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Male-driven evolution of DNA sequences
mONITOR Male-driven evolution of DNA sequences L.D. SHIMMIN, B.H-J. CHANG AND W-H. Li
Nature 362, 745-747 It is generally accepted that DNA sequences are evolving faster in the germline of human males than in the human female germline, because the germ-line cells of males divide many more times per generation than those of females and thus accumulate more replication-dependent mutations. The generation-time effect also has implications for relative mutation rates in different organisms, since short-lived organisms tend to have higher rates of germ cell division (divisions per
Two types of pole cells are present in the Drosophila embryo, one with and one without splicing activity for the third P.element intron S. KOBAYASHI, T. KITAMURA,H. SASAKI AND M. OKADA
Development 117, 885--893 High-level transposition of the Drosophila P element only occurs in germ-line cells, because only in those cells is the third intron spliced out of the P element, enabling production of functional transposase. But what is the intrinsic function of this germ-linespecific splicing activity, which must presumably have been there long before its fairly recent hijacking by P? Kobayashi et al. show that the activity is a marker for the small fraction of
Signals from the notochord and floor plate regulate the region.specific expression of two Pax genes in the developing spinal cord M. GOULDING, A. LUMSDEN AND P. GRUSS
Development 117, 1001-1016 The expression patterns of a number of paired box (Pax) genes during embryogenesis seem to be related to development of the nervous system. In particular, in the mouse, Pax-3, Pax-6 and Pax-7 are expressed in dorsoventrally restricted regions of the developing spinal cord. This seems likely to be significant, since the differentiation of specific cell types (such as motor neurons, or neural crest cells) correlates with their dorsoventral position in the spinal cord. The notochord is known to play a role in ventralizing the neural
unit time) than longer-living ones. The magnitude of a m, the ratio of male:female mutation rates, is important, because it is in indicator of how significant the generation-time effect is. a m --- (M + N)/(F + N), where M is the replication-dependent mutation rate in males, F is the replication-dependent mutation rate in females, and N is the non-replicationdependent mutation rate (which should be equal in males and females). If a m is very large, it implies that M>>F (i.e. a large effect of generation time), whereas if eam approaches 1, it implies that N is a much larger component than either M or F. Previous work suggested that a m is extremely
large, but those studies generally compared mutation rates for X-linked genes with rates for nonhomologous autosomal genes. The conclusions are questioned by Shimmin et aL, who have compared point mutation rates for an intron of the homologous Xlinked and Y-linked zinc finger protein genes ZFX and ZFY The value they derive for cx,~ has a fairly wide margin of error, but is definitely much closer to 1 than were previous estimates. The implication is that non-replication-dependent mutational processes, such as methylation and oxidative damage, may have a more important influence on sequence evolution than was thought.
pole cells that penetrate the embryonic gonad and go on to produce germ cells, and suggest that the splicing is somehow involved in the differentiation process. They followed the splicing activity during early development by visualizing 13-galactosidase production from a construct consisting of a P element with a heat shock promoter and with the lacZ gene inserted in frame downstream of the third intron. Embyos containing this construct were heat treated at 0-15 hours after egg laying (AEL), incubated for one hour at normal temperature, then stained with X-Gal. Maximal ability to splice the third intron was observed at 5--6 hours &EL, but double staining with X-Gal and with antibody to the vasa protein - a marker for pole cells -
showed that only a small fraction of the pole cells had the splicing activity. If embryos were heat shocked at 5-6 hours AEL and then left to develop for another eight hours before staining, all the X-Gal positive pole cells were found in the gonad, and all those that remained outside the gonad (subsequently to degenerate) were X-Gal negative. It used to be assumed that all pole cells were equivalent and mere chance dictated which pole cells ended up in the gonad. From the work of Kobayashi et al. it is clear that in fact pole cells are a heterogeneous bunch, and only those that make the splice, make the gonad. Exactly how the splicing activity is involved in germ cell differentiation remains to be discovered. /~
tube. It induces formation of the floor plate, which lies along the ventral midline of the neural tube and produces signals that direct development of motor neurons. Goulding et al. have used the chick to study how expression of the Pax genes becomes dorsoventrally restricted, since development of the spinal cord is easier to observe than in the mouse, and techniques for surgical manipulation of the chick embryo are well advanced. The chick homologues of Pax-3 and Pax-6 were cloned and characterized, and their expression patterns studied in early embryos. Pax-3 and Pax-6 expression became dorsovemrally restricted after neural tube closure (Pax-3 to the dorsal half and Pax-6 to the mid-lateral region of the spinal cord), but the expression patterns
were rapidly and markedly disrupted if the notochord was removed or if a second notochord was ectopically implanted. The changes in Pax gene expression were accompanied by changes in the differentiation patterns of motor neurons. The new expression patterns that were observed suggested that signals from the notochord normally repress Pax-3 and Pax-6 expression in the nearby ventral neuroepithelium, and that these effects on Pax gene expression are an early step in the pathway by which the notochord affects patterning of the spinal cord. The notochord may not be the only source of patterning signals; it seems likely that dorsal structures such as the roof plate may also be involved in setting up the final expression patterns of genes such as Pax-3 and Pax-6.
