Re: Part 1 (of 3): What are major aspects of evolutionary theory?


John Harshman wrote:
> Nic wrote:
>
> > anon1@xxxxxxx wrote:
> >
> >>>Even as recently as last month I was reading that haplotype blocks
> >>>were conserved in the same way linkage groups are; i.e. low
> >>>probability of being hit by a crossover. I had thus been regarding
> >>>the terms as synonymous.
> >>
> >>They are not synonymous.
>
> > Agreed. Whether they are compatible is more the question, or do they
> > assume incompatible underlying mechanisms? The alleged 'hotspots' seem
> > to be a new fact about the crossover mutation mechanism which
> > invalidates assumptions from before the genomics era, possibly
> > including the very assumptions the Morgan measure is based upon.
>
> Depends on their size. If these blocks are only a few thousand bases, or
> even a few hundred thousand, then nothing really changes. If they're
> millions of bases, then we get problems.

To say that, you have to have a view on how often crossover events
happen and how long it is since there was this population bottleneck.
I haven't looked up that information, let alone how big the blocks are
supposed to be.

> The average human gene is about 20kbp (the bulk of that being introns)
> and there's about twice that space on average between genes. So even
> with these blocks, unless they're very big, we should get recombination
> between adjacent genes.

I didn't realise the genes were spread out like that. In that case,
the haplotype blocks could indeed be an artifact. I had always
imagined the genes would be closer together because in the past there
must have been fewer chromosomes. But I guess that's silly because
chromosome number increases by accidental duplication, not by the
creation of new, empty ones. Still, it's hard to see how genes could
spread out to fill the space available. Maybe it's because insertion
mutations are guarranteed survivable if they land in the gaps between
genes.

> I pulled the numbers from here: http://cnx.rice.edu/content/m11317/latest/
>
> I would have to say that just browsing the genome my impression would
> have been that the average size of a gene was even larger than that.

Implying they are for proteins with structural roles rather than
catalytic?

> >> Genetically speaking, humans are incredibly similar to one another.
> >> Any two unrelated genome sequences differ at only one position in a
> >> thousand, on average. The 0.1 per cent difference, which amounts to
> >> about three million base pairs of DNA in total, ...
> >> Much genetic diversity (around 90 per cent) consists of single
> >> nucleotide polymorphisms (SNPs), ...
> >>(What do the other kinds of diversity consist of? Tandem repeats?
> >>Rearrangements? Duplications? Block deletions? Point inserts and
> >>deletes?
>
> All of the above.
>
> > How do you compare large block changes with point changes on a
> >>fair basis? For example, does a single block of 50 bases that gets
> >>duplicated count the same as 50 separate SNPs, or just 1 or 2 SNPs?)
>
> Depends on what you are trying to count. If you want (for some reason)
> to count simple sequence differences, it might count as 50. If you want
> to count evolutionary events (usually a more useful thing to count),
> then it's one. If you want to count the probability of it having
> happened identically more than once (i.e., homoplasy), that gets to be a
> complicated question.
>
> All those other kinds of diversity count for much fewer evolutionary
> events, or single mutations, than do the SNPs.
>
> > I *guess* the percentages are of loci with/without polymorphism, i.e.
> > it's real estate, with no weighting for higher degrees of polymorphism.
> > So 50 is 50 whether SNPs or not. I guess this, because surely they
> > would have to say if they meant anything else.
>
> I can't interpret this.

I meant they would look at the total number of base pairs different,
whether comparing two human beings from the same locality, from
different continents, or if comparing a human with a chimp, or with a
geranium. Any more complicated comparison would demand an explanation.

> I would guess that there are very few loci
> without polymorphisms. If the probability of a mutation is in the
> neighborhood of 10^-9 per site, per individual, per generation (and
> that's a reasonable ballpark figure), then most sites will experience
> multiple mutations per generation, somewhere within the population. That
> makes total polymorphism pretty much a meaningless number. And that's
> why mean polymorphism is the figure we count, and why frequency is
> important.
>
> [snip]
>
> >>Now by measuring the allelles of SNPs in lots of different people, we
> >>should be able to observe how widely distributed they are in various
> >>populations in different geographic areas, and from that information we
> >>should be able to estimate when each SNP first occurred due to point
> >>mutation. Likewise by mapping the haplotype blocks, in particular by
> >>measuring how widely distributed crossing-overs at boundaries between
> >>adjacent-block are compared to inheritance of the same ancestral pair
> >>of adjacent blocks, we may be able to estimate how long ago each
> >>crossing-over between two adjacent haplotype blocks occurred. Just like
> >>SNPs, new combinations of haplotype blocks due to crossing between
> >>blocks would tend to disappear except when such cross-overs occurred
> >>during times of population growth.
> >
> >
> > Tending to disappear? It seems that way, but the population does a
> > random walk, which has no 'tendency'.
>
> The great majority of all neutral mutations disappear. Is that a
> tendency? the frequency of a new mutation is 1/2N, and the probability
> of a neutral mutation eventually becoming fixed is its frequency.
> Therefore a new mutation has a probability of 1/2N of being eventually
> fixed, and a probability of (1 - 1/2N) of becoming extinct. Is that a
> tendency?

I know. A random walker starting one step in from the edge of a cliff
hasn't got the best of prospects, despite there being no bias to its
meanderings. Still, it's got 50:50 of staying one more round, which is
exactly the same as for the unmutated variant in my sister.

Nic

.

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