From owner-recombination@net.bio.net Thu Aug 01 23:00:00 1996 Path: biosci!agate!howland.reston.ans.net!vixen.cso.uiuc.edu!newsfeed.internetmci.com!hookup!news.nstn.ca!newsflash.concordia.ca!news.mcgill.ca!news From: mdty@musica.mcgill.ca Newsgroups: bionet.molbio.recombination Subject: RE: Significance of cM sexual dimorphisms Date: 2 Aug 1996 14:57:18 GMT Organization: McGill University Computing Centre Lines: 73 Message-ID: <4tt50e$lt9@sifon.cc.mcgill.ca> References: <199607312317.TAA29581@atlas.odyssee.net> NNTP-Posting-Host: 198.168.147.137 X-Newsreader: SPRY News 3.03 (SPRY, Inc.) In discussion of Mike Lichten' comments, Graham Dellaire wrote: > dellaire@ODYSSEE.NET ("Graham Dellaire") writes: > > > > > From: lichten@helix.nih.gov (Michael Lichten) > > To: recom@net.bio.net > > Subject: Re: Significance of cM sexual dimorphisms > > Date: Wednesday, July 31, 1996 11:56 AM > > > > I am enjoying reading this discussion! Just a couple of comments: > > > > 1. The most prominent sexual dimorphism in humans and mice is in then > > terminal localization of crossovers. In male meiosis, a significant > class > > of crossovers are telomeric or sub-telomeric; in females, they are more > > "uniformly" distributed. The best data for this is from Hulten's group > > (Chromosoma 104:223-7 and 104:308-14, which look at chiasmata > > localization. I have heard that the mouse mapping data is also > consistent > > with this notion, or at least is becoming more so as more terminal > markers > > emerge. > > > Hello all, > > A recent paper in PNAS by a group in China (April 1996, vol 93 pp > 2795-2800) > showed that telomeric sequences located terminally were associated > with smaller loops of DNA (loop domains) vs. telomeric sequences found > interstatially. the work was done in wild and transgenic mice > Thus packing of similar sequences can differ based on relative location > along the chromosome. The authors suggest that high recombination rates > at the telomeres of mice and humans correlates with shorter loop lengths > and this "somehow" may provide an idea of a mechanical basis for the > phenomenon.... > > Well shorter loops of DNA might mean that the DNA is more highly > constrained topologically and perhaps a more likely to be nicked or have > double strand breaks (either due to strain or as being a better substrate > for topoisomerase etc). Alternately, to be the devils advocate, their > observation seems a little paradoxical. Tighter packaging, i.e. smaller > loops, would mean less accessibility to proteins involved in > recombination. Apparently this is not the case! For sometime now various > groups have proposed that the nuclear matrix plays a central role in DNA > metabolism. Perhaps having smaller loops of DNA could mean greater access > to proteins within the matrix. Topo II isomerase is a major component of > the matrix and is a good candidate for an initiator of recombination. > Transcripition for instance has been hypothesized to occur at the borders > of chromosomal domains (Cremer et al. 1993) and that active genes are > found closer to the matrix (Ward and Coffey, 1991 also see a really > attractive Channel Model of Nuclear Structure by Razin and Gramova in > Bioessays (vol17 (5), 1995)). Perhaps too, recombinationally active DNA > is associated with the matrix. Let us not to forget there is many many difference between telomer sequences at ends of the chromosome and internal located. As I recalled, the ends of chromosome in mammalian cells are not free but is appeared to attach to the nuclear envolope. There is also appears to be a complex of protein and telomer sequence at the ends of chromosome (telochore) (Suja and Rufas, Chromosome Research 2:361-368). This topological constraint may contributed to the above observations. The chromosomal structure at or near the site of recombination may,therefore, influence the frequency of recombination at that site. The topology of the DNA in transcription, and replication may be a subset of these chromosomal structures. > > Cheers... I am looking forward to any comments Terry Chow McGill Unviersity mdty@musica.mcgill.ca From owner-recombination@net.bio.net Fri Aug 02 23:00:00 1996 Path: biosci!GPU.SRV.UALBERTA.CA!hastings From: hastings@GPU.SRV.UALBERTA.CA (P Hastings) Newsgroups: bionet.molbio.recombination Subject: Conversion gradients Date: 3 Aug 1996 09:54:50 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 29 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Rik Myers tells us that he has suggested using gene conversion gradients to find promotor regions. I feel that I must ask whether I have missed something which makes this a reasonable proposition, because using the inputs available in my head, it seems to me to be a lot of work with a high risk of telling nothing, and not much information if it succeeds. The inputs I start from are as follows: Many loci are immappable. In this situation there is no conversion gradient and if there were it could not be related to map possition because there is no semblance of additivity of recombination frequencies or even an inequality of R1 and R2 from which to construct a map. Examples of this are seen in SUP6 in yeast and several loci in Neurospora. It may be a widespread phenomenon which is not often reported because such data would be difficult to publish. Even in a mappable locus, there may be only weak polarity in overall conversion frequencies. Variation due to marker effects can mask possition dependent effects. If you get a map and find polarity, you may not assume that the direction of transcrption is the same as as the conversion gradient, high to low, since there are at least two exceptions to that in the very few cases for which the correlation is known. The exceptions I know of are his1 and his2 in yeast. So Rik. have I missed something? Best wishes, Phil. From owner-recombination@net.bio.net Fri Aug 02 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET ("Dellaire, Graham") Newsgroups: bionet.molbio.recombination Subject: RE: Significance of cM sexual dimorphisms (accessibility) Date: 3 Aug 1996 10:52:01 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 94 Sender: daemon@net.bio.net Distribution: world Message-ID: <199608031758.NAA25405@atlas.odyssee.net> NNTP-Posting-Host: net.bio.net >Date: Fri, 02 Aug 1996 12:32:44 >To: mdty@musica.mcgill.ca >From: "Dellaire, Graham" >Subject: RE: Significance of cM sexual dimorphisms > >In Terry`s Reply > > >.. Perhaps having smaller loops of DNA could mean greater access >>> to proteins within the matrix. Topo II isomerase is a major component of >>> the matrix and is a good candidate for