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Wednesday, September 09, 2015

Major advances in genome biology

I recently stumbled on a paper with an intriguing title" "Sixty years of genome biology" (Doolittle et al., 2013). It celebrates the 60th anniversary of the Watson & Crick paper on the structure of DNA. The editors of Genome Biology describe key advances in genome biology.


Several editors (Graveley, Ule, Henikoff, Doolittle) said that the discovery of "genes in pieces" was a very significant advance in genome biology in the past sixty years. You can't argue with that.

Restriction Mapping

George Weinstock counts restriction mapping as a key advance. I understand his point since the development of restriction mapping gave us maps of the actual structure of the genome for the first time (genetic maps are imprecise and depend on the presence of mutations).

A new regulatory paradigm: micoRNA

John Rinn, who coincidentally works on small RNAs thinks this is a significant advance in genomics. I don't agree.

The original 'data explosion': microarrays

Alicia Oshlack is an astrophysicist who got into genomics through bioinformatics and the analysis of microarray data. Microarrays are important in genomics and should be included in any list of significant advances as long as the list includes technological advances.

Unlocking 'genetic messages': sequencing technologies

Michael Schatz says, "The most significant advance in genome biology since 25 April 1953 has been the rise of large-scale DNA sequencing ...." He is correct, if technologies are to be included in the list.

'Sequence is power': the human and mouse genome projects

Chris Ponting, Mark Gerstein, and Peter Fraser think that the publication of the human genome sequence is the most significant advance in genome biology. I suppose it depends on what you want to know about genomes. If your focus is on humans and medicine then, obviously, the sequence of the human genome is important. I thought the sequences of the yeast, nematode, and Drosophila genomes were pretty exciting and so were the sequences of bacterial genomes.

Retelling the human story: analysis of ancient and historical DNA

The is Detlef Weigel's contribution.

The exception to the rule: lateral gene transfer

Curtis Huttenhower thinks that the discovery of lateral gene transfer is "one of the most remarkable [discoveries] in the history of genome biology."

Nobody mentioned junk DNA and the resolution of the C-value paradox. Nobody mentioned the small number of genes in the human genome in spite of the fact that a great many articles begin with the claim that this was a shocking discovery [but see False History and the Number of Genes]. Jernej Ule mentioned alternative splicing but nobody else did in spite of the fact that many papers claim that most human genes are capable of making several different proteins. This is also a false claim, IMHO, but you'd never know that from reading the journal. Peter Fraser was the only one who mentioned the vast regulatory network of enhancers as claimed by the ENCODE Consortium. If true, that would clearly count as a major discovery. (It's not true.) Eukaryotic genomes are chock full of defective transposons but none of the editors thought that was a key advance in our understanding of the genome.

Doolittle, W.F., Fraser, P., Gerstein, M.B., Graveley, B.R., Henikoff, S., Huttenhower, C., Oshlack, A., Ponting, C.P., Rinn, J.L., Schatz, M., Ule, J., Weigel, D., and Weinstock, G.M. (2013) Sixty years of genome biology. Genome Biol, 14(4), 113. [doi: 10.1186/gb-2013-14-4-113]


Jonathan Badger said...

I'm also annoyed at some of the hype regarding micro-RNAs, but do you not seriously consider Victor Ambros' discovery of lin-4 a major discovery? He and Gary Ruvkin (who explained more of the mechanism of it) got the Lasker for it, and that kind of means they are on the short list for getting a Nobel one of these years.

Joe Felsenstein said...

"Retelling the human story" through DNA is major and interesting, but I am not sure it was surprising. Back in the 1960s Luca Cavalli-Sforza starting arguing for studying human prehistory by studies of present-day molecules (at that time by blood-groups and electrophoretic mobility of proteins, but using DNA sequences, once those were available).

Svante Pääbo developed the use of ancient DNA, by being careful about contamination. (There was an embarrassing period in the mid-1980s when everybody was finding dinosaur DNA, which just happened to have the same sequence as the nearest lab technician).

These are major applications of DNA, but are they major "discoveries"? I would say that starting with Cavalli-Sforza, it was realized that this information was out there -- it just needed to be obtained. So not discoveries, really. But the title of the Doolittle et al. paper says instead "advances". And I guess that these are advances, if not discoveries.

Ed said...

My vote for one of the major advances from a technical point of view is PCR. There's a lot of stuff we couldn't have done without PCR, like microarrays.
A former lab colleague of mine used to reminisce about 'the days' when he needed to add new DNA polymerase after each step because they didn't have Taq polymerase then...

Piotr Gąsiorowski said...

I wish they'd put more emphasis on the second part of the section title (Analysis of ancient and historical DNA). Humans are cool (at least to other humans), but we have been able to "retell" the stories of lots of other species: dogs, cattle, horses, pigs, bears, lice, maize, etc., etc.

Jonathan Badger said...

@Joe Felsenstein
The contamination issue is just a coverup for the fact that the technicians are secret dinosaur-people and Svante Pääbo himself is the Mummy.

Bill Cole said...

Although it is early in the game, I think CRISPR technology and its potential uses discovered at UC Berkeley is a candidate for the list.

whimple said...

Or more broadly you could say synthetic genomic biology is a major advance (in the making).

Joe Felsenstein said...

Yes, we're a bit biased that way, being humans ourselves. On the other hand, humans, having culture, have fairly large and complex amounts of history.

Piotr Gąsiorowski said...

Very true. But you can also learn something about human history by analysing the DNA of ancient and historical lice (for everywhere that humans went their lice were sure to go):

Lice from Napoleon's soldiers
Pre-Columbian lice from Peruvian mummies
Ancient nits

Robert Byers said...

