather than look at
these kind of grades. And then the last person to mention is Woese. So Carl
Woese was the one that brought all this into bacteriology by showing us that we
could look at molecules and we could look at the sequences of genes in
particular. We didn't start with sequences, but he started looking at the RNA
fragments. But then he showed that you could classify bacteria using sequence-
based approaches. And he came up with similar kind of insights. So he said, you
know, if we look at lines of divergence, things like mycoplasmas, they're just
one small branch within the gram-positive group. And the key point was he said
that there was no such thing as prokaryotes, that bacteria and archaea shouldn't
be joined together, they should be separated. That's me just giving you a very
quick whistle-stop introduction. So Mark, I thought that I spent a decade
working on prokaryotes. So what on earth has gone on there? When did it change?
Well, it changed in the sense that when you look at the assumptions of
cladistics, as Willy Hennig said, you draw branches and you look at how the
branches fit together. And it is one of the assumptions of cladistics that you
can't have triangles, you can't just say these three things branch out equally.
You have to draw a line and say these two branched off first. And what we know
is that eukaryotes are closer to archaea than they are to bacteria. So to group
bacteria and archaea together, that goes against the rules of phylogenetic
classification. So I guess you can, I mean, if we're allowed to use fish, then
we're allowed to use prokaryotes. But it's a vernacular term. It's not a
scientifically accurate term. It's not a term that should be used. And I guess
all of us have to draw a line. Are we going to be precise and scientifically
accurate all the time, or are we going to allow ourselves to use vernacular
terms? So in one of our recent papers, we used the term non-human primates to
describe monkeys. So Ian, you're on a committee with the name prokaryotes in it.
So what has gone on there? Well, I guess I think it's largely a historical
artifact. It reflects, I mean, it used to be called the International Committee
for the Systematics of Bacteria, because, of course, if I remember.  i ddod yn
ôl i'r archaea, ac yna, rwy'n meddwl, ar un pwynt ymlaen, pan oedd y
dealltwriaeth o'r ddatblygiad o'r eicharioedd a'i gysylltiad â'r archaea cyn i
hynny oedd yn ddeall ychydig yn dda, roedd, ac rwy'n credu, yw'n dal i fod yn
ddefnyddio y grwpio o dynion sydd ddim yn cael nuclei gyda term unig. Ac felly,
y term procarioedd, dwi'n meddwl, yn ddod yn ôl i'r archaea, felly procarioedd
fel dderbyn benacolaidd, rwy'n credu, yw'n ddod yn ôl i'r archaea, na, rwy'n dal
i'w ysgrifennu, rwy'n treulio amser fel examenol exon yng Nghaerfyrdd, yn gofalu
cwestiynau a oeddant yn gofyn i ddatblygiadurwyr, oherwydd roeddent yn siarad
am, rwy'n gwybod, mechanismau o dynion a rhenni yn ymgyrchu yn procarioedd, a
oeddent yn gofyn am bacteria, ac rwy'n dweud, archaea, gwnaethoch chi ei wneud
yn gwbl iawn o hynny, rwy'n gofyn, dyw hitchiog ym myd credw Colnom yn fy
syniad. felly rwy'n credu ei fod yn Cadarnham, mae yn cyndeithasus i yw
gyfeiriadwyr ac yn ydyw gwlawant mewn llyfr. Mae'r llywfa Bergydd wedi wyned yn
lunio nhw fel archaeae a bacteria ymhelyth na procarioedd sy'n ymgysylltu
ohonwn, rwy'n credu. Well, my old mentor inaugural pace has been the main flag
bearer for getting rid of the word procarioedd, so in deference to him I have
avoided using the term in titles of, and usually abstracts of papers that I
write, but I agree with Ian that sometimes it's a convenient way, so you don't
have to write archaea and bacteria all the time and people know what you mean. I
take Mark's point that if you're using it when you actually mean bacteria, well
that's no good, but if you actually mean bacteria and archaea and you, you know,
it becomes kind of lumpy in conversation to use it all the time to spell it out,
so yeah, that's kind of, I guess, we might as well say that bacteria are plants
then, you know, that's how they used to be classified, so why don't we just
call, only some of them, only some of them, only some of them, no, no, all of
them, originally all bacteria are lumped in as plants, so it's just, I think
we've got to be more precise in our way of thinking as we go forward. Ian, let's
come back to you for another comment on that response to Mark and Phil. I've got
to make one more point, if you're going to use the term prokaryote, people can't
even decide how it's spelt, is it with a c or with a k, you know, just dump the
term. Yeah, I think we have reasonable consensus on a k, but when I'm writing
formally, most of the texts that I write these days, including a letter I'm just
drafting on behalf of the ICSP, refers throughout to archaea and bacteria rather
than to prokaryotes, and it's at the moment, I think, the International
Committee for Systematic Prokaryotes, the ICSP, probably has bigger fish to fry
than worrying about changing the p in its name to a and b. It'll be part of the
Bachelor of History, though, won't it, because the seat code will take over.