an initiator of recombination. >>> Transcripition for instance has been hypothesized to occur at the borders >>> of chromosomal domains (Cremer et al. 1993) and that active genes are >>> found closer to the matrix (Ward and Coffey, 1991 also see a really >>> attractive Channel Model of Nuclear Structure by Razin and Gramova in >>> Bioessays (vol17 (5), 1995)). Perhaps too, recombinationally active DNA >>> is associated with the matrix. >> >>Let us not to forget there is many many difference between telomer sequences at ends of the >>chromosome and internal located. As I recalled, the ends of chromosome in mammalian cells are not >>free but is appeared to attach to the nuclear envolope. There is also appears to be a complex of >>protein and telomer sequence at the ends of chromosome (telochore) (Suja and Rufas, Chromosome >>Research 2:361-368). This topological constraint may contributed to the above observations. >> >>The chromosomal structure at or near the site of recombination may,therefore, influence the >>frequency of recombination at that site. The topology of the DNA in transcription, and replication may >>be a subset of these chromosomal structures. >>> >>> >> Cheers... I am looking forward to any comments >> >> >>Terry Chow >>McGill Unviersity >>mdty@musica.mcgill.ca >> > Terry, > >Nail on the head. I think it is becoming more and more accepted that to increas recombination frequencies and targeting in mammalian cells (and plants, and probably Drosophila....although the lower eukaryotes and prokaryotes are already very good at homologous recombination so increasing the frequency is a moot point) you need to alter chromatin structure such that the DNA is more accessible. One explaination for decreasing homologous recombination frequencies in ES cells vs. differentiated cells such as fibroblasts is that the structure of chromatin may become increasingly inaccessible during the course of differentiation. A simple correlation would be the fact that a) almost any piece of DNA can act as a replication origin in ES cells (i.e. more replication origins firing in ES cells than in differentiated cells) and b) transcription of batteries of genes is restricted in different tissues, reflecting different tissue specific chromatin structures (local not global... which would be assumed to be more or less the same in all somatic tissue) and therefore accessibilities. > >The note on telomere localization at the nuclear envelope is interesting.... I remember this as well, and I would like to add the results of Henikoff and the Sedat Groups. They found independently that the brown locus in Drosophila, which is involved in a transvection phenomenon that involves variegated expression of the gene(where the mutant allele alters (silences) the good copy of the allele on another homolog in "trans"), shows an association with centromeric repeats which may provide a mechanism for silencing. So the bottom line was that here localization of a gene domain to a region of the nucleus it does not normal occupy altered the transcription of the gene. > > >Just a quick note ...thanks for the input Terry! > > >Graham > > > > > > ++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Graham Dellaire Snail Mail: Faculty of Medicine Institut du Cancer de Montreal Div. of Experimental Medicine Centre de Recherche McGill University Louis Charles-Simard Montreal, Quebec, Canada Montreal, Quebec, Canada H2L 4M1 Voice:(514)876 6936 e-mail:dellaire ++++++++++++++++++++++++++++++++++++++++++++++++++++++++ From owner-recombination@net.bio.net Sat Aug 03 23:00:00 1996 Path: biosci!GPU.SRV.UALBERTA.CA!hastings From: hastings@GPU.SRV.UALBERTA.CA (P Hastings) Newsgroups: bionet.molbio.recombination Subject: Re: Conversion gradients (fwd) Date: 4 Aug 1996 09:46:59 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 21 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net ---------- Forwarded message ---------- Date: Sat, 3 Aug 1996 14:13:10 -0400 From: Graham Dellaire To: P Hastings Subject: Re: Conversion gradients Phil, I forgot to send the mail I sent you to the news group as well. If you could forward it to recom@net.bio.net, I would appreciate it. Lots of references from me...hehe you can guess I am in the throws of writing up a paper. Cheers, Graham Dellaire From owner-recombination@net.bio.net Sat Aug 03 23:00:00 1996 Path: biosci!GPU.SRV.UALBERTA.CA!hastings From: hastings@GPU.SRV.UALBERTA.CA (P Hastings) Newsgroups: bionet.molbio.recombination Subject: Re: Conversion gradients (fwd) Date: 4 Aug 1996 09:47:43 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 54 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net ---------- Forwarded message ---------- Date: Sat, 3 Aug 1996 14:10:31 -0400 From: Graham Dellaire To: P Hastings Subject: Re: Conversion gradients > hastings@GPU.SRV.UALBERTA.CA (P Hastings) writes: > Rik Myers tells us that he has suggested using gene conversion gradients > to find promotor regions. SNIP Paste > > If you get a map and find polarity, you may not assume that the > direction of transcrption is the same as as the conversion gradient, high > to low, since there are at least two exceptions to that in the very few > cases for which the correlation is known. The exceptions I know of are > his1 and his2 in yeast. > > So Rik. have I missed something? > Best wishes, Phil. > > Good point Phil, As Michael Lichten pointed out you don`t need transcription to have open chromatin and therefore the potential for gene conversion. I have caught some readings on differential silencing in yeast during the cell cycle. There are instances.... for example at the HMLalpha locus (Uv damage in temp sensitive mutants, Terleth et al. (1989 in NAR 17: 4433) where you can have increase in accessibility in G2 to M phase to proteins involved in repair but the locus is still silenced for transcription. So you could potentially have recombination events here but you still have silenced transcription. The details of the cell cylce component of recombination and accessibility is just beginning to be explored. Another study shows that silencing at the telomeres (Ura 3 experiments from Gotschling et al. (cell 1990, 63:751)) can be alleviated in yeast by the protein Ppr1p only in G2 to M phase and not prior to S phase indicating remodeling of chromatin during DNA sythesis may play and important role in silencing phenomenon. Swi/SNF and Rad54 on the other hand are implicated in chromatin remodeling independent of replication. Just a few jottings, Nice to have the ideas flowing. Cheers all, Graham Dellaire Experimental Medicine McGill University From owner-recombination@net.bio.net Sun Aug 04 23:00:00 1996 Path: biosci!rutgers!csn!nntp-xfer-1.csn.net!news-2.csn.net!csn!nntp-xfer-2.csn.net!tali.UCHSC.edu!essex.UCHSC.edu!binstoct From: Teresa Binstock Newsgroups: bionet.molbio.recombination Subject: RE: Signif of cM sexual dimorphisms (epigenetic, heritable) Date: Mon, 5 Aug 1996 02:12:59 -0600 Organization: University of Colorado, Health Sciences Center Lines: 41 Message-ID: References: <199608031758.NAA25405@atlas.odyssee.net> NNTP-Posting-Host: essex.uchsc.