
How Many Genes Do Cells Need? Maybe Almost All of Them - digital55
https://www.quantamagazine.org/how-many-genes-do-cells-need-maybe-almost-all-of-them-20180419/
======
mxwsn
This line of thinking really highlights how building models that predict
phenotype from genotype assuming linear and independent genetic contributions,
though useful for predicting something like height [0] [1], is not going to
generalize sufficiently to solve the lofty goal of personalized precision
medicine even with an explosion in data.

Biologically, we know tons and tons about the interconnected biochemical
pathways that _cause_ a lot of activity in the cell. It's impressive that
statistical modeling approaches that ignore this knowledge earned by thousands
of humanyears worth of work can work so well in some domains, but I'm wary of
the possibility of academic communities isolating themselves from empiricism
and continuing to make mathematically-convenient assumptions, which in the
long-run helps no one but themselves.

[0]
[https://news.ycombinator.com/item?id=16392877](https://news.ycombinator.com/item?id=16392877)
[1]
[https://www.biorxiv.org/content/early/2017/09/19/190124](https://www.biorxiv.org/content/early/2017/09/19/190124)

~~~
carbocation
I don't think this is ignored by the scientific community at all. For example,
Eric Lander's group has a pretty nice treatment of why additive models can't
explain heritability [1]. And this is coming from the same Eric Lander who has
done some of the key work in complex disease / additive genetic modeling.

Imagine you're in a world where you are handed down some knowledge there are
Newtonian models, and more advanced models that use relativity, but you don't
know what the constants are yet. We're still looking for the Newtonian
constants. We know there is much more out there once we understand the basics.
But the basics are still worth understanding.

1 =
[http://www.pnas.org/content/109/4/1193](http://www.pnas.org/content/109/4/1193)

------
derefr
Hypothesis: it’s not so much the _content_ of the genes that’s brittle, as
that there are very few proteins as “smart” in how they walk the genome as
CRISPR is (and even it’s no Einstein.)

There are likely cellular genetic repair mechanisms—especially in “small”
genebases that don’t use fancy tricks like methylation/acetylation—which
“hardcode” assumptions about gene number, gene size, positions of important
proteins, etc.

Just because DNA itself is a robust data-structure (with features like start-
stop tags, commented sections, etc.) doesn’t mean that all the algorithms
(proteins) that have evolved to utilize that data-structure query or mutate it
in equally-robust ways.

Imagine a codebase started off by a brilliant and strict engineer... and then
followed on by a million forks-of-forks-of-forks, all done by average Joes
just “scratching their own itch.” That’s the type of software encoded in 99%
of the DNA on Earth. The codebases where “every line counts” and has been
carefully selected for are far fewer—mitochondria, certainly, but i hesitate
to name any other clear candidate.

~~~
vanderZwan
> _Imagine a codebase started off by a brilliant and strict engineer... and
> then followed on by a million forks-of-forks-of-forks, all done by average
> Joes just “scratching their own itch.”_

I would be careful with that example, before you start to sound suspiciously
creationist. At least, the Christians I know that deny evolution tend claim
everything was created perfectly and since has only slowly degenerated over
time.

~~~
cwbrandsma
As you meet more Christians you will find more variation in what they believe.
All should consider themselves "Creationist", but there are MANY competing
ideas, from Ken Ham "5000 years old or bust", to Catholic "could be billions
of years", and a lot of version in between. For instance, a friend of mine is
a biology professor at the local university, his PHD is in fish evolution, and
is a very conservative Christian.

~~~
Canadauni
Francis Collins is a well documented example of a Christian who very much
contrasts Ken Ham as the current head of the NIH and director of the Human
Genome Project.
[https://en.wikipedia.org/wiki/Francis_Collins](https://en.wikipedia.org/wiki/Francis_Collins)

~~~
jhawk28
It comes down to what you hold to be true. If you believe Genesis is
historical fact, then the interpretation of the science facts are wrong. If
you believe the Bible is true and that the interpretation of science facts are
true, then you see Genesis in a figurative interpretation. If you reject the
Bible, then you will see the narrative of the Bible as false and the
scientific interpretation as true.

------
dddddaviddddd
In bacteria at least it's well-established that natural selection favours a
smaller genome -- hence why antibiotic resistance will be dropped if the
selective pressure is removed.

~~~
danieltillett
Unfortunately, it is not dropped completely, just reduced in the bacterial
population. It would seem a simple idea to just rotate antibiotics (use for a
few years then put on the shelf for a few years), but once a bacterial
pathogen acquires resistance it never really loses it and once you start using
the the antibiotic again the resistance roars back very quickly.

------
callesgg
What definition of gene are they using is this article?

~~~
IAmEveryone
The same as everyone, I. e. a protein-coding segment of DNA?

~~~
callesgg
No that is not true, there are genes that does not contain protin coding
segments.

There is no clear definition where a gene starts and ends. Some define it as a
segment that codes for a specific feature but that is a recursive definition.

Here is an article about what I mean:

[https://www.gmwatch.org/en/news/archive/2000/8975-genetic-
de...](https://www.gmwatch.org/en/news/archive/2000/8975-genetic-determinism-
is-dead-theres-no-such-thing-as-a-gene-27122000)