TIG JULY1993 VOL.9 NO. 7
~-33
Nature 362, 745-747 It is generally accepted that DNA sequences are evolving faster in the germline of human males than in the human female germline, because the germ-line cells of males divide many more times per generation than those of females and thus accumulate more replication-dependent mutations. The generation-time effect also has implications for relative mutation rates in different organisms, since short-lived organisms tend to have higher rates of germ cell division (divisions per
Two types of pole cells are present in the Drosophila embryo, one with and one without splicing activity for the third P.element intron S. KOBAYASHI, T. KITAMURA,H. SASAKI AND M. OKADA
Development 117, 885--893 High-level transposition of the Drosophila P element only occurs in germ-line cells, because only in those cells is the third intron spliced out of the P element, enabling production of functional transposase. But what is the intrinsic function of this germ-linespecific splicing activity, which must presumably have been there long before its fairly recent hijacking by P? Kobayashi et al. show that the activity is a marker for the small fraction of
Signals from the notochord and floor plate regulate the region.specific expression of two Pax genes in the developing spinal cord M. GOULDING, A. LUMSDEN AND P. GRUSS
Development 117, 1001-1016 The expression patterns of a number of paired box (Pax) genes during embryogenesis seem to be related to development of the nervous system. In particular, in the mouse, Pax-3, Pax-6 and Pax-7 are expressed in dorsoventrally restricted regions of the developing spinal cord. This seems likely to be significant, since the differentiation of specific cell types (such as motor neurons, or neural crest cells) correlates with their dorsoventral position in the spinal cord. The notochord is known to play a role in ventralizing the neural
unit time) than longer-living ones. The magnitude of a m, the ratio of male:female mutation rates, is important, because it is in indicator of how significant the generation-time effect is. a m --- (M + N)/(F + N), where M is the replication-dependent mutation rate in males, F is the replication-dependent mutation rate in females, and N is the non-replicationdependent mutation rate (which should be equal in males and females). If a m is very large, it implies that M>>F (i.e. a large effect of generation time), whereas if eam approaches 1, it implies that N is a much larger component than either M or F. Previous work suggested that a m is extremely
large, but those studies generally compared mutation rates for X-linked genes with rates for nonhomologous autosomal genes. The conclusions are questioned by Shimmin et aL, who have compared point mutation rates for an intron of the homologous Xlinked and Y-linked zinc finger protein genes ZFX and ZFY The value they derive for cx,~ has a fairly wide margin of error, but is definitely much closer to 1 than were previous estimates. The implication is that non-replication-dependent mutational processes, such as methylation and oxidative damage, may have a more important influence on sequence evolution than was thought.
pole cells that penetrate the embryonic gonad and go on to produce germ cells, and suggest that the splicing is somehow involved in the differentiation process. They followed the splicing activity during early development by visualizing 13-galactosidase production from a construct consisting of a P element with a heat shock promoter and with the lacZ gene inserted in frame downstream of the third intron. Embyos containing this construct were heat treated at 0-15 hours after egg laying (AEL), incubated for one hour at normal temperature, then stained with X-Gal. Maximal ability to splice the third intron was observed at 5--6 hours &EL, but double staining with X-Gal and with antibody to the vasa protein - a marker for pole cells -
showed that only a small fraction of the pole cells had the splicing activity. If embryos were heat shocked at 5-6 hours AEL and then left to develop for another eight hours before staining, all the X-Gal positive pole cells were found in the gonad, and all those that remained outside the gonad (subsequently to degenerate) were X-Gal negative. It used to be assumed that all pole cells were equivalent and mere chance dictated which pole cells ended up in the gonad. From the work of Kobayashi et al. it is clear that in fact pole cells are a heterogeneous bunch, and only those that make the splice, make the gonad. Exactly how the splicing activity is involved in germ cell differentiation remains to be discovered. /~
tube. It induces formation of the floor plate, which lies along the ventral midline of the neural tube and produces signals that direct development of motor neurons. Goulding et al. have used the chick to study how expression of the Pax genes becomes dorsoventrally restricted, since development of the spinal cord is easier to observe than in the mouse, and techniques for surgical manipulation of the chick embryo are well advanced. The chick homologues of Pax-3 and Pax-6 were cloned and characterized, and their expression patterns studied in early embryos. Pax-3 and Pax-6 expression became dorsovemrally restricted after neural tube closure (Pax-3 to the dorsal half and Pax-6 to the mid-lateral region of the spinal cord), but the expression patterns
were rapidly and markedly disrupted if the notochord was removed or if a second notochord was ectopically implanted. The changes in Pax gene expression were accompanied by changes in the differentiation patterns of motor neurons. The new expression patterns that were observed suggested that signals from the notochord normally repress Pax-3 and Pax-6 expression in the nearby ventral neuroepithelium, and that these effects on Pax gene expression are an early step in the pathway by which the notochord affects patterning of the spinal cord. The notochord may not be the only source of patterning signals; it seems likely that dorsal structures such as the roof plate may also be involved in setting up the final expression patterns of genes such as Pax-3 and Pax-6.
TIG JULY1993 VOL.9 NO. 7
~-33