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: <199608031758.NAA25405@atlas.odyssee.net> Phil Hasting's points about not-knowability are important yet do not seem to detract from a basic issue arising from juxtaposing onto human chromosome cM descriptions the Shiroishi et al findings of (i) a specific cis-gene that appears to control recombo rates in at least one fairly small segment of the murine MHC, and (ii) the trans-gene epigenetic control of that MHC-segment and its cis-acting control gene. Realizing that telomeric regions are special in many ways, the possibility of sexually dimorphic transcription gradients may be better illustrated by genomic segments which are autosomal and non-telomeric. The fact that a given human chromosomal segment has sexually dimorphic recombination rates suggests the existence of a mechanism similar to (or perhaps identical to) that identified by Shiroishi et al -- especially in view of the fact that when the same chromosomal segment is present in the next generation (but in a member of the opposite sex -- ie her son or his daughter), presumably the recombo rate is reversed in accord with the progeny's XY or XX genotype. Of course, this rationale does not address accessibility issues derived from ES versus differentiated cells and merely conveys a possible similarity between (i) the Shiroishi et al findings and (ii) mechanisms that induce his-cM versus her-cM for the same genomic segment in regard to human chromosomes. Perhaps the accessibility issue is hinted at by considering whether differentiation into a specific cell type erases the trans-acting modifier or whether chromatin condensation merely overrides and renders totally ineffective the trans-modifier, cis-gene effects. Teresa Teresa C. Binstock, Researcher Developmental & Behavioral Neuroanatomy Denver CO USA Teresa.Binstock@uchsc.edu From owner-recombination@net.bio.net Sun Aug 04 23:00:00 1996 Newsgroups: bionet.molbio.recombination Path: biosci!lhc.nlm.nih.gov!nih-csl!NewsWatcher!user From: lichten@helix.nih.gov (Michael Lichten) Subject: Re: Question: A centimorgan (cM) .is how many Kilobases? Message-ID: Sender: postman@alw.nih.gov (AMDS Postmaster) Nntp-Posting-Host: 128.231.218.92 Organization: LB/DCBDC/NCI References: <31FEDC0A.2DF9@odyssee.net> Date: Mon, 5 Aug 1996 18:39:49 GMT Lines: 24 In article <31FEDC0A.2DF9@odyssee.net>, dellaire@ODYSSEE.NET (Graham Dellaire) wrote: > Hello all, > > > I have forgotten the conversion for cM distances in the average > mammalian genome. Does anyone remember the number of kb in a cM? > > Thanks in advance.... > > > this is really bugging me (hehe) > > > Graham Dellaire > McGill University > dellaire@odyssee.net One million nucleotides is about one cM in the human and mouse genomes. -- Michael Lichten lichten@helix.nih.gov From owner-recombination@net.bio.net Mon Aug 05 23:00:00 1996 Newsgroups: bionet.molbio.recombination Path: biosci!agate!newsgate.duke.edu!solaris.cc.vt.edu!newsfeed.internetmci.com!in3.uu.net!nih-csl!NewsWatcher!user From: lichten@helix.nih.gov (Michael Lichten) Subject: Re: Significance of cM sexual dimorphisms (accessibility) Message-ID: Sender: postman@alw.nih.gov (AMDS Postmaster) Nntp-Posting-Host: 128.231.218.92 Organization: LB/DCBDC/NCI References: <199608031758.NAA25405@atlas.odyssee.net> Date: Tue, 6 Aug 1996 19:47:08 GMT Lines: 30 In article <199608031758.NAA25405@atlas.odyssee.net>, dellaire@ODYSSEE.NET ("Dellaire, Graham") wrote: A lot of stuff. I'm sorry, but I think that this discussion has gotten out of control. I agree that the idea of accesibility determining where MEIOTIC recombination occurs is a very appealing one, but, aside from the limited work done on chromatin structure in yeast, do we have ANY experimental evidence? I mean, it's nice to speculate, but let's make sure we distinguish between that and what's real. Maybe I'm being too sensitive here, seeing as that I'm in the thick of this matter, but either there's a lot of literature that I've missed, or irrelevant observations are being drawn into this discussion. As far as I know, it's kindof hard to look at chromatin structure, let alone higher-order chromosome structure, in the male and (especially) the female cells AT THE TIME that recombination is taking place. In fact, I don't think that it's ever been done in females at all. So let's be careful, because someone who doesn't know might read the heading of these articles and get the idea that what's being said in them is actually known to be true. Ciao, Michael Lichten -- Michael Lichten lichten@helix.nih.gov From owner-recombination@net.bio.net Tue Aug 06 23:00:00 1996 Newsgroups: bionet.molbio.recombination Path: biosci!agate!news.ucdavis.edu!info.ucla.edu!nnrp.info.ucla.edu!csulb.edu!news.sgi.com!news.sprintlink.net!news-stk-200.sprintlink.net!news.sprintlink.net!news-stk-11.sprintlink.net!nntp04.primenet.com!news.shkoo.com!nntp.primenet.com!news.cais.net!hunter.premier.net!news.uoregon.edu!arclight.uoregon.edu!usenet.eel.ufl.edu!newsfeed.internetmci.com!mel.hargray.com!news1.sunbelt.net!news.sprintlink.net!news-dc-10.sprintlink.net!news.voicenet.com!news2.noc.netcom.net!noc.netcom.net!netcom.com!bks From: bks@netcom.com (Bradley K. Sherman) Subject: Re: Question: A centimorgan (cM) .is how many Kilobases? Message-ID: Organization: Sunlight + DNA References: <31FEDC0A.2DF9@odyssee.net> Date: Wed, 7 Aug 1996 18:11:18 GMT Lines: 45 Sender: bks@netcom20.netcom.com >I have forgotten the conversion for cM distances in the average >mammalian genome. Does anyone remember the number of kb in a cM? From _Glossary of Genetics_ (Rieger et.al 1991): a measure of genetic distance, i.e. the distance that separates two genes between which there is a 1% chance of genetic recombination. From _A Dictionary of Genetics_ (King & Stansfield 1990): see Morgan unit Morgan unit: a unit for expressing th relative distance between genes on a chromosome. One morgan(M0 equals a crossover value of 100%. A crossover value of 10% is a decimorgan; 1% is a centimorgan. Thus a chromosome with an average of two crossovers per gamete will be twice as long as a chromosome with just one crossover per gamete; completely independent of the number of genes or basepairs physically present. I do not think that there has ever been a survey to see if there is *even a correlation* between length measured in Morgan units and length measured in base pairs. It is my observation that it is often taken as nearly axiomatic that, lacking evidence to the contrary, there is about one-crossover per chromosome per gamete --though I am unclear on the basis for this. So to answer your question with two more questions: 1) What's the average number of crossovers per chromosome in the average mammal? 