Re: What goes around comes around

From: Pim van Meurs <>
Date: Sat Oct 08 2005 - 15:23:29 EDT

Cornelius Hunter wrote:

> Preston:
>> Here's the ref I was thinking of. These guys found over 900
>> orthologous insertions in a 1.5 Mb alignment of human and chimp. So,
>> extrapolating we're talking millions, really. The total number in a
>> set of 9 species that were fully sequenced in this segment contained
>> over 1000 sites. The total is not much higher for the whole group,
>> because the more distant species (dog, cat, cow etc) contained only a
>> few sites in this region. This is the same data that Frances Collins
>> referred to in his PSCF article. If I remember right there were ~50
>> anomalous insertions in the nine species set, but I'm not sure. This
>> is a complicated paper and I haven't studied it carefully yet. I'm
>> sure you will find much to object to. :)
>> Genome Res. 2005 Jul;15(7):998-1006.
>> Orthologous repeats and mammalian phylogenetic inference.
>> Bashir A, Ye C, Price AL, Bafna V.
>> Determining phylogenetic relationships between species is a difficult
>> problem, and many phylogenetic relationships remain unresolved, even
>> among eutherian mammals. Repetitive elements provide excellent
>> markers for phylogenetic analysis, because their mode of evolution is
>> predominantly homoplasy-free and unidirectional. Historically,
>> phylogenetic studies using repetitive elements have relied on
>> biological methods such as PCR analysis, and computational inference
>> is limited to a few isolated repeats. Here, we present a novel
>> computational method for inferring phylogenetic relationships from
>> partial sequence data using orthologous repeats. We apply our method
>> to reconstructing the phylogeny of 28 mammals, using more than 1000
>> orthologous repeats obtained from sequence data available from the
>> NISC Comparative Sequencing Program. The resulting phylogeny has
>> robust bootstrap numbers, and broadly matches results from previous
>> studies which were obtained using entirely different data and
>> methods. In addition, we shed light on some of the debatable aspects
>> of the phylogeny. With rapid expansion of available partial sequence
>> data, computational analysis of repetitive elements holds great
>> promise for the future of phylogenetic inference.
> Preston:
> These results are predicated on the assumption that evolution is true.
> Of course there is nothing wrong with this (Kuhn calls it "normal
> science"), but we need to be careful in using the results outside of
> normal science; that is, as evidence for evolution.
> In this case, when genomes were first being studied and people started
> systematically looking at SINEs, they knew of no insertion site
> preference and the SINEs appeared at the same locus in similar
> species. So, assuming evolution is true, the obvious interpretation is
> that these derive from a common ancestor rather than from independent
> insertion events in the two lineages. So you had statements like this
> being made about 5 years ago:
> "There is no compelling empirical or theoretical reason to expect
> SINEs to commonly insert at the exact same locus or be transferred or
> removed from the genome in any way that is ambiguous by standard
> methods of experimental detection." [Shedlock, A.M., Milinkovitch,
> M.C., Okada, N., "SINE Evolution, Missing Data, and] the Origin of
> Whales," Syst. Biol. 49(4):808-817, 2000 (page 810).
> This statement has, imbedded in it, the assumption that evolution is
> true. Lift that assumption, and things become less obvious. In fact,
> since then, SINEs have been found at the same insertion site in
> distant species, such that common descent cannot be the cause. In
> these cases, even those who presuppose evolution is true must agree
> that there is something going on, such as an insertion site preference.
> But because of the history of thought here in the past decade or so,
> the assumption remains that SINEs (generally) do not have insertion
> site preferences. The cases where insertion site preference is
> unavoidable, even under evolution, are viewed as the exceptions, not
> the rule. So here is the opening statement of the paper you referenced:

More confusion here it seems. You state that the statement that there is
no compelling biological or theoretical reasons to expect SINE's to
commonly insert at the same location, has embedded in it the assumption
that evolution is true. I fail to see how you reach this conclusion.

Shedlock in another 2000 paper writes

Volume 22, Issue 2 , Pages 148 - 160
SINE insertions: powerful tools for molecular systematics Andrew M.
Shedlock Norihiro Okada

<quote>Two contrasting models of SINE evolution have emerged from
available evidence: the master gene model (27) and the multiple source
gene model.(28) Each of these supports different predictions regarding
the possible role of selection, expected amplification rates,
accumulation of sequence diversity within a SINE family and the
subsequent formation and distribution of subfamilies over evolutionary

While Cornelius may 'argue' that there could be compelling empirical or
theoretical reasons to expect SINEs to commonly insert at exact same
locations, he needs to do more than that and follow in the footsteps of
the many scientists who based on the SINEs formulated testable models of
SINE evolution.

Based on these testable models, it was shown that phylogenies were
recovered that were indeed similar to other methods of phylogenetic
reconstructuion showing once again the fact of common descent.

Based on these models, it seemed that SINEs may provide a character type
free from ambiguities.

