30 December 2020

Corona Update 30 Dec 2020

Today a short update about a tool to visualize the evolution of  SARS-CoV-2.

 

 

 

 

 

 

One of the tools is GISAID. In this tool one can easily produce phylogenetic trees of SARS-CoV-2 genomes. There are 3848 genomes sampled between Dec 2019 and Dec 2020. Many thousands of variants of SARS-CoV-2 are circulating. To simplify the matter, they are grouped in clades. A clade is a genetically well defined lineage that has reached a frequency of 20% globally and has spread globally (see Tutorials: Clade Naming & Definitions). Clade 19A and 19B are sampled in 2019 and 20A, 20B, 20C are sampled in 2020. Below is a radial phylogenetic tree with 5 clades:

Radial Phylogenetic Tree of SARS-COV-2
click on image for full size

I like the radial display with 5 clades because the clades are visually well separated. The direction of time is from the centre outwards to the circumference. The tree starts at 30th December 2019  with the reference genome (Wuhan, China) and ends at December 2020.

One can easily switch from one display type to another. The most common tree type is the Rectangular tree. The reader is encouraged to try out different display options and data selections (left panel). A map and a time lapse animation are also available.

The clades are not geographically restricted. To show this, select 'Color by Region':

SARS-COV-2 Rectangular tree with 6 regions indicated.
Time runs from left to right. click on image for full size.


Remarkable: geographic locations are distributed all over the tree. No clade is restricted to one geographic region. This is unnatural for a species. This means different SARS-CO-2 clades have been transported all over the globe. Species have been transported all over the world even before the popularity of air travel, and even before travel by ship, but the genetic fingerprints of SARS-COV-2 offer us unprecedented opportunities to trace the movements of people carrying the virus from continent to continent.

To be continued.


GISAID (website)

GISAID (wikipedia)

Official hCoV-19 Reference Sequence  (GISAID)

24 December 2020

Corona updates



This blog post gives short corona updates. Developments are going fast. Here I add very short updates (especially on the evolutionary aspects)  instead of writing many long and detailed blog posts. Most recent on top of the page.



28 December

In the previous update I argued that the new British SARS-CoV-2 variant has outcompeted the existing variants because it has higher transmissibility. But does it also make people more sick than the standard virus? In other words: does it have a higher virulence? The general idea is that there is a trade-off between virulence and transmissibility. If a virus makes you so sick that you stay at home, than the chances of transmission to other people diminish strongly. If you die, the virus is unable to spread to other people. That virus will not cause a pandemic.  On the other hand, if a virus does not make many copies of itself and transmits them to other hosts, the virus will disappear. Making many copies is a burden for the host. To be honest: the host is making those copies! That's why it is a burden. That's why a virus is the ultimate parasite. 

I am not saying that the virus has a strategy. The success of a virus depends on its genetic make-up and how people behave. It is a matter of causes and consequences. However, we could describe the behaviour of a virus as an evolutionary strategy. A successful evolutionary strategy produces the most offspring.

The evolutionary strategy of SARS-CoV-2 appears to be a mix of  virulence and transmissibility. Transmissibility means producing and shedding a lot of copies of itself before the persons begin feeling sick. This is called pre-symptomatic transmission. These persons unknowingly and unintentionally transmit virus particles. Research suggests that up to 45% of infected people are symptom-free transmitters. In younger people transmissibility seems to be maximized.

The second part of the mixed strategy is producing a very high number of virus particles in a subgroup of people, for example in older people. The downside is that these people will get very sick and die. Virulence is high. This is a short term strategy. It is a dead end. Maybe it is better to consider this a side effect of the successful high transmission strategy. In the end, the effect is that SARS-CoV-2 kills people and at the same time spreads around the globe. It resulted in a pandemic. At least, that is the situation in this phase of its evolution. Two facts will determine the long-term evolutionary success of SARS-CoV-2: new mutations and our behaviour.

How the coronavirus escapes an evolutionary trade-off that helps keep other pathogens in check.