2) What's the average length of a chromosome in an the average mammal? You can use 1 and 2 to get a conversion, but is the variance too high to make it useful? (Okay, three questions.) --bks From owner-recombination@net.bio.net Wed Aug 07 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET (Graham Dellaire) Newsgroups: bionet.molbio.recombination Subject: Accessibility and MITOTIC recombination.... Date: 7 Aug 1996 21:02:06 -0700 Organization: McGill Div. of Experimental Medicine Lines: 110 Sender: daemon@net.bio.net Distribution: world Message-ID: <320965F6.70F6@odyssee.net> NNTP-Posting-Host: net.bio.net Perhaps I ran so far off topic that it is about time to start a new thread.... Michael L. stated previously... "MEIOTIC recombination occurs is a very appealing one, but, aside from the limited work done on chromatin structure in yeast, do we have ANY experimental evidence? I mean, it's nice to speculate, but let's make sure we distinguish between that and what's real." Reply: Well meiotic recombination is not my field so I won't stretch my neck to far... so I would like to offer some Mitotic references for chromatin accessibility and structure having an impact on recombination. First Indirect... (although how "one" studies chromatin is usually indirect, these are circumstantial) 1. Influence of Chromatin Sturcture on the Induction of DNA DSB's by Ionizing Radiation (Elia and Bradley (1992) Cancer Res. 52, 1580-1586) --- indicating depletion of various histone and non histone fractions from chromatin increases the suseptibility of DNA to DSB's from ionizing radiation. 2.Poly (ADP ribosyl)ation of ploynucleosomes causes relaxation of chromatin structure. (Poirier et al. (1982)PNAS (79) 3423-3427) -----PARP invitro induced relaxation of chromatin reminiscent of H1 extraction. Not much by itself but with the following article which illustrates PARP's relationship to recombination... it does provide one suggested mechanism in addition to the speculation that PARP has a function in DSB repair by perhaps activating DNA ligase II (Althaus et al. 1987, Creissen and Shall 1982) and/or by protecting DNA ends from degredation. 3. Stimulation of intrachromosomal homologous recombinaiton in mammalian cells by an inhibitor of poly(adp-ribosylation) (Waldman A.S. and B.C. Waldman (1991) NAR (19)21:5943-5947) ------------PARP inhibitor 3MB which produces elevated sister chromatid exchange (SCE) reminiscent of Blooms Syndrome (which may also involve DNA metabolism and shudder the thought... chromatin structure and the gene (BLM)involved is thought to be a helicase). As well both gene conversions and crossover events where elevated. Illegitimate integration of transfected DNA is also inhibited by PARP inhibitors (Farzaneh et al. (1988); Waldman and Waldman (1990)). Indicating that illegitimate integration which may proceed primarily via microhomologies and end to end ligation is affected differentially by PARP inhibitors as compared to intrachromosomal homologous recombination events. Warning Speculation: perhaps PARP is involved in remodeling chromatin as it can transfer ADP moieties to HMG and histones perhaps sterically altering their interaction with DNA and other protein factors. More Direct Evidence: 1. Cell Type-Specific Chromatin Structure Determines the Targeting of V(D)J Recombinase Activity In Vivo. (Stanhope-Baker at al. (1996), Cell (85)887-897) ----------these authors demonstrate that both lineage specific and temporally specific gene rearrangements are ordered by accessibility of signal sequences (RSS's) within chromatin to in vitro cleavage. They show that there is both a free nuclear protein factor(s) as well as specific chromatin structure required for B-cell Ig rearrangements vs. T-cell TCR rearrangements. RAG 1 and 2 alone where not sufficient alone. Experiments in fibroblasts that indicated all you needed where the two RAG genes and signal sequences did not show regulation as perhaps both the chromatin component and nuclear protein component where absent in these extrachromosomal assays. (i.e. Accessibility Hypothesis...Yancopoulos and ALt, 1985; Alt et al., 1987) 2. The fragile X site in human hypersensitive to nucleases which might suggest more accessible chromatin arrangement. Furthermore, Fan et al. (1995 MCB 15:1679-88) On the subject of Fragile sites.... Rassool et al. 1991 Show that induction of fragile sites via amphidicolin (inhibitor of DNA polymerase) resulted in increased targeting of a fragile site at 3p14 (4 out of 13)by an exogenous pSV2neo vector in a human/hamster hybrid. 3. Also in yeast... Fan et al. (1995 MCB 15:1679-88) shown that the HIS4 recombination hot spot in yeast (i.e. the generation of breaks) is absent in strains in which the transcription factors Rap1p, Bas1p, and Bas2p cannot bind to the region upstream of HIS4, suggesting once again, the possible involvement of chromosomal structure. Finally a Mieotic recombination reference for yeast.... Meiotic DSBs occur in regions of chromatin that are hypersensitive to nucleases (de Massy et al. EMBO J. (1995) 14:4589-98), suggesting of possible involvements of chromosome structure in recombination. I hope to have been more relevant this time.... sort of hard not to be when you set the topic yourself. Graham P.S. Thanks to fellow D.Leader Terry Chow for a ref or two (wink) From owner-recombination@net.bio.net Thu Aug 08 23:00:00 1996 Path: biosci!agate!howland.erols.net!vixen.cso.uiuc.edu!newsfeed.internetmci.com!csn!nntp-xfer-1.csn.net!csn!nntp-xfer-2.csn.net!tali.UCHSC.edu!essex.UCHSC.edu!binstoct From: Teresa Binstock Newsgroups: bionet.molbio.recombination Subject: Re: Significance of cM sexual dimorphisms (accessibility) Date: Thu, 8 Aug 1996 19:26:53 -0600 Organization: University of Colorado, Health Sciences Center Lines: 24 Message-ID: References: <199608031758.NAA25405@atlas.odyssee.net> NNTP-Posting-Host: essex.uchsc.