No human genome has ever been completely sequenced • Hacker News Board

Re: No human genome has ever been completely sequenced

#31

Post by Bartweiss » Mon, Oct 23, 2017, 6:14 PM UTC

> * A gene called ARHGAP11B, which was created by one such duplication, causes the cortex to develop the myriad folds that support complex thought; SRGAP2C, also a duplication, triggers brain development.*

A question I've never seen addressed: is one justification for junk DNA to create space for beneficial mutations?

Obviously some mutations are actively harmful, but the reason most mutations are destructive is that they break something already-useful into something inert. That's not a risk with non-coding (or irrelevantly-coding) DNA, which means that in return for spending energy on copying junk DNA, we get space where even barely-useful changes will be net positive.

Is this obvious to experts? Completely stupid for reasons I don't know? Even a possibility worth discussing?

Re: No human genome has ever been completely sequenced

#32

Post by throwanem » Mon, Oct 23, 2017, 6:15 PM UTC

coldtea wrote: post #25

phyzome wrote: post #14

Earlier quoted context omitted.

As the article says, we know there's important stuff in those repetitive regions, it's just really hard to read.

Well: "“A lot of people in the 1980s and 1990s [when the Human Genome Project was getting started] thought of these regions as nonfunctional,” said Karen Miga, a molecular biologist at the University of California, Santa Cruz. “But that’s no longer the case.” " And: "“I’m between agnostic and a little skeptical that these bits will be important for disease, but maybe I’m saying that because we can’t read them,” Lande…

The "no such thing as junk DNA" claim comes from a paper which is, to say the least, controversial in the field. I would hesitate to take it as prima facie reliable, and in general would recommend looking with extensive skepticism upon popular reporting in this realm of scientific endeavor. After all, this very thread originates in a piece of popular reporting that only seems novel because all of the previous popular reporting has been wrong...

Re: No human genome has ever been completely sequenced

#33

Post by baxtr » Mon, Oct 23, 2017, 6:20 PM UTC

nether wrote: post #27

shpx wrote: post #12

Earlier quoted context omitted.

https://youtu.be/fCd6B5HRaZ8 is the best visualization of how the most popular type of DNA sequencer works (that I've found). Imagine you have a string of length 3 billion made by randomly choosing from 4 characters. Like this dna = ''.join(random.choices('atgc', weights=[30.9, 29.4, 19.9, 19.8], k=3_234_830_000)) you get to randomly sample 1 billion[3, page 7] overlapping substrings of length 200[3, page 7] with .1%…

Side note: your comment is one of the few times I've seen the code tag used for actual code on HN, rather than quotations or just indentation.

True, and unfortunately it does not render it properly, it‘s cut after 20 chars or so

Re: No human genome has ever been completely sequenced

#34

Post by [deleted] » Mon, Oct 23, 2017, 6:23 PM UTC

Bartweiss wrote: post #31

> * A gene called ARHGAP11B, which was created by one such duplication, causes the cortex to develop the myriad folds that support complex thought; SRGAP2C, also a duplication, triggers brain development.* A question I've never seen addressed: is one justification for junk DNA to create space for beneficial mutations? Obviously some mutations are actively harmful, but the reason most mutations are destructive is that…

[deleted]

Re: No human genome has ever been completely sequenced

#35

Post by pjschlic » Mon, Oct 23, 2017, 6:25 PM UTC

Bartweiss wrote: post #31

> * A gene called ARHGAP11B, which was created by one such duplication, causes the cortex to develop the myriad folds that support complex thought; SRGAP2C, also a duplication, triggers brain development.* A question I've never seen addressed: is one justification for junk DNA to create space for beneficial mutations? Obviously some mutations are actively harmful, but the reason most mutations are destructive is that…

If I recall correctly from my bioinformatcs classes (years ago) - the non-coding DNA still serve many functions - a protective role by containing sequences which stabilize the structure of the DNA, or providing binding sites used in promoting or suppress gene expression. The non-coding are recognizable by different characteristics from the coding sections. Not to mention the fact that by definition, at least half the sequences are just the complement of a coding sequence - so putting in stop codons before and after on the complement would be useful to make sure it's not expressed. Add in structural sequences to create preferences of where it's safe to swap genes with the sister chromosome DNA during meiosis, and all sorts of other things, and you end up with quite a but of non-coding DNA still serving a purpose.

