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Author Topic:   New genes in the Human lineage
Wounded King
Member (Idle past 2385 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 1 of 7 (533992)
11-04-2009 7:38 AM


Anyone familiar with the debates on this site is likely to have seen many references to the evolution, or rather sudden appearance, of the Nylonase gene. The Nylonase gene is thought to have arisen through a frame shift mutation giving rise to a novel open reading frame coding the nylon degrading enzyme.

This sort of de novo generation of a new gene is considered a very rare event, and little is known about such occurences as they are generally very hard to detect. Apart from Nylonase there are only a few known instances in Yeasts and Drosophila

A recent research paper in 'Genome Research' entitled 'Recent de novo origin of human protein-coding genes' looks for exactly these sort of genes in humans (Knowles and McLysaght, 2009).

Using a variety of sequence similarity search tools on several primate species, and information from a number of other organisms, the Authors identified 3 genes which produced protein products in human but not in any of the other primate lineages, or in other species that they studied. In the primate lineages all three genes shared specific sequence differences which meant that the sequence would not be transcribed or would produce a radically different protein if it was transcribed, certainly in the chimpanzee all three genes are considered non-coding.

The mutations producing the de novo genes are a single nucleotide subsitution removing a stop codon, a single nucleotide deletion causing a 'frameshift' and a 10bp insertion creating another 'frameshift' (is it really a frameshift if the original sequence is non-coding?).

The authors estimate that there are likely to be ~18 such de novo genes unique to the human lineage. They can only estimate because only a subset of human coding genes, ~4000, were suitable for their methods of analysis.

This is a really interesting paper, but what does it mean in terms of the debate between Evolution and Creation. Does the existence of these sort of mutations provide further evidence of the ability of random mutation to create functional sequences, albeit ones we don't really know the function of. Does the pre-existence of a sequence which in 1 small step can suddenly produce a full coding sequence for a new gene argue instead for some sort of front-loading style ID. How can the switch from coding to non-coding be encomapassed in the sort of informational metrics which come up in the EvC debate?

TTFN,

WK


Replies to this message:
 Message 3 by Kaichos Man, posted 11-07-2009 8:13 AM Wounded King has responded

    
AdminAsgara
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Message 2 of 7 (534000)
11-04-2009 8:57 AM


Thread Copied from Proposed New Topics Forum
Thread copied here from the New genes in the Human lineage thread in the Proposed New Topics forum.

    
Kaichos Man
Member (Idle past 2779 days)
Posts: 250
From: Tasmania, Australia
Joined: 10-03-2009


Message 3 of 7 (534365)
11-07-2009 8:13 AM
Reply to: Message 1 by Wounded King
11-04-2009 7:38 AM


G'day WK.

Interesting quote from Cold Spring Harbour Laboratory:

The prevailing wisdom in the field of molecular evolution was that new genes could only evolve from duplicated or rearranged versions of preexisting genes. It seemed highly unlikely that evolutionary processes could produce a functional protein-coding gene from what was once inactive DNA.

No wonder I was having so much trouble getting a straight answer on my "Adding Information to the Genome" thread.

So these new genes are thought to have evolved from junk DNA (though I can't understand why it's termed "junk DNA" when similar sequences are found inactive in other primates. You'd think they would differentiate between junk and an inactive gene).

In fact, this doesn't make sense. Why do they believe the genes originated from junk DNA, rather than from "rearrangements of existing genes"? The fact that the sequence doesn't code in primates doesn't mean it's not an existing gene, does it?

Highly frustrating that they don't know what these genes code for, other than the heightened activity of one in cases of leukemia.


"Often a cold shudder has run through me, and I have asked myself whether I may have not devoted myself to a fantasy." Charles Darwin

This message is a reply to:
 Message 1 by Wounded King, posted 11-04-2009 7:38 AM Wounded King has responded

Replies to this message:
 Message 4 by caffeine, posted 11-07-2009 9:51 AM Kaichos Man has not yet responded
 Message 5 by Wounded King, posted 11-08-2009 7:15 PM Kaichos Man has not yet responded

    
caffeine
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Message 4 of 7 (534374)
11-07-2009 9:51 AM
Reply to: Message 3 by Kaichos Man
11-07-2009 8:13 AM


Junk DNA
quote:
So these new genes are thought to have evolved from junk DNA (though I can't understand why it's termed "junk DNA" when similar sequences are found inactive in other primates. You'd think they would differentiate between junk and an inactive gene).

Inactive genes are junk DNA. Junk DNA is just a catch all term for sections of DNA that don't appear to be doing anything at the moment.


This message is a reply to:
 Message 3 by Kaichos Man, posted 11-07-2009 8:13 AM Kaichos Man has not yet responded

  
Wounded King
Member (Idle past 2385 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 5 of 7 (534494)
11-08-2009 7:15 PM
Reply to: Message 3 by Kaichos Man
11-07-2009 8:13 AM


No wonder I was having so much trouble getting a straight answer on my "Adding Information to the Genome" thread.