Well, one might argue that the bigger misnomer in the name ICSP is that it's not
described as the International Committee on the Systematic of Cultured
Prokaryotes, since, without jumping too far ahead in things that we may end up
discussing, there is a prescription at the heart of the code and nomenclature
that the ICSP oversees, that we can only validly name things that have been
cultured and deposited in culture collections, and that is probably actually a
more existential matter for the ICSP to be considering, and certainly one that
it has considered recently. So, I mean, I guess in terms of sort of sketching
out where we are in terms of what the ICSP does, I've given a number of
presentations on this over the years, and it is interesting that there isn't a
great knowledge of this. I mean, one of the things that I've just mentioned
there is that the ICSP does a number of things, but its primary role, its
driving role, if you like, is to oversee the maintenance and functionality of
the International Code of Nomenclature of Prokaryotes, to use the P word again,
and that is the primary purpose of the ICSP. It does also have some secondary
functions, one of which is that the rules of nomenclature that are bound up in
that code also require the ICSP to have a journal of record, which is the
International Journal of Systematics and Evolutionary Microbiology, and so the
ICSP is responsible for administering the, that journal is published by the
Microbiology Society, it's actually owned by the International Union of
Microbiology Societies, but the ICSP is the sort of third corner of the triangle
that oversees the publication of IJSEM, and those are two major functions,
interrelated functions of the committee. But I think that also illustrates a
point that I think I wanted to make very early. One of the issues with taxonomy,
and I was going to say the cross that taxonomists bear, but I think actually
taxonomists bear two crosses. One is the unfair cross, this conception that
taxonomy is utterly dictated by rules, and that is utterly, utterly false,
because there is protected in the code of nomenclature is freedom of taxonomic
thought. One person can classify things one way. Phil, for example, can classify
Rhodococcus as a single genus in the GTDB. My freedom of taxonomic thought is
that Rhodococcus can actually, should actually be split into several genera. For
example, where there are rules is there are rules relating to nomenclature, and
that is what is wrapped up in the code, the ICNP, that the ICSP looks after. I
mean, the second cross that taxonomists have to bear, and indeed frequently joke
about themselves, many people, including myself, like to start published
articles by quoting a chap called Sam Cowan, who was practicing in the 1950s,
who made a number of good pithy comments about taxonomists being their own worst
enemies by making their sort of discipline area arcane and boring and
essentially stamp collecting, and we do still carry that particular cross, and I
think there taxonomists are probably guilty about not doing enough to to shed
that particular perception of their work. So Ian, how can we modernize it?
Because it seems like taxonomy has trailed genomics and hasn't caught up. So you
mentioned things like having to deposit cultured strains into, you know, special
collections and whatever, which obviously isn't possible for a lot of the
organisms we're finding with metagenomics, and then there's a whole legacy of
anyone being able to deposit anything in NCBI and it magically appearing into
taxonomy as an official species or whatnot. So how can it be modernized? I've
argued in papers published now over quite a considerable period of time, at
least pretty much a decade or so, that the way forward, and indeed I'm not alone
in this, many people believe this, it's just getting it adopted is the hard
part, is that the future of taxonomy is as a genomics discipline. My personal
belief is that any information that you might need to classify an organism is
encoded in its genome, and there's necessary and sufficient information to come
up with a robust classification is present in the genomes of organisms, and I
think the way we can modernize by shedding the, frankly, it's a conservative
tendency that sort of demands a lot of, frankly, trivial and irrelevant sort of
phenotypic testing be done, which in its worst manifestation, and I can speak
from the heart here because I looked up this morning, as editor-in-chief of
Antony von Lernhop between 2009 and 2019, I personally arranged either the peer
review and editing or certainly the final copy editing of more than 800 species
descriptions, and one of the things that I can confirm, bacterial species
descriptions, is that they are mostly appallingly dull, and they are sort of
dull checklists of, you know, trivial phenotypic tests, one of the ones I always
single out, not entirely fairly, is, you know, how important really is it
whether one organism is positive or negative for cysteine or alamidase, you
know, those kind of miniature biochemical tests, and so modernizing require, I
think, shedding that approach to publication of taxonomic papers. We are still
very much with a lot of taxonomists building careers from a one colony is one
species is one paper. It's a sort of assembly line of you pick the colony off
the plate, if it's 16s RNA looks sufficiently different to other known species,
you do this battery of tests, and then you write it up in a six-page paper that
requires an editor, it requires two peer reviewers, and it requires enormous
amount of human energy and effort and time to get that paper published, and the
reality is that most individual species are not that exciting. It's clear, if
you look at what's written down, the rules are actually very few and far
between. There's just a huge corpus of behavior that has sprung up, the way in
which editors and peer reviewers interpret things, but none of that's, there's
no official taxonomy, there's no official approach to taxonomy, and when we were
working on the chicken gut a couple of years ago, we were working with a  Haran
Oran is an expert on bacterial nomenclature. And I said, we've got a lot of
uncultured things we want to name, but we've also got 30 things that are
cultured and we want to name them. And he said, well, all it says in the code is
you've got to provide a description. It doesn't tell you what kind of
description. You just have to provide a, you have to say what the type strain is
and you have to come up with some kind of circumscription. And so I just adopted
a very terse description, which said, you know, it's basically, this is the type
strain and anything else in the species has to fit within an ANI of 95%. And
that went through peer review and it's published. We did have to deposit those
strains to get them validly named. And that process is still ongoing. I mean,
they've been deposited. It's getting the validation of the deposition is taking
time, well over a year after we sent them off to the type culture collections,
we're getting, we're finally going to get there in the end. But I think that
it's clear, if you look at both taxonomy and nomenclature, what passes as
practice are the opinions of peer reviewers and editors. They are not written
down anywhere as rules that have to be followed. And we can take a blowtorch to
this. You know, in a sense, this is like the reformation. A reformation is
needed. We get rid of all that stuff and we go back to the fundamentals. The
code says you have to do this. The code says you've got to describe the thing.