Re: No human genome has ever been completely sequenced

#36

Post by nkrumm » Mon, Oct 23, 2017, 6:26 PM UTC

Bartweiss wrote: post #31

> * A gene called ARHGAP11B, which was created by one such duplication, causes the cortex to develop the myriad folds that support complex thought; SRGAP2C, also a duplication, triggers brain development.* A question I've never seen addressed: is one justification for junk DNA to create space for beneficial mutations? Obviously some mutations are actively harmful, but the reason most mutations are destructive is that…

Perhaps not exactly "junk dna" but you are right in your thinking about gene duplications... duplications are thought to promote "neofunctionalization" (a new function) or "subfunctionalization" (specialization).

See wikipedia [1] for an overview.

[1] https://en.wikipedia.org/wiki/Gene_duplication#As_an_evoluti...

Re: No human genome has ever been completely sequenced

#37

Post by searine » Mon, Oct 23, 2017, 6:30 PM UTC

Bartweiss wrote: post #31

> * A gene called ARHGAP11B, which was created by one such duplication, causes the cortex to develop the myriad folds that support complex thought; SRGAP2C, also a duplication, triggers brain development.* A question I've never seen addressed: is one justification for junk DNA to create space for beneficial mutations? Obviously some mutations are actively harmful, but the reason most mutations are destructive is that…

>A question I've never seen addressed: is one justification for junk DNA to create space for beneficial mutations?

Yes, gene/genome duplications can help create raw material for adaptation, or be adaptive by their own right.

>That's not a risk with non-coding (or irrelevantly-coding) DNA

It's not risk free. It's just less risky. There are all sorts of elements within the "intergenic" region of genomes which can impact fitness. Duplications in these regions can change the "dosage" of genes or the availability of DNA to be transcribed.

Duplicating these regions is mostly dependent on how tolerate the species is of dosage changes. Humans for example are very intolerant, while plants are very tolerant.

Also, please stop using "junk DNA". It is outdated term ;).

Re: No human genome has ever been completely sequenced

#38

Post by [deleted] » Mon, Oct 23, 2017, 6:30 PM UTC

nonbel wrote: post #20

slavik81 wrote: post #13

Earlier quoted context omitted.

The was flag killed. I vouched for this because I had the same question. What does it mean to have sequenced the human genome? If different individuals have a different genome, what is the human genome?

Not only do different individuals have different genomes, each cell from the same person will have different genomes. It is more like an "average" human genome, one that no actual cell has ever contained.

[deleted]

Re: No human genome has ever been completely sequenced

#39

Post by searine » Mon, Oct 23, 2017, 6:32 PM UTC

iskander wrote: post #3

It's strange that this article ends as an advertisement for PacBio sequencing (which can ~50k-60k base reads) but makes no mention of Oxford Nanopore (which has gotten megabase reads and keeps improving). Single molecule nanopore sequencing is on track to sequence across the centromeres of human chromosomes in the next few years.

The problem is Oxford Nanopore data has about a 30% insertion and deletion error rate. While PacBio is less than 1% indel and substitution error.

Don't get me wrong, the Minion is amazing, but it can't compare to PacBio in terms of quality... yet.

Re: No human genome has ever been completely sequenced

#40

Post by searine » Mon, Oct 23, 2017, 6:33 PM UTC

cycrutchfield wrote: post #22

iskander wrote: post #3

It's strange that this article ends as an advertisement for PacBio sequencing (which can ~50k-60k base reads) but makes no mention of Oxford Nanopore (which has gotten megabase reads and keeps improving). Single molecule nanopore sequencing is on track to sequence across the centromeres of human chromosomes in the next few years.

How many sequencers has Oxford Nanopore sold? It seems like it has perennially been a “in the next few years” technology.

I got mine as part of the beta almost two years ago. It's been in release since, and seems popular in the community. It's not Illumina HiSeq popular, but the cost is low enough that lots of people are experimenting with it.