The reason you weren't getting an answer, or at least not one that satisfied you, was because you couldn't articulate a coherent concept of information that could actually be measured. People gave you lots of perfectly straight answers, you just didn't like the measures of information they were using. When you did give a specific measure or at least specific forms of mutation you were interested in, i.e., single nucleotide substitutions or duplications at various scales, people provided examples where they did have functional effects.

I can't understand why it's termed "junk DNA" when similar sequences are found inactive in other primates. You'd think they would differentiate between junk and an inactive gene

There is no way to distinguish between them in the absence of a reasonably sized coding region. The sequences don't have the sort of homologies we can use to identify functional genes in a pathway of common descent. There are lots of pseduogenic sequences in what is commonly thought of as 'junk DNA' that would be more easily identified as 'inactive genes'.

In fact, this doesn't make sense. Why do they believe the genes originated from junk DNA, rather than from "rearrangements of existing genes"? The fact that the sequence doesn't code in primates doesn't mean it's not an existing gene, does it?

The non-coding forms of the sequences aren't just found in the primates but also in other more distant species, which is why the most parsimonious conclusion is that they were newly generated in humans. The coding forms of these sequences currently appear unique to humans, so all the evidence is that these actually are novel genes. The lack of homology to other known proteins argues against an origin from the re-arrangement of existing coding sequences.

Highly frustrating that they don't know what these genes code for, other than the heightened activity of one in cases of leukemia.

Indeed. That and the lack of evidence for selection around the genes makes me wonder if maybe these particular sequences simply aren't functional, an interesting example of Kimura's theory. Although if the leukaemia associated gene was actually a causative factor you might think there would be some negative selection, that would probably depend on the type of leukaemia though since childhood leukaemias would be much more likely targets for selection. Lots of genes are non-specifically upregulated in cancers though so it may not have any causative role at all.

It is worth pointing out that they still don't actually know what the leukaemia associated one does, they just know that it's expression is upregulated in some cases of leukaemia.

TTFN,

WK

Edited by Wounded King, : No reason given.


This message is a reply to:
 Message 3 by Kaichos Man, posted 11-07-2009 8:13 AM Kaichos Man has not yet responded

    
Wounded King
Member (Idle past 2385 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 6 of 7 (538671)
12-09-2009 5:13 AM


*bump*
Just a bump since Kaichos man was asking about new genes in a different thread.

TTFN,

WK


    
Wounded King
Member (Idle past 2385 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 7 of 7 (662521)
05-16-2012 11:49 AM


A new article and more de novo genes
While addressing a post by Zaius in another thread I came across another article using a similar methodology to Knowles and Mclysaght.

In this case Wu et al. (2011) found considerably more putative de novo protein coding genes in the Human genome.

Wu et al. 2011 writes:

De Novo Origin of Human Protein-Coding Genes
The origin of genes can involve mechanisms such as gene duplication, exon shuffling, retroposition, mobile elements, lateral gene transfer, gene fusion/fission, and de novo origination. However, de novo origin, which means genes originate from a non-coding DNA region, is considered to be a very rare occurrence. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee, supported by both transcriptional and proteomic evidence. It is inconsistent with the traditional view that the de novo origin of new genes is rare. RNA–seq data indicate that these de novo originated genes have their highest expression in the cerebral cortex and testes, suggesting these genes may contribute to phenotypic traits that are unique to humans, such as development of cognitive ability. Therefore, the importance of de novo origination needs greater appreciation.

They finish with a slight caveat ...

many of these new genes are expressed at very low levels in the 11 tissues that had available RNA-seq data. These results indicate that many of these genes may play only weak biological roles, or that their functions are not well established.

So perhaps these genes are not strong contenders for being clear, functional, beneficial de novo mutations. There certainly does seem to be growing evidence for these de novo coding sequences arising and persisting much more commonly than one might expect.

As an interesting side note they emphasise that many of these genes are expressed in the testes and cite a review paper by Henrik Kaessmann (2010) which discusses various types of novel gene origination and notes that many such genes seem to strongly favour expression in the testis. Kaessmann put forward the suggestion, what he calls the "Out of the Testis hypothesis", that the testis form a sort of testing ground for new genes due to the very permissive transcriptional state of the chromatin in the testis. This reminded me strongly of the somewhat castles in the sky hypothesis (Message 133) I threw together in one of the many threads discussing Barbara Wright's work as to how the sort of mechanisms she describe might operate in an organism with a germ/soma divide. Kaessmann extends the idead though by suggesting that once they have been through such a proving ground the genes could subsequently be incorporated into functioning in somatic tissues.

TTFN,

WK


    
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