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: I realize that I am juxtaposing concepts whose summation is not yet demonstrated. However, many studies point in the direction of the possiblity I expressed. As often happens in research, thinking about a possibility necessarily preceeds researching the possibility, preceeds thinking about how a possibility might be researched. Serendipitous, unplanned, accidental scientific discovery is not the only way science proceeds; another route involves pre-conception, possibility thinking, related planning, and specific research methodologies. Furthermore, the Shiroihsi et al findings suggest that the possibilities I outlined/extrapolated are not without at least a teency bit of precedence. Teresa Teresa C. Binstock, Researcher Developmental & Behavioral Neuroanatomy Denver CO USA Teresa.Binstock@uchsc.edu From owner-recombination@net.bio.net Fri Aug 09 23:00:00 1996 Path: biosci!agate!howland.erols.net!vixen.cso.uiuc.edu!newsfeed.internetmci.com!in3.uu.net!noc.nyx.net!tali.UCHSC.edu!essex.UCHSC.edu!binstoct From: Teresa Binstock Newsgroups: bionet.molbio.recombination Subject: New Shiroishi et al Date: Sat, 10 Aug 1996 10:01:19 -0600 Organization: University of Colorado, Health Sciences Center Lines: 4 Message-ID: References: <199608031758.NAA25405@atlas.odyssee.net> NNTP-Posting-Host: essex.uchsc.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: au: Mizuno K et al (including Shiroishi) so: Mammalian Genome 7.490-6 1996 ti: Molecular analysis of a recominational hotspot adjacent to Lmp2 in the mouse MHC: fine location and chromatin structure. From owner-recombination@net.bio.net Wed Aug 14 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET (Graham Dellaire) Newsgroups: bionet.molbio.recombination Subject: New at Experimental Medicine Jobs Listings!!! (Job submission form) Date: 14 Aug 1996 17:54:52 -0700 Organization: McGill Div. of Experimental Medicine Lines: 173 Sender: daemon@net.bio.net Distribution: world Message-ID: <321274A3.2879@odyssee.net> NNTP-Posting-Host: net.bio.net *******New at Experimental Medicine Job Listings***** Job submission form! http://www.medcor.mcgill.ca/EXPMED/DOCS/jobform.html We have set up a form for submission of your job listings. Using any forms capable browser you can submit your listing without the need of an e-mail account! Current listing of jobs to date at EXPMED JOB LISTINGS.... http://www.medcor.mcgill.ca/EXPMED/DOCS/jobs.html Government 1.Environment Professionals, OFFICE OF THE AUDITOR GENERAL Deadline August 14/96 2.Population Management Biologist (Edmonton, Alberta) Deadline August 2/96 3.Mycologist (Victoria, B.C.) Deadline August 12/96 4.Atmospheric Aerosol Chemist, to study climate at Environment Canada Deadline August 8/96 5.Research Biologist, Dept. of Fisheries and Oceans (Nanaimo, B.C.) Deadline July 30/96 6.Insect Pathologist (Forestry) (Victoria, B.C.) Deadline August 1st/96 Montreal Area 1.McGill General Jobs in Biomedical Engineering 2 Positions available in the laboratory of Dr. B. Leyland-Jones Posted June 25th/96 1 to 2 Masters positions and 1 Post-Doc Clinical Trial Research Group Bioethics Research Unit (Law, Epidemiology, Experimental Medicine or Faculty of Medicine) 2.IRCM HEMOPOIESIS CANCER AND DEVELOPMENT GROUP Molecular Genetics; Differentiation and Development; Oncology; Immunology; and Gene Therapy (post doctoral positions available) Posted July 3rd/96 1 Position available immediately in the laboratory of Dr. Guy Sauvageau POSITION FILLED 3.Lady Davis Institute 1 Position (Ph.D.) in the laboratory of Dr. Prem Ponka Posted April 9/96 4.Royal Victoria Hospital 1 Position (Ph.D.) in the laboratory of Dr. Geoffrey Hendy Posted March 20/96 1 Position (Ph.D.) in the laboratory of Dr. David Goltzman Posted May 21/96 5.Montreal General Hospital 1 Position (Post-Doc) in the laboratory of Dr. Guy A. Rouleau Posted May 4/96 Ontario 1.Positions at Waterloo University in Biology 2.2 tenure track Positions University of Toronto Depts. of Biochemistry & Medical Genetics and Microbiology DEADLINE Sept. 1/96 3.3 tenure track Positions University of Toronto Dept. of Medical Genetics and Microbiology DEADLINE August 15/96 4.Samuel Lunenfeld Post-Doctoral Fellowship Samuel Lunenfeld Research Institute, Mount Sinai Hospital Posted April 26th/96 Manitoba 1.Positions at the University of Manitoba in Medical Microbiology Alberta 1.Positions at the University of Alberta Positions in Biological Sciences 2.Several Positions at IntelliGene Expressions, Inc. (Edmonton Alberta) Posted July 3rd/96 British Columbia 1.2 positions: Assistant Professor and Associate/full Professor at the Biomedical Research Center in Vancouver (UBC) Deadline:August 31, 1996 2.1 position Catalyx Group Biopharmaceuticals Posted June 16th/96 3.1 position University of BC Dept. of Microbiology and Immunology Research Associate Posted July 3rd/96 4.1 position University of BC Microbiology one year research position Posted July 3rd/96 Outside of Canada 1. United States 1.Opportunities at the National Institutes for Health, Bethesda Maryland +140 postings for postdoctoral positions online, more than 30 clinical training programs and all listings support immediate online application. 2.1 Position: in the laboratory of Dr. Moshe Sadofsky at MCG-IMMAG (Augusta, GA) Available Immediately 3.Positions at Clontech 4.1 Position as Chair of Dept.'s of Biochemistry and Microbiology University of North Texas Posted April 4th/96 5.1 Position Director of Biotechnology Facility Indiana University (Biochemistry & Molecular Biology) Posted May 22nd/96 6.1 Position Professor and Chair Medical College of Ohio (Toledo, Ohio) Posted May 22nd/96 2. Europe Great Britain 1.Positions at Cambridge University Dept. of Biochemistry Dept. of Pathology 2.Positions at the Institute of Biomedical and Life Sciences at the University of Glasgow, Scotland Look under "posts available". 3.Positions at Imperial College in the Dept. of Biochemistry 4.Vacancies at the Institute of Cancer Research London 5.Wellcome Foundation Telnet server offering Post-Doctoral and other listings Log-on with the password "wisdom" 3. Australia 1.Positions at the University of Queensland 2.Queensland Pharmaceutical Research Institute From owner-recombination@net.bio.net Sat Aug 17 23:00:00 1996 Path: biosci!internet!biosci!not-for-mail From: biohelp (BIOSCI Administrator) Newsgroups: bionet.molbio.recombination Subject: BIOSCI/bionet miniFAQ & Fundraiser Date: 18 Aug 1996 02:00:07 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 239 Sender: daemon@net.bio.net Distribution: world Message-ID: <199608180900.CAA16621@net.bio.net> NNTP-Posting-Host: net.bio.net (LAST REVISION: 30-JUL-95) This BIOSCI "miniFAQ" is designed to answer the questions that come up the *most frequently*. The main BIOSCI FAQ (Frequently Asked Questions) is accessible on the World Wide Web at URL http://www.bio.net/. If you can not find an answer to your question in this or other documentation, the BIOSCI technical support staff answers e-mail queries sent to biosci-help@net.bio.net We can only answer questions about the use of the newsgroups and mailing lists. We unfortunately do not have the staff to do Internet information searches or answer scientific questions. Please post those to the appropriate BIOSCI/bionet newsgroups. Contents: -------- 0) BIOSCI NEEDS YOUR SUPPORT!! 