Its cool about the genome understanding progress . Although discoveries about it are like columbus discovering the new world. Its there to be discovered.

As a creationist i would stress that any history from genes would only be accurate if it was settled there is no way for other mechanisms to change genes. I think there must be and so its a waste of time seeking history from genes.
I think a new word should be invented. Comparative genetics as opposed to genetics alone when striving to draw historical relationships from genes. Its all just presumptions that one can extrapolate backwards based on no chance of interference in genetic makeup.
hopefully iit all leads to medical discoveries to heal us.

The Lorax said...

"any history from genes would only be accurate if it was settled there is no way for other mechanisms to change genes"
1. Ok, is there another mechanism? and 2. what is the evidence for this mechanism?
"I think there must be"
So the answer to question 1 is No.
"its a waste of time seeking history from genes."
and the answer to 2 is that the answer to 1 is No because there is no evidence.

Bill Cole said...


Claudiu Bandea said...

Interestingly, the fist 3 major advances in genome biology, introns, restriction enzymes, and microRNAs, evolved as defensive mechanisms against viral invasions, just like the symbiotic DNA, usually referred to as "junk DNA" (, which to Larry's disappointment and mine did not make the list.

Claudiu Bandea said...

And, I forgot to mention that the hottest development in genome biology is genome editing using the CRISPR/Cas system, which evolved as an antiviral adaptive defense system, just like the symbiotic DNA, formerly known as "junk DNA".

Apparently, most of the genome as well as the nucleus and the cellular domains have evolved as anti-viral defense systems, which is not surprising considering the prevalence of viruses and their peculiar life cycle.

Robert Byers said...

Huh? my point stands. Are other options for mechanisms dismissed out of hand and so only comparative genetics is the road to truth.
Yes there are other mechanisms or i think so.
I don't need to provide evidence but show they are excluding other options and so conclusions are not scientific ones.

SRM said...

Are other options for mechanisms dismissed out of hand and so only comparative genetics is the road to truth.

Yes Robert, the idea that there are minature leprechauns in every cell that are re-arranging nucleotides about according to need has also been dismissed out of hand. This is deeply vexing to the molecular leprechaunologist community.

Do you understand my analogy. You are beholden to your convictions, and that is your right.But personal convictions, regardless of how strongly and sincerely they are held, do not trump empirically deduced facts. In fact they are poison to any attempt to truly understand the nature of things. Because you are beholden to literalist interpretations of human interpretations of ancient human writings, you are missing out on a more factual understanding of the acts of the god you believe in.

SRM said...

I haven't read the piece on genomic sequencing, but surely the first whole genome sequencing of prokaryotes (and viral genomes) ought to have a prominent role in history. I am certainly biased, but it is remarkable the extent to which prokaryotic biology is ignored by many people, given that from several perspectives they are the alpha and omega (so to speak) of all life on earth.

SPARC said...

What impressed me most during the last 20 years is the degree of sequence and gene structure conservation as well as how much synteny we observe even between only distantly related species. Thus, I would count wet lab methods and algorithms developed to compare genomic sequences and complete genomes as mjor advances in genome biology.

Petrushka said...

Perhaps a bit off topic, but in the realm of technical advances one shouldn't lose track of advances in computer technology and programming tools. In particular, the price of computers capable of manipulating large databases has plummeted,

Robert Byers said...

nothing to do with me.
Its the evolution side which too quickly concluded there is only one option for genetic likeness. only one mechanism.
Comparative genetics is wrong in drawing genetic trails. i'm saying at least it should be seen as a error in only seeing one option. too quick settling things.

peer said...


These mechanism not only exist (not evolved) as defense mechanisms, but also as variation-inducing mechanisms.

Symbiotic DNA (currently non-coding DNA) may function as a treasure trove for novel genes, frontloaded sequences with potential functions that can become functional in the appropriate genetic context (for instance through positioning of tranposons, ALUs, and other tranposable and transposed elements (TEs) containing promoters and enhancers.

Frontlaoding explains most, if not all, observations on genomics. Frontloading is the new paradigm.

peer said...

"(There was an embarrassing period in the mid-1980s when everybody was finding dinosaur DNA, which just happened to have the same sequence as the nearest lab technician)."

Only if the nearest lab technician was a turkey...

peer said...

The minature leprechauns of SRM are nowadays referred to as proteins, lncRNA, etcetera.

Nothing in biology proceeds without such nanomachines. Not even mutations.

Further, there is now plenty of evidence for genes without evolutionary history. In particular microRNA and lncRNA genes. But also many protein coding genes are orphans.

So, I agree with Robert Byers.

Joe Felsenstein said...

No, there were cases where the sequenced dinaosaur DNA turned out to be "mammalian".

peer said...

So, how do you know it should look like...? You have never seen a DNA sequence of a sdinosaur, do you?

I remember an article where dinosaurs proteins cross-reacted with antibodies raised agains turkey proteins...

Mikkel Rumraket Rasmussen said...

That's because turkeys are dinosaurs, and proteins aren't DNA. There has still not been any sequenced DNA found in any dinosaur that turned out to be dinosaurian. It's usually mammalian(often human, or lagomorph).

The Other Jim said...

No, but we have see human sequences, and they ended up being the same as the purported "dinosaur" sequence, so...

DK said...

WTF is "synthetic genomic biology"? Sounds like meaningless random sound.

CRISPR is just an easier way of doing what was already doable. Unless the efficiency and fidelity are improved dramatically, CRISPR will not result in revolutionary advances. And it's too early to tell if the radical improvement is even possible.