25 december

Britse epidemiologen hebben een analyse gemaakt van de nieuwe B.1.1.7 virus variant. Resultaten: van de 17 mutaties hebben 3 een potentieel biologische effect: N501Y, P681H en del69-70. De andere 14 zijn of neutraal of nog onbekend. De eerste twee mutaties zijn aminozuur wijzigingen en de derde is een deletie van aminozuren 69 en 70 van het Spike eiwit. Die ontbreken dus. Uit in vitro experimenten is gebleken dat deze deletie de infectiviteit vergroot. Opvallend effect van de deletie is dat sommige standaard commericiële PCR testen een False Negative geven: ze detecteren de Britse variant niet. Dat is natuurlijk problematisch. Die PCR testen moeten zo spoedig mogelijk vervangen worden door testen die de nieuwe variant wel detecteren.
De epidemiologen concluderen dat de sterke toename van de nieuwe variant niet toegeschreven kan worden aan veranderende sociale interacties of mobiliteit. De variant is dus gestegen in frequentie door het selectief voordeel van de mutaties. Positieve selectie dus. Exacter: differentiële reproductie van genetische varianten in de virus populatie gebaseerd op een fenotypisch effect. Tevens is hiermee aangetoond dat een deletie niet altijd schadelijk hoeft te zijn, maar selectief voordeel kan hebben.

Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England



19 december 

Een Engels team van wetenschappers maakte de vondst bekend van een nieuwe Sars-CoV-2 variant B.1.1.7 die zeer waarschijnlijk in Engeland ontstaan is. Het bijzondere is dat hij verschilt van de bestaande varianten door de unieke combinatie van 17 mutaties die kennelijk in 1 keer ontstaan zijn. En dat is uniek in de korte geschiedenis van het virus. De specifieke combinatie van mutaties is niet eerder waar genomen. Tot nu toe zijn er geen evolutionaire voorlopers gevonden. Wat het meest de pers heeft gehaald is het feit dat de mutant een sterke toename vertoont onder de nieuwe gevallen. Op 9 december had de variant in London al een frequentie bereikt van 60%. De variant is sterk geassocieerd met nieuwe gevallen in Engeland. De politiek heeft hier snel op gereageerd. 

Wetenschappers verschillen van mening over de vraag of die sterke toename door toeval (superspreader event) of door selectief voordeel verklaard moet worden. Feit is dat de variant andere varianten verdringt. Een argument voor de hypothese dat deze variant een selectief voordeel heeft is het feit dat het virus onderdeel dat voor aanhechting aan de menselijke cel zorgt (Spike) maar liefst 8 mutaties heeft. En dat blijkt bepaald niet nadelig voor de verspreiding van het virus te zijn. Dat de variant selectief voordeel heeft kan bevestigd worden door deze te kweken op menselijke cellen in het laboratorium met als controle de standaard corona stam.

Dit is de originele publicatie van de groep die de variant ontdekt en beschreven heeft:

Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations

 

21 December 2020

SONY 90mm macro lens and SONY A6400 camera: amazing performance with available light and image stabilization

12 Oct 2020 Episyrphus balteatus. marmalade hoverfly.
f/7.1. 1/1250 sec. ISO 10.000 [GK_04342.JPG]


When I bought the SONY 90 mm macro lens, the man in the camera shop looked at me and said: buying a macro lens in October?! The autumn is a good time for mushroom photography! I bought the lens at that moment because it has been out of stock for months.

Well, yes, there are a lot of mushroom in October, but there are also insects flying and crawling. See for example the tiny fly above photographed on 12 October.

Pieris brassicae (detail) 14 Oct.
f/10.0 1/8000 sec. ISO 10.000 [GK_4469]

Two days later I detected this caterpillar of the cabbage butterfly on a cabbage.

dragonfly detail 700x700 pixels. 3 Nov 2020
f/4.5. 1/1000 sec ISO 800. [GK_04813]
Sympetrum striolatum (?) (Bruinrode heidelibel)

On 3 November there was a dragonfly sitting on a bench in the park! I am not sure what species it is, it could be a Common darter male. This is certainly late in the year to observe a dragonfly. The picture shows the attachment of the 4 wings to the body. Impressive piece of engineering!

3 Nov. Citroenvlinder
Gonepteryx rhamni
Common brimstone
f/2.8. 1/4000 sec. ISO 400.

Also on 3 November a butterfly sunbathing! One of the last butterflies of this year? I could not come close enough for a good macro.