1) Using the WWW to access the BIOSCI/bionet newsgroups. 2) What to do about "spams," i.e., junk mail, ads, etc. 3) Examples of subscribing and unsubscribing to the mailing lists. 4) The BIOSCI user address and research interest directory. 0) BIOSCI NEEDS YOUR SUPPORT!! ------------------------------ BIOSCI's government funding has been expended, and we are now operating solely from advertising revenue that we have raised from our Web site at http://www.bio.net/. We need just a few minutes of your time to help us serve you. You can do two important things which will take very little time for you individually and will immensely help us continue to help you. First, please use our WWW system at http://www.bio.net/ to access the archives. You can post or reply to messages via your Web browser as described in item #1 below. Your usage helps attract sponsors. If you contact any of our sponsors, please be sure to thank them for supporting BIOSCI. It is critical for them to get this feedback if they are to continue their sponsorship for the long term. Second, if you work for a company or organization that provides products or services of interest to the biology community, please pass this message on to your marketing or marketing communications department or other appropriate group. Please ask them to help support BIOSCI by sponsoring our Web site and explain the uses and benefits of the system to the biology community. If they are interested, they can then contact us for further information at our tech support address, biosci-help@net.bio.net. 1) Using the WWW to access the BIOSCI/bionet newsgroups. -------------------------------------------------------- As of 10 December 1995, all BIOSCI/bionet full newsgroups are accessible through the World Wide Web (WWW) at URL http://www.bio.net. One can read and reply publicly or privately to both recent postings and archived messages through one's Web browser if it is configured properly to send e-mail. Each newsgroup is equipped with its own WAIS index. The main BIOSCI home page also has access to the BIO-JOURNALS Table of Contents database WAIS index and the BIOSCI user address database described in another item further below. 2) What to do about "spams," i.e., junk mail, ads, etc. ------------------------------------------------------- BIOSCI is a set of parallel USENET newsgroups (the "bionet" groups), mailing lists, and a hypermail archive at URL http://www.bio.net/. The same postings are distributed on all media (except for a small number of mailing-list-only groups at net.bio.net). Unfortunately it is becoming a despicable practice on the Internet (by a few people out to make a fast buck) to do automated mass postings to thousands of newsgroups and mailing lists. These attempts to grab free advertising are refered to as "spams" in the usual, somewhat boneheaded, net terminology. USENET is more susceptible to this practice, and many spams originate on the USENET groups and then are passed on to the mailing lists. However, spammers also get lists of mailing addresses and hit these too, so neither medium is immune. What should you do personally if you get junk mail? --------------------------------------------------- Just delete it and move on without reading it further. Filing a protest is becoming increasingly useless because spammers are often disguising the addresses where the messages are sent from. Unless you really understand Internet mail systems, your attempt at protest by sending replies to the message will often end up being sent to the address of an innocent person that the spammer is victimizing. What can BIOSCI/bionet do to protect its newsgroups? ---------------------------------------------------- The only solution currently available is to moderate the newsgroup. If this newsgroup is already moderated, then you are in good shape. Moderation protects the USENET distribution from about 95% of the spams that are being sent to date and protects the mailing lists completely. Moderation means, however, that someone has to take the time to review each message before it goes out. We have set up software here that simply allows the moderator to forward to an address at net.bio.net messages that (s)he wishes to have distributed. This takes no more time than that needed to read the message and pass it on, say about 1 min. per message. Most newsgroups currently have a discussion leader who is responsible for their newsgroup. The discussions leaders and their e-mail addresses are listed in the BIOSCI Information Sheet which is available on the Web at http://www.bio.net/. If a newsgroup is being hit with too many junk postings, please contact the discussion leader for that group and see if there is interest in moderating the group. Please do not assume that by simply posting a complaint to the newsgroup itself, anyone on the BIOSCI staff will act on your complaint. With close to 100 newsgroups to run, the BIOSCI staff has to rely on the discussion leaders of each newsgroup to report problems directly to us at biosci-help@net.bio.net. We will moderate any of our newsgroups if the discussion leader tells us that the readership of the group wishes to do so and if a moderator is willing to do the work. For most BIOSCI/bionet groups, this entails only a few minutes of work each day. Moderating a newsgroup will resolve probably 95% of the junk postings on the USENET distribution. Unfortunately there are easy ways for determined spammers to override the moderation mechanism on USENET, but we can protect our e-mail subscribers from unwanted postings if the newsgroup is moderated. You can also access our newsgroups over the WWW at URL http://www.bio.net. While this Web interface will not stop spammers from trying to post to the groups, this will give you yet another way, besides using USENET news, to keep the junk out of your personal mail files. For those of you with local USENET news systems, the Web interface will also give you faster access to new newsgroups and recent postings. 