Here's a description. You've got to provide a derivation of the name. Okay. You
know, you just describe the derivation of the name. You don't have to go into
all that arcane Latin and decide whether Petra is a Latin root or a Greek root
or whatever. You just say from classical roots, meaning this and that, you can
do all that. So I think that my view is that we should stop giving time to these
people, these old style people. And if a journal doesn't want to publish a paper
because it's got the wrong peer reviewers and the wrong editor, publish it in
another journal that's more open-minded. Let's just go around the problem. This
problem will be solved as these people retire and the new generation come in
that just say, why do we need to do all that stuff about quillings and all that
nonsense? We don't. It's nonsense. Yeah. I have a paper in IGSE last month
making a lot of those points, it must be said. And I think actually one of the
things I looked up earlier, and I think Mark may be familiar with this, but this
is a title of a paper by a person called Susan Renner, who is a fungal
taxonomist, as it happens. But the title of her paper from 2016, I think is a
really useful answer in a single sentence to the question Andrew asked about how
do we modernize. And Renner's paper is entitled, A Return to Linnaeus's Focus on
Diagnosis, Not Description, The Use of DNA Characters in the Formal Naming of
Species. And for me, that encapsulates in a sentence, with a sub-sentence,
everything we've just talked about, that the genomic DNA is efficient and to
allow the placing of taxa within a classification. And the description that goes
along with naming things can be a very brief diagnosis. Mark mentioned the ones
he used in his chicken microbiome paper. And we are starting to see papers come
through that say, the classification of this or the novelty of this taxon is
demonstrated by phylogenomic analysis, those kinds of statements. And that is,
for me, speaking personally, is the information to accompany the giving of a
name. Yeah, a short while ago, only a few years ago, our clinical colleagues
used to be quite sneering when they said, oh, that's just a genomo species. As
if, you know, oh, there's multiple genomo species of Acinetobacter. We can't
distinguish them in the lab, so it doesn't matter. That's fundamentally to
misunderstanding. Everything is a genomo species. And genomes have triumphed
over, you know, the phonetic classifications belonging to baggage in the dustbin
of history. And it's time to move on. That, you know, basically we're just
making manifest Darwin's dream, Darwin's vision. And those who wish to look at
phenotypes are the kind of people that would have said, well, really, we should
be calling a whale a fish. Come on, it feels right, doesn't it? No, it doesn't
feel right, it's wrong. And we should stop doing it. Genomes are the only
measure that we use. I mean, we have to give Phil a chance to speak. We have to
qualify it's not genomes. It's a subset of the genes within genomes that are
useful for this purpose. And we do have this problem of horizontal gene
transfer. If we imagine that these genomes were lorries, we're not classifying
on the whole lorry. We're not classifying the cargo, we're classifying on the
cab. The thing that, you know, the small amount that is actually classified and
makes a sensible tree of life classification. But nonetheless, that is
fundamentally a boiled down version of the genome. What about you, Phil? What do
you think on all of this? Well, I agree very much with what's being said. I
think it's actually a really exciting time to be in taxonomy. I do believe I
have you on a record and the bill is saying, I have a tweet from you saying
taxonomy is dead, let it die. I use that actually in talks, but I would say very
much the opposite. I would say we really on the cusp of getting the job done
properly. And there are a few growing pains as we've seen from the Twitter storm
in the last couple of days. But I really am looking forward to getting a full
description of the microbial diversity we share the planet with. And I think
we're heading in that direction in a very strong way. I'm very positive about
the whole thing. All right, excellent. I think it's time for a little break.
We'll be back to talk more about the genomics side of things and how that
integrates with this and some of these recent changes to the nomenclature that
people have been discussing. I want to thank our esteemed guests, Professor Ian,
Phil and Mark, and we'll see you in the next part of our holiday special on the
MicroBin V podcast. Thank you so much for listening to us at home. If you like
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