7 Nov 2020 Episyrphus balteatus.
Dutch: snorzweefvlieg,
Englisch: marmalade hoverfly
original: 6000x4000; this detail: 1000x800 pixels.


On 7 November this tiny hoverfly (above) was resting on Hedera helix in our garden just long enough to take a picture. Temperature: 14°C.!


Suillia spec. (7 Nov.) resting on mushroom
f/7.1. 1/400 sec.  ISO 8000. 2239x1661 pixels

This is a fly of the species-rich Suillia genus, which contains 130 species. They are very difficult to identify without a microscope, but are beautiful.

9 Nov: Neomyia cornicina (?) (O=99.9%) [GK_04920A]
 

9 Nov: Neomyia cornicina (?)
f/7.1. 1/4000 sec. ISO 4000. [GK_04922A]

The next day I spotted a marmalade hoverfly warming up in the sun. A perfect situation for macro:

10 Nov: Episyrphus balteatus (detail)
D: Snorzweefvlieg. E: marmalade hoverfly. [GK_04947]
f/8.0. 1/500 sec. ISO 1000

All pictures are freehand with the SONY A6400 and SONY FE 90 mm F2.8 Macro G OSS lens with autofocus and image stabilization enabled. Original size of pictures: 6000x4000 pixels. The light sensitivity settings varied between ISO 800 and 10.000 and shutter speed settings between 1/500 and 1/4000 sec. Click on images to view full size.

It's amazing that freehand photography with this lens delivers such detailed and sharp macro pictures! It seems, this macro lens is designed for freehand photography. I am really happy with the results. 

Still sharper details should be possible with lower ISO values and a tripod and/or artificial light, but I did not yet try this.

So: October and November are certainly not lost months for macro photography: several fly species, a butterfly, a dragonfly and a
caterpillar. Relevant info: I am located in The Netherlands.

If you have any comments or questions, please use the comments field below.

 

PS: I planned to publish this post a month earlier. But I decided to give priority to the new book of Paul Nurse!

02 December 2020

Nobelprize winner Paul Nurse: viruses are alive! and dead!

Paul Nurse 2019 lecture The Royal Institution

Sir Paul Nurse received The Nobel Prize in Physiology or Medicine 2001 for his discoveries of key regulators of the cell cycle together with Leland Hartwell and Tim Hunt. According to the Nobel committee: 

"From the beginning organisms evolve from one cell, which divides and becomes new cells that in turn divide. Eventually different types of cells are formed with different roles. For an organism to function and develop normally, cell division has to occur at a suitable pace. Paul Nurse has helped to show how the cell cycle is controlled. Through studies of yeast in the mid-1970s, he was able to show that a special gene [cdc2] plays a decisive role in several of the cell cycle's phases. In 1987 he identified a corresponding human gene [CDK1]." (Nobel prize organization)

 

Paul Nurse (2020) What is life?
Paul Nurse (2020)
What is life?

In 2020 Paul Nurse published What is Life? [1]. In the first chapters he explains biology for non-biologists: the cell, the gene, evolution, biochemistry, DNA, and control mechanisms in the cell. Almost casually Nurse tells about his discovery that led to the Nobel prize some 20 years later. These chapters constitute the foundation for the final chapter in which he develops a definition of life.  In the last chapter he defines life with 3 principles. Any entity which operates according to those three principles can be deemed to be alive.

  1. The ability to evolve through natural selection. To evolve, living organisms must reproduce, they must have a hereditary system, and that hereditary system must exhibit variability. Any entity that has these features can and will evolve.
  2. life forms are bounded, physical entities.
  3. living entities are chemical, physical and informational machines. They construct their own metabolism and use it to maintain themselves, grow and reproduce. These living machines are co-ordinated and regulated by managing information, with the effect that living entities operate as purposeful wholes. 

Whenever I encounter proposals for the definition for life, I can't help comparing them with the definition of life of the Hungarian theoretical biologist and biochemist Tibor Gánti. Years ago Gánti proposed a definition of life that stood the test of time. I refer to my description of Gánti's defitinition of life on my WDW website [2]. Reading and listening to Nurse made me thinking again about the definition of life.