3) Examples of subscribing and unsubscribing to the mailing lists. ------------------------------------------------------------------ PLEASE NOTE: The BIOSCI management does NOT act on subscription/unsubscription requests that are posted improperly to the newsgroups and mailing lists. People who do this only bother everyone on the lists to no avail. Please be sure to follow the proper procedures below. Gory details are in the BIOSCI Information sheets on the Web at http://www.bio.net. Below we give an example utilizing the METHODS-AND-REAGENTS list at both of our two BIOSCI sites: Users in the Americas and Pacific Rim countries who use the BIOSCI ------------------------------------------------------------------ node at computer net.bio.net: ---------------------------- A) Determine the "listname" which is the <=8 character mail address ^^^^^^^^^^^^^ for the group. These can be found in the BIOSCI Info. Sheet. For the METHODS-AND-REAGENTS group the mailing address is methods@net.bio.net. The listname is the portion of the address to the left of the @ sign, i.e., "methods". The listname is used with the "subscribe" and "unsubscribe" commands illustrated below. B) Mail all commands in the body of a mail message addressed to biosci-server@net.bio.net. Do NOT send commands to the newsgroup posting addresses! Leave the Subject: line blank, any text on it will be ignored. C) In the body of your message put one or more of the following commands with an "end" command on the last line, e.g., subscribe methods unsubscribe methods end Do NOT put your e-mail address or other text on these lines. The server only allows you to cancel your subscription if the address on your mail header matches the address on our mailing list. Please ask for help at biosci-help@net.bio.net if your address has changed, e.g., if you know you are on the list but the server tells you that you are not a member. Users in Europe, Africa, and Central Asia who use the BIOSCI node at -------------------------------------------------------------------- computer daresbury.ac.uk (also known as dl.ac.uk): ------------------------------------------------- To subscribe and unsubscribe to/from the BIOSCI lists, you need to specify the full USENET newsgroup name with "bionet-news." prepended. The USENET newsgroup names are listed in the BIOSCI Information sheet on the Web at http://www.bio.net/. For the METHODS-AND-REAGENTS list the USENET newsgroup name is bionet.molbio.methds-reagnts, thus the appropriate commands are sub bionet-news.bionet.molbio.methds-reagnts unsub bionet-news.bionet.molbio.methds-reagnts These commands are included in a message addressed to mxt@dl.ac.uk, NOT to the newsgroup mailing addresses. As usual, include the text in the body of the message as text on the Subject: line is ignored. To unsubscribe from all the lists at the UK node, use unsub bionet-news Please note that if the address in the list is different than the one in your mail message header, you will not be able to unsubscribe by this method. If you have problems, please mail biosci@daresbury.ac.uk. 4) The BIOSCI user address and research interest directory. ----------------------------------------------------------- Please take this opportunity to add your name, address, and research interest information to the BIOSCI User Address Database if you have not already done so. You can fill out the address form directly through our Web page at URL http://www.bio.net/adrform.html. The address database is reindexed nightly for WWW access (the URL is http://www.bio.net/). If you are not directly on the Internet but can reach it by e-mail, please use our waismail server to access the user directory. waismail use is described above. You can also request a user address form by e-mail from biosci-help@net.bio.net. Please check your database entry from time-to-time to see if your address information is still up-to-date. Because of our limited personnel resources, we ask that you resubmit a *complete* form to revise your entry; we only replace complete entries and do not have resources to edit old forms. Sincerely, Dave Kristofferson BIOSCI/bionet Manager biosci-help@net.bio.net From owner-recombination@net.bio.net Sun Aug 25 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET (Graham Dellaire) Newsgroups: bionet.molbio.recombination Subject: Crossovers, Chiasmata and chromosomes....are they required for Mitosis???? Date: 25 Aug 1996 20:43:38 -0700 Organization: McGill Div. of Experimental Medicine Lines: 60 Sender: daemon@net.bio.net Distribution: world Message-ID: <32211CD0.1129@odyssee.net> NNTP-Posting-Host: net.bio.net *****Look Ma, no chromosomes!***** That was the bi-line for a introduction (by Jeremy Hyams) to two "seminal" articles in Nature this past week (August 1,1996): (1)Heald et al. 1996, Nature Vol. 382 page 420 and (2)Zhang and Nicklas 1996, Nature Vol. 382 page 466 The work in these articles showed that in two different systems, Xenopus(1) and grasshopper(2), chromosomes could be removed and an apparently normal spindle apparatus formed and mitosis (including anaphase and cytokinesis) could occur in there absence. In the first(1) paper Xenopus egg extracts and magnetic beads coated with chromatin where combined in vitro. A bipolar spindle apparatus formed in the absence of centromeric sequences. Thus in the absence of pulling forces from kinetochores a bipolar symmetrical array of microtubles could form. The authors then suggest that the true function of kinetochores whould be to segregate chromsomes at anaphase. The second paper (2) a spindle apparatus was allowed to form in grasshopper spermatocytes. At this time the chromosomes where removed by micromanipulation. The de-chromatized cells then proceeded through mitosis including anaphase and cytokinesis! So much for the assertions of the first authors about anaphase and kinetochores!!!? WOW! That was my first reaction. What about all the models of x-overs being required for disjunction of chromosomes? What about the idea of kinetochore motors, bound at the centromere, helping chromosome move to their opposite poles in mitosis from anaphase on? Another challenge to X-overs and proper disjunction occurs in Drosophila where achiasmatic chromosomes segregate almost faultlessly. Recently it has been demonstrated that this phenomenon may rely on the association of heterochromatin between the achiasmatic pair (Dernburg et al. 1996 Cell (last issue)). So why do we seem to require X-overs for proper disjunction and segregatin of chromosomes in human and murine systems? (in yeast too perhaps, but not being my field I would ask that this be clarified by someone in the field). Comments please! Perplexed and hungry for debate, G. Dellaire Experimental Medicine McGill