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

anon1@xxxxxxx wrote:

>>I don't know what you mean by "haplotype block".
>
>
> Any single contiguous segment of DNA that appears to have evolved as a
> single unit for hundreds of thousands of years according to the
> preliminary haplotype-map summary report that I saw in _Science_ a few
> weeks ago. Meiosis seems to have mixed-and-matched among the different
> blocks, yet seems to have kept each single block intact for all that
> time. At least that's the impression I got from reading the report.
> I had always thought that DNA can break just about anywhere, that
> some places it breaks slightly more often than other places, but in
> general there's only a small variation between hot spots and cool spots
> in regard to breaking and crossing during meiosis. But the report seems
> to say that old idea was wrong, that there's such a drastic difference
> between hot and cool spots that to a good approximation the chromosomes
> are strictly divided into fixed blocks that act as units during meiosis.

Very interesting if so, though it contradicts all sorts of other data.
But I can work with that.

> SNPs can be tracked through the generations, to detect ancestry along
> mixed male/female lines of descent, but because any one SNP has only
> four possible states, the same state recurs at random many times, so if
> you see the same exact rare SNP in two distant populations you can't be
> sure whether there was recent gene flow between them or the same SNP
> recurred by chance in both places.

> But any single haplotype block has *many* different states, and each
> evolutionary line accumulates occasional mutations which don't recur in
> the same exact pattern along different evolutionary paths, so seeing
> the same identical haplotype block in two remote populations definitely
> shows recent gene flow between them, more recent than the last mutation
> in that particular block within either population.
>
> So if that's true, haplotype blocks offer a really powerful way to
> detect tiny bits of gene flow between distant populations, such as if a
> single explorer wandered from one to the other and left one or two
> descendents who then left more descendents such that after hundreds or
> thoudsands of generations a few of the haplotype blocks from that
> invidiual explorer might remain in the population.
>
> (And if two very similar haplotype blocks are found, it indicates
> semi-recent gene flow, more recent than the bulk of mutations, but
> older than the very latest mutations after the gene-flow occurred.)
>
> The haplotype tool is much more powerful than the mitochondrial or Y
> method, because a lot of different haplotype blocks are passed from a
> single individual, instead of just one set of intact mitochondria or
> one Y chromosome, and then these blocks are split from each other as
> they are passed to subsequent generations, so an entire population with
> a single common ancestor is likely to each have a few blocks from that
> one ancestor mixed in with blocks from the many other ancestors equally
> far back in generations. In theory, if we knew the genomes of *every*
> individual at a certain time, then by matching haplotype blocks many
> generations later we can determine exactly which modern individuals are
> descended from exactly which ancestors. But more likely the best we can
> do is measure the current genome of all living individuals in each
> local population that is tightly inbred, and extrapolate back to the
> ancestors who had the same set of haplotype blocks (modulo mutations
> since then), and then detect any discrepancies from this neat model
> which would indicate any gene flow from one such tight group to/from
> another. If we could get DNA from several Neandertals, and thereby
> deduce what haplotype blocks they had, we might in fact be able to
> detect whether any modern humans have even one such
> distinctly-Neandertal haplotype block.

Thanks for the information. I'm a bit dubious about the constancy of
these haplotype blocks. How big are they?

>>Ah, here you are apparently talking about frequency of recombination.
>>Is "haplotype block" some kind of synonym for "linkage group"?
>
> Checking online definitions:
> <http://dictionary.reference.com/search?q=linkage%20group&db=*>
>
> A pair or set of genes on a chromosome that tend to be
> transmitted together.
> Yes, that's part of what I mean, except I mean they are transmitted
> together virtually without exception for tens or hundreds of thousands
> of years, not just that they tend to be transmitted together slightly
> more often than at randon over a single generation.
>
> : a set of genes at different loci on the same chromosome that except
> for crossing-over tend to act as a single pair of genes in meiosis
> instead of undergoing independent assortment
> No, I mean that *in*spite* of crossing-over they *nevertheless* remain
> linked, i.e. crossing-over simply doesn't "ever" happen (not in a
> hundred thousand years) between them.
>
> n : any pair of genes that tend to be transmitted together; "the genes
> of Drosophila fall into four linkage groups" [syn: linked genes]
> No, not at all. That definition simply means they are on the same
> chromosome (Drosophila has four chromosomes, as we all know from
> high-school biology), so there is *some* (possibly very weak) linkage
> between them, that they are not *totally* independent of each other.
>
> <http://www.biochem.northwestern.edu/holmgren/Glossary/Definitions/Def-L/linkage_group.html>
> A group of gene loci known to be linked; a chromosome. There are as
> many linkage groups as there are homologous pairs of chromosomes.

This definition is wrong. A chromosome would have to be very small to
form a single linkage group under most recombination rates. Or have a
special mechanism to prevent recombination.