The first principle, the ability to evolve, Nurse adopted from Nobelprizewinning geneticist Hermann Muller. According to Gánti evolvability belongs to the Potential life criteria. That means evolvability is not a necessary property of an entity to be alive. But Nurse does not make the distinction between actual (absolute) and potential life criteria. There are a few practical problems with his first principle. According to evolutionary biologist Szathmáry evolution is not a property of an individual, but of a population. Also, variability is not a property of an individual, but of a population. The principle also causes difficulties when applied to a somatic body cell of an animal or plant. All somatic body cells will eventually die when the organism dies, and they leave no descendants in the next generation. Nobody would deny that somatic cells are living. But at the same time one cannot say that somatic cells in your body have the evolvability property. Only germline cells are involved in reproduction. On the level of an animal there can be also a problem. Mules are infertile, so no reproduction and no evolvability, but they are alive. Finally one comment about evolvability. Nurse's first principle suggests that the only function of the hereditary subsystem is evolvability. Nurse does not state explicitly that the informational subsystem "is useful for the whole" (Gánti's 4th absolute life criterion) and controls metabolism.

His second principle is:'life forms are bounded, physical entities'. This equals Gánti's Chemical boundary system. What is the boundary? Unfortunately, the concept boundary is used in an ambiguous way. For cells the boundary is the cell membrane (animals) or cell wall (plants). But viruses have a capsid which is clearly distinct from the semi-permeable membrane of a cell. A capsid does not have the functions a cell membrane has. This has consequences.

His third principle is complex. It is almost a complete definition of life because two of the three Gánti subsystems are included: a Chemical information system (for example DNA) and a Chemical motor system (metabolism). Nurse also included growth and reproduction in his third principle. According to Gánti growth and reproduction are Potential life criteria. Adults don't grow, and a non-dividing cell –for example a neuron– is not dead. That's why growth and reproduction are not necessary for being alive. They are a potential characteristic of life. The properties 'co-ordinated and regulated' and 'maintain themselves' equal Gánti's third Absolute criterion: "A living system must be inherently stable".
 

Are viruses alive? We all agree that bacteria, plants and animals are alive. Paul Nurse says viruses are alive too [7]. I disagree. The most important reason I think why viruses are not alive is that viruses are not cells and they never become cells. Not being a cell means not having a semi-permeable membrane which enables transport of molecules in and out of the cell. Viruses are a sort of stripped-down cells. Stripped down to the bare essentials: RNA or DNA with a protein coat.

Although Nurse's principles include an abstract 'boundary', in his talk he said: "the cell is the basic structural and functional unit of life" [3]. That is Robert Hooke's cell theory. Nurse is serious about the cell theory. Rightly so. In the first chapter The Cell: Biology's Atom he writes:

"What I mean by this is that cells are the smallest entities that have the core characteristic of life. (...) The cell is the simplest thing that can be said, definitely, to be alive" [5]. 

Since viruses are not cells, viruses cannot be alive. Viruses are dead RNA or DNA molecules!

In response to a question from the public Nurse says "viruses are dead outside the cell and alive inside a cell" [7]. This is an unsatisfying compromise. It reflects the fact that viruses outside a cell are chemically inert; they cannot defend themselves against outside disturbances and degradation by physical forces (UV light, heat,etc). They have no metabolism. They are passive entities subjected to physical forces. But in a cell they are active and replicate according to Nurse. But this is not correct, because the cell does all the work of replicating and so on. The virus DNA or RNA does not and cannot replicate itself. But if Nurse wants to claim that a replicating virus (which is just a piece of RNA or DNA) is alive, than a chromosome or nucleus or mitochondrion must be alive too? [8]. The property 'being alive' belongs to a higher level than molecular level. It is a property at the level of the cell. 

 

A stripped down car?


A car is a vehicle on wheels, with an engine, steering wheel, gas pedal, brakes, fuel tank, seats, etc. that moves autonomously. If we strip the car of everything except the wheels, what do we get? Is it a stripped-down car or a trailer? The trailer is connected to a car and has wheels and it moves when attached to the car. It does not move when not attached to a car. A car can move without a trailer, but a trailer cannot move without a car. Importantly, when the trailer moves, it does not suddenly become a car. Does it make sense to point to the fact that cars also depend on external factors (fuel)? So, there would be a continuum from car to trailer? No. But, cars and trailers share the property 'having wheels'. They are objects with wheels. That is the only common property.