University dellaire@odyssee.net From owner-recombination@net.bio.net Mon Aug 26 23:00:00 1996 Path: biosci!ODYSSEE.NET!dellaire From: dellaire@ODYSSEE.NET (Graham Dellaire) Newsgroups: bionet.molbio.recombination Subject: New Jobs listed at EXPMED JOB Listings!!!!August 27th ,1996 Date: 27 Aug 1996 05:51:58 -0700 Organization: McGill Div. of Experimental Medicine Lines: 46 Sender: daemon@net.bio.net Distribution: world Message-ID: <3222EEC3.749C@odyssee.net> NNTP-Posting-Host: net.bio.net New jobs listings at EXPMED JOB LISTINGS http://www.medcor.mcgill.ca/EXPMED/DOCS/jobs.html 1)Job Openinigs in Biomedical Engineering Biomedical Engineer for the Division of Urology Ph.D. Student in Computer-Based Toxicology (see Canada/Montreal Area/McGill General) 2)1 to 2 Masters positions and 1 Post-Doc Clinical Trial Research Group Bioethics Research Unit (Law, Epidemiology, Experimental Medicine or Faculty of Medicine) 3)Ph.D. studies in Signal transduction in kidney cells in immunological renal diseases and in renal development(see Canada/Montreal Area/Royal Victoria Hospital 1 position (Ph.D.) in the laboratory of Dr. A.V. Cybulsky Posted August 22/96) 4)The role of the MyoD-family of transcription factors in the formation and function of myogenic stem cells in skeletal muscle (see Canada/Ontario-- 1 post-doc position in the laboratory of Dr. Rudnicki at MOBIX (McMaster University, Hamilton, Ontario) AVAILABLE IMMEDIATELY (NIH FUNDED)) 5) Function and molecular regulation of the new mammalian hormone: Stanniocalcin. and Transcriptional regulation of cell-specific gene expression in the endometrium (see Canda/Ontario--- 2 Positions in the laboratory of Dr. G. Dimattia (London Regional Cancer Centre, London, Ontario)) 1 Ph..D and 1 Post-Doc (Available Immediately) . Hope you find something you like and keep looking. The perfect post-doc is probably right around the next web page. G. Dellaire Webmaster EXPMED HOME PAGE McGill University From owner-recombination@net.bio.net Wed Aug 28 23:00:00 1996 Newsgroups: bionet.molbio.recombination Path: biosci!daresbury!sunsite.doc.ic.ac.uk!agate!newsxfer2.itd.umich.edu!gatech!nntp0.mindspring.com!news.mindspring.com!newspump.sol.net!nntp04.primenet.com!nntp.primenet.com!howland.erols.net!cam-news-hub1.bbnplanet.com!uunet!in2.uu.net!nih-csl!NewsWatcher!user From: lichten@helix.nih.gov (Michael Lichten) Subject: Re: Crossovers, Chiasmata and chromosomes....are they required for Mitosis???? Message-ID: Sender: postman@alw.nih.gov (AMDS Postmaster) Nntp-Posting-Host: 128.231.218.92 Organization: LB/DCBDC/NCI References: <32211CD0.1129@odyssee.net> Date: Thu, 29 Aug 1996 19:12:08 GMT Lines: 84 In article <32211CD0.1129@odyssee.net>, dellaire@ODYSSEE.NET (Graham Dellaire) wrote regarding: > (1)Heald et al. 1996, Nature Vol. 382 page 420 > and > (2)Zhang and Nicklas 1996, Nature Vol. 382 page 466 > > > The work in these articles showed that in two different systems, > Xenopus(1) and grasshopper(2), chromosomes could be removed and an > apparently normal spindle apparatus formed and mitosis (including > anaphase and cytokinesis) could occur in there absence. In the first(1) > paper Xenopus egg extracts and magnetic beads coated with chromatin > where combined in vitro. A bipolar spindle apparatus formed in the > absence of centromeric sequences. Thus in the absence of pulling forces > from kinetochores a bipolar symmetrical array of microtubles could > form. The authors then suggest that the true function of kinetochores > whould be to segregate chromsomes at anaphase. > The second paper (2) a spindle apparatus was allowed to form in > grasshopper spermatocytes. At this time the chromosomes where removed > by micromanipulation. The de-chromatized cells then proceeded through > mitosis including anaphase and cytokinesis! So much for the assertions > of the first authors about anaphase and kinetochores!!!? In the Zhang & Nicklaus paper, chromosomes are removed AFTER the spindle apparatus has formed. The Nicklaus and Gorbsky groups have already shown that, in this system (grasshoper spermatocytes) kinetochore that are not under tension inhibit anaphase. It therefore isn't too surprising that once Zhang & Nicklaus removed the chromosomes, the cells went through anaphase. Heald et al suggest that the function of kinetochores is to segregate chromosomes at anaphase--in other words, as the physical connection between chromosomes and the spindle apparatus that lets chromosomes get pulled to opposite poles. I don't see what there is in the Zhang & Nicklaus paper that contradicts this. After all, the mitotic spindle apparatus didn't evolve in the absence of chromosomes, so removing the chromosomes creates a slightly artificial (but informative) situation. > ... > > Another challenge to X-overs and proper disjunction occurs in Drosophila > where achiasmatic chromosomes segregate almost faultlessly. Recently it > has been demonstrated that this phenomenon may rely on the association > of heterochromatin between the achiasmatic pair (Dernburg et al. 1996 > Cell (last issue)). How about Drosophila males, where there's NO recombination at all? > > So why do we seem to require X-overs for proper disjunction and > segregatin of chromosomes in human and murine systems? (in yeast too > perhaps, but not being my field I would ask that this be clarified by > someone in the field). > Crossovers are the endproduct of a homology-based pairing mechanism, not the pairing mechanism itself. If you fail to pair, you don't get crossovers. But to say that you require crossovers for proper disjunction and segregation is to miss the point. 1. Drosophila has 4 chromosomes. You could imagine that with that few, one could evolve four separate site-specific pairing systems that would function in male meiosis. For critters with more chromosomes, this would be impossible. 2. There ARE xover defective meiotic mutants in Drosophila that fail to disjoin proper--as if the system can handle a pair of achiasmate chromosomes but not a whole genome's worth. 3. Crossovers are needed to provide the physical connection between homologs, which in turn provides tension (remember tension? see above), which in turn prevents kinetochores from signalling, which in turn allows anaphase I to proceed. In other words, the cell uses the tension provided by crossovers as a signal that, back at step 1, it paired chromosomes properly. If a pair of homologs failed to pair, then they wouldn't cross-over, wouldn't create tension, and their kinetochores would still generate the anaphase-inhibiting signal. Hope this clarifies rather than muddies the issue. -- Michael Lichten lichten@helix.nih.gov