> No! That's most definitely not what I mean here. (Note that "syntenic"
> means the same thing, but is unambiguous, applies to *any* two loci on
> the same chromosome, regardless of whether the linkage is strong enough
> to detect by standard tests, presumably Mendel-type breeding
> experiments.)

Agreed. That was a terrible definition of "linkage group".

> <http://opbs.okstate.edu/~melcher/MG/MGW1/MG111122.html>
> Ah, a fine Web site with lots of quotes to mine, such as:
> * Markers that have measurable recombination frequencies are said to
> be linked.
> * Markers related through a chain of linkage constitute a linkage
> group.
> Ah, so a "linkage group" is a maximal connected set of markers (loci)
> via the pairwise "linked" property (presumably meaning not easily
> separable by recombination, which is easier for me to understand than
> the verbage in the definition quoted). In most cases that would imply
> that such a maximal connected set is a whole chromosome. It's roughly
> analagous to a "ring species" which is a maximal connected set via
> pairwise ability-to-mate, or maximal-connected-graph in any other model
> that has binary links between nodes.
> * As more and more markers are studied, linkage groups become larger
> (and the number of groups smaller) until the number of linkage
> groups equals the number of chromosomes.
> So technically, "linkage group" is not globally defined for a species,
> rather it's defined contingent on a given set of markers under study.
>
> (SIde remark: When two ancestral chimp/human chromosomes joined
> end-to-end to yield a single human chromosome, two "linkage groups"
> were merged to form just one. In particular, genes that were near the
> joining ends of the original chromosomes, suddenly changed from being
> totally unlinked to being very closely linked. I wonder how such new
> linkage affected subsequent evolution of those loci? In particular, I
> wonder whether those two joined ends are now parts of a single
> haplotype block or parts of two adjacent haplotype blocks?)
>
> <http://66.102.7.104/search?q=cache:APrIlzHRp6wJ:hal.weihenstephan.de/genglos/asp/genreq.asp%3Fnr%3D519+linkage+disequilibrium&hl=en&ie=UTF-8>
> Nice definition:
> Linkage - An association in inheritance between characters such that the
> parental character combinations appear among the progeny more often
> than the non-parental.
> Note that any linkage, no matter how weak, qualifies for that definition.
> Connected in that way is not at all what I mean by "haplotype block"
> wherein all characters (or loci or markers) are virtually 100% linked
> over many generations.
>
> And for fun, slightly side topic, see this attempt to clear confusion
> regarding "linkage" vs. "linkage disequilibrium":
> <http://linkage.rockefeller.edu/wli/lld.html>
>
> Due to the ambiguity of definition, and the fact that the centroid of
> the various definitions simply defines linkage group as the contents of
> a chromosome,

No, that's not the centroid. The centroid would refer to non-independent
assortment.

> which is *not* what I mean, I think I'll avoid using
> that standard term when I mean the more specific kind of longterm
> linkage discovered by the haplotype-map project, where there are
> several different such blocks on each single chromosome.

Can you define "several" here? How long are these blocks? If they're so
big as to have only "several" per chromosome, then chromosomal mapping
by linkage would be impossible, and as this has been done with humans as
well as other species, I'm going to suppose that there are lots and lots
of blocks per chromosome, so they don't show up at all at the scale of
linkage maps.

> I'm going to cut my reply here, and respond to later remarks in another
> posting.
> .
>

.

Relevant Pages

  • Re: Part 1 (of 3): What are major aspects of evolutionary theory?
    ... Of the various definitions of "linkage group" ... centimorgans is numerically equal to the recombination frequency ... observe a small number of different haplotype blocks compared to what ...
    (talk.origins)
  • Re: Part 1 (of 3): What are major aspects of evolutionary theory?
    ... >> were conserved in the same way linkage groups are; ... > in the same linkage group. ... > observe a small number of different haplotype blocks compared to what ... > allelle each at the two sites, but then a mutation happened at one of ...
    (talk.origins)
  • Re: Part 1 (of 3): What are major aspects of evolutionary theory?
    ... > I wasn't talking about independent assortment between haplotype blocks. ... set of markers, with sufficient gaps between them that the markers near ... one end of a chromosome aren't linked with markers near the other end, ... chain all the way from a to z, hence only one large linkage group ...
    (talk.origins)
  • Re: Part 1 (of 3): What are major aspects of evolutionary theory?
    ... to more than 100 million per chromosome. ... >> many linkage groups as there are homologous pairs of chromosomes. ... something portrayed as just a linkage map, with two genes indicated at ... codon and ends with a nonsense codon. ...
    (talk.origins)
  • Re: Making sense of HLA (I)
    ... A morgan is a length of recombination. ... had determined the 'linkage map' of the chromosome ... Did you know the word "linkage group" is the old ... Suppose I have a gene which is an allele at locus D allele 1 ...
    (sci.archaeology)