Virus: a stripped down cell?

Similarly, do we call viruses alive just because they can be viewed as stripped down versions of a cell? [6]. No. But there is one thing both have in common: DNA or RNA. Even more importantly, they use the same genetic code (the code that translates DNA sequences in to protein sequences) as all life. They need to have the same code, because otherwise their genes would be gibberish for the cell and they won't be able to replicate and produce new virus particles. Furthermore, viruses adapt to their hosts. For example the SARS-CoV-19 is perfectly adapted to the human ACE2 receptor. A perfect match. There is no doubt viruses are evolving entities. But one has to distinguish between evolving entities and living entities:

Viruses are evolving but not alive.
James Griesemer & Eörs Szathmáry [2].

When accepting the view that viruses are maximally stripped-down versions of cells, could we conclude from that that RNA or DNA are the bare essentials of evolution? The virus is a set of selfish genes. There you have it: the common property of cells and viruses is: replicating RNA or DNA. The classes of viruses and cells do not overlap, but are included in a higher class of objects with replicating RNA or DNA. Is this a rediscovery of the essence of Darwinism? I think so. It's all about replicating entities! Replicating entities that make errors and evolve. The 'units of life' are cellular. The 'units of evolution' are strings of DNA or RNA. 

 

Conclusion

Nurse is absolutely right that the cell is the simplest unit that can be said to be alive. We now understand why the cell is the smallest life form: only a cell can integrate the three necessary components of life: a semi-permeable boundary, a hereditary information system and a metabolism. A logical consequence is that a virus cannot be said to be alive, neither inside nor outside a cell. I disagree that this is an arbitrary decision. It just follows from the cell theory. 

Furthermore, Nurse is absolutely right about the profound interconnectedness of all life. And, I fully agree, viruses are intimately and necessary connected to life. They speak -so to say- the same language. But that does not make them living. 

I also fully agree with Nurse that the ability to evolve is important. There would not be a single human on this planet without evolvability. But evolvability is a property of populations of DNA/RNA based units.

I thank Paul Nurse for writing such a stimulating book!


 

Update 13 Dec 2020: small edit and note 8 added.


Notes

  1. Paul Nurse (2020) What is Life. Understand Biology In Five Steps, David Fickling Books. It is a popular science book without footnotes, index, and literature list. -I don't know whether the hardback is illustrated, but my e-book is not. Here is a short interview with Paul Nurse about the book. I could not contact the publisher via the contact form on their website, there isn't any confirmation that the message have been send successfully (only a blanc screen!);  and the email address info@davidficklingbooks.com does not exist (mailer-daemon: "we were unable to deliver your message").
  2. The Principles of Life. superior insights into the nature of life is about Tibor Ganti's definition of life on my WDW website.
  3. What is Life? Sir Paul Nurse - 2020 James Martin Memorial Lecture youtube 6 Mar 2020. Please note that being a cell is not included in his three principles.
  4. Biography of Paul Nurse at Nobel website. Contains many interesting details about his life. Recommended. Not in the book.
  5. Paul Nurse: "What I mean by this is that cells are the smallest entities that have the core characteristic of life. This is the basis of what biologists call cell theory: to the best of our knowledge, everything that is alive on the planet is either a cell or made from a collection of cells. The cell is the simplest thing that can be said, definitely, to be alive". (22/360 e-book)
  6. Stripped-down cell: everything is removed from the cell: all proteins, amino acids, ATP, water, cytoplasm, mitochondria, ribosomes, nucleus envelope, etc.
  7. In the book he wrote: "You could almost say that viruses cycle between being alive, when chemically active an reproducing in hosts cells, and not being alive, when existing as chemically inert viruses outside a cell." 328/360. He adds: almost all other forms of life are also dependent on other living beings. Added: 11 Dec 2020
  8. Mitochondria are an interesting test case for the definition of life. They have semi-permeable membranes, have metabolism, produce energy and have DNA. That should suffice for being alive. They cannot exist independently outside a cell. But almost all other forms of life are also dependent on other living beings according to Nurse. Just as a virus and other obligate intracellular parasites. Added: 13 Dec 2020

 

See also:

Paul Nurse: The Royal Institution 2019 lecture What is Life? (youtube)