<quote>The keystone to the intrinsic value of SINEs as systematic
characters is their widely dispersed, irreversible re-integration into
the host genome. It is worth highlighting that these features of SINE
genetics are well-established phenomena and should not be confused with
less clear aspects of SINE biochemistry, such as the precise mechanism
of how SINEs acquire reverse transciptase from other sources (e.g.,
LINEs) during the amplification process, or whether the master or
multiple source gene model most accurately explains empirical
patterns of variation in divergent SINE sequences

Although hotspots of insertion may ocuur in exceptional cases (H.A.
Wichman, unpublished data), and human Alus may preferentially integrate
in locally AT-rich or regions of R-bands of chromatin (28,39), SINEs are
commonly found dispersed throughout the genome and can be primed for
retroposition at nicked sites.(19,22,40) Furthermore, there is still no
evidence of any process that specifically removes SINEs from chomosomal
DNA despite more than a decade’s worth of intense analysis of patterns
of retroelements in humans and other eukaryotes (see numerous detailed
review papers (4,8,13,14,18,21,25,30,41)). Large, non-specific SINE.</quote>

So far it seems that all this is based on good science, which 'happens'
to support evolutionary theory. No big surprise here really.

<quote>Large, non-specific SINE deletions (e.g., unequal recombination
between short repeats to either side of an insert) are relatively rare
events that would also be detected by PCR diagnostics and comparative
sequence inspection during SINE insertion analysis (see following
section on Applications). Likewise, horizontal transfer of SINEs is
severely restricted by their non-autonomous amplification. Even if it
does occur occasionally between
between species (38, 42), it is not problematic for the general use of
SINEs as systematic characters: it is extremely unlikely that a SINE
would be horizontally transferred exactly at the same locus
independently in two different taxa.
Thus, the probablilities of a SINE either inserting precisely in the
same locus in two different unrelated lineages in a convergent manner or
else being precisely excised from the genome and leaving no detectable
trace are both exceedingly minute, and for all practical purposes, can
be ignored.

I realize that the number of papers on SINE may prevent one from fully
understanding the extent of research in this area. Of course, if one
wishes to propose a 'common process' 'explanation', one has to do more
than merely raising the plausibility.

Now lets come back to a quote presented by Cornelius

"There is no compelling empirical or theoretical reason to expect SINEs
to commonly insert at the exact same locus or be transferred or removed
from the genome in any way that is ambiguous by standard methods of
experimental detection." [Shedlock, A.M., Milinkovitch, M.C., Okada, N.,
"SINE Evolution, Missing Data, and] the Origin of Whales," Syst. Biol.
49(4):808-817, 2000 (page 810).

The paper addresses a recent 'controversy' and Shedlock et al comment that

<quote>In their recent assessment of morphological and molecular
evidence for inferring cetacean ancestry, Luckett and Hong (1998) badly
misconstrue how SINEs evolve, misinterpret how they are used for phylogeny
inference, and incorrectly dismiss evidence from SINEs that conclusively
demonstrate paraphyly of the Artiodactyla. We believe this is a serious
problem that is counterpoductive to advancing an accurate understanding
of cetacean evolution and unfortunately promotes a negative view
regarding the value of molecular data that goes
well beyond the current debate about whale origins.</quote>

They argue:

<quote>Clearly, properly understanding the nature of SINE retroposons
and how they evolve is fundamental to their intelligent application as
phylogenetic tools. Several comprehensive reviews of retroposon
evolution, and intrinsic value as molecular systematic markers are
available (Weiner et al., 1986; Deininger and Batzer, 1993; Schmid,
1996; Shedlock and Okada, 2000). Nevertheless, it is instructive to
review here selected aspects
of SINE molecular biology andevolution that are especially relevant to
their use for phylogeny inference.</quote>

In other words, before one uses SINEs as evidence, one has to understand
how they evolve.

So now we get to the quote

<quote>There is no compelling empirical or theoretical reason to expect
SINEs to commonly insert at the exact
same locus or be transferred or removed from the genome in any way that
is ambiguous by standard methods of experimental detection. We emphasize
that absence of SINE detection is not to be confused with detection of
SINE absence, and aspects of this important methodological issue are
discussed below. Obviously, as more SINE data accumulate for various
taxonomic groups, estimating the level at which these basic assumptions
are met should become possible.
Certainly, based on all available evidence, SINE markers should continue
to present levels of homoplasy resulting from reversals, convergence,
and parallelismthat are far less than those typically observed in DNA
data and many morphological comparisons.

They return to the methodological issue later in the paper

<quote>We have found this latter issue regarding missing data to be a
particularly common point of confusion regarding the proper
interpretation of evidence for SINE insertion and its methodological
integrity. Figure 4
diagrams the problem of confusing the absence of SINE evidence with the
evidence of SINE absence, and how this can lead to drawing erroneous
conclusions about SINE results and sampling design. Such confusion
is a fundamental problem in the comments published by Luckett and Hong
(1998) that are now being cited inappropriately (e.g., Heyning, 1999a)
as a careful reconsideration of molecular evidence regarding artiodactyl


As reviewed above, it is well established that copies of the same SINE
shared in two different taxa are derived from the same historical
insertion event in the germ line of a common ancestor, and thus deŽne a
group. Comparative studies suggest that the likelihood of SINEs being
independently inserted at the same locus in different lineages (or
precisely excised) is exceedingly small; furthermore, cases of
horizontal transfer are also not problematic for SINE insertion analysis
because diagnosis is focused on the presence or absence of a SINE at
a particular locus. Hence, these characters can be expected to show
exceptionally low levels of noise from reversals, parallelisms, and
convergences. </quote>

Hope this helps clarify how SINE evolution has been well established
through hard scientific inquiry.
Received on Sat Oct 8 15:25:17 2005

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