Evolution of chromosome Y in primates

We have investigated, by fluorescence in situ hybridization (FISH), the cytogenetic evolution of the Y chromosome in primates using 17 yeast artificial chromosomes, representative of the Y-specific euchromatic region of the human chromosome Y. The FISH experiments were performed on great apes (Homo sapiens, Pan troglodytes, Gorilla gorilla and Pongo pygmaeus pygmaeus), and on two Old World monkeys species as an outgroup (Cercopitecidae Macaca fascicularis and Papio anubis). The results showed that this peculiar chromosome has undergone rapid and unconstrained evolution both in sequence content and organization. Received: 16 January 1998; in revised form: 29 May 1998 / Accepted: 24 June 1998     

Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes

Studies of Y chromosome evolution often emphasize gene loss, but this loss has been counterbalanced by addition of new genes. The DAZ genes, which are critical to human spermatogenesis, were acquired by the Y chromosome in the ancestor of Old World monkeys and apes. We and our colleagues recently sequenced the rhesus macaque Y chromosome, and comparison of this sequence to human and chimpanzee enables us to reconstruct much of the evolutionary history of DAZ. We report that DAZ arrived on the Y chromosome about 38 million years ago via the transposition of at least 1.1 megabases of autosomal DNA. This transposition also brought five additional genes to the Y chromosome, but all five genes were subsequently lost through mutation or deletion. As the only surviving gene, DAZ experienced extensive restructuring, including intragenic amplification and gene duplication, and has been the target of positive selection in the chimpanzee lineage. Editor's suggested further reading in BioEssays Should Y stay or should Y go: The evolution of non‐recombining sex chromosomes Abstract     

A cytogenetic analysis of X- ray induced male steriles on the Y chromosome of Drosophila melanogaster

A total of 1020 B ^s Yy ⁺chromosomes was screened for the induction of male sterile mutations by X irradiation. The 29 recovered mutations were analyzed by genetic complementation and the metaphase chromosomes stained with Hoechst 33258 and observed with fluorescence microscopy. The cytological and genetic maps derived from this analysis were compared to similar maps of the Y chromosome mutations isolated in an earlier study (Brosseau, 1960). Unlike the previous work we have identified only 6 male fertility loci (2 on the short arm, 4 on the long arm) on the Y chromosome. These loci are distributed along the length of the long arm and are likely to reside at two separate sites on the short arm. There is no apparent clustering of these fertility factors in this heterochromatic chromosome. The deletions obtained in this study were observed to be unstable and the nature of this instability was investigated. The original Y chromosome was marked at both telomeres with normally X-linked genes. The loss of one or the other of these markers was accompanied in many cases by the concomitant loss of large segments of Y chromosome material. The possible mechanism of this loss is discussed.Author to whom correspondence should be sent     

The role of chromosomal rearrangements in the evolution of <Emphasis Type="Italic">Silene latifolia</Emphasis> sex chromosomes

Silene latifolia is a model plant for studies of the early steps of sex chromosome evolution. In comparison to mammalian sex chromosomes that evolved 300 mya, sex chromosomes of S. latifolia appeared approximately 20 mya. Here, we combine results from physical mapping of sex-linked genes using polymerase chain reaction on microdissected arms of the S. latifolia X chromosome, and fluorescence in situ hybridization analysis of a new cytogenetic marker, Silene tandem repeat accumulated on the Y chromosome. The data are interpreted in the light of current genetic linkage maps of the X chromosome and a physical map of the Y chromosome. Our results identify the position of the centromere relative to the mapped genes on the X chromosome. We suggest that the evolution of the S. latifolia Y chromosome has been accompanied by at least one paracentric and one pericentric inversion. These results indicate that large chromosomal rearrangements have played an important role in Y chromosome evolution in S. latifolia and that chromosomal rearrangements are an integral part of sex chromosome evolution.     

The Drosophila simulans Y chromosome interacts with the autosomes to influence male fitness

The Y chromosome should degenerate because it cannot recombine. However, male‐limited transmission increases selection efficiency for male‐benefit alleles on the Y, and therefore, Y chromosomes should contribute significantly to variation in male fitness. This means that although the Drosophila Y chromosome is small and gene‐poor, Y‐linked genes are vital for male fertility in Drosophila melanogaster and the Y chromosome has large male fitness effects. It is unclear whether the same pattern is seen in the closely related Drosophila simulans. We backcrossed Y chromosomes from three geographic locations into five genetic backgrounds and found strong Y and genetic background effects on male fertility. There was a significant Y‐background interaction, indicating substantial epistasis between the Y and autosomal genes affecting male fertility. This supports accumulating evidence that interactions between the Y chromosome and the autosomes are key determinants of male fitness.     

Cytological identification of two X-chromosome types in the wood lemming (Myopus schisticolor)

In the wood lemming (Myopus schisticolor) three genetic types of sex chromosome constitution in females are postulated: XX, X^*X and X^*Y (X^*=X with a mutation inactivating the male determining effect of the Y chromosome). Males are all XY. It is shown in the present paper that the two types of X chromosomes, X and X^*, exhibit differences in the G-band patterns of their short arms. In addition, it was demonstrated in unbanded chromosomes that the short arm in X^* is shorter than in X. The origin of these differences is still obscure; but they allow to identify and to distinguish the individual types of sex chromosome constitution, as of XX versus X^*X females and of X^*Y females versus XY males, on the basis of G-banded chromosome preparations from somatic cells.     

Within‐population Y‐linked genetic variation for lifespan in Drosophila melanogaster

The view that the Y chromosome is of little importance for phenotypic evolution stems from early studies of Drosophila melanogaster. This species’ Y chromosome contains only 13 protein‐coding genes, is almost entirely heterochromatic and is not necessary for male viability. Population genetic theory further suggests that non‐neutral variation can only be maintained at the Y chromosome under special circumstances. Yet, recent studies suggest that the D. melanogaster Y chromosome trans‐regulates hundreds to thousands of X and autosomal genes. This finding suggests that the Y chromosome may play a far more active role in adaptive evolution than has previously been assumed. To evaluate the potential for the Y chromosome to contribute to phenotypic evolution from standing genetic variation, we test for Y‐linked variation in lifespan within a population of D. melanogaster. Assessing variation for lifespan provides a powerful test because lifespan (i) shows sexual dimorphism, which the Y is primarily predicted to contribute to, (ii) is influenced by many genes, which provides the Y with many potential regulatory targets and (iii) is sensitive to heterochromatin remodelling, a mechanism through which the Y chromosome is believed to regulate gene expression. Our results show a small but significant effect of the Y chromosome and thus suggest that the Y chromosome has the potential to respond to selection from standing genetic variation. Despite its small effect size, Y‐linked variation may still be important, in particular when evolution of sexual dimorphism is genetically constrained elsewhere in the genome.     

Chromosome painting of Y chromosomes and isolation of a Y chromosome-specific repetitive sequence in the dioecious plant Rumex acetosa

The dioecious plant Rumex acetosa has a multiple sex chromosome system: XX in female and XY₁Y₂ in male. Both types of Y chromosome were isolated from chromosome spreads of males by manual microdissection, and their chromosomal DNA was amplified using degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR). When the biotin-labeled DOP-PCR product was hybridized with competitor DNA in situ, the fluorescent signal painted the Y chromosomes. A library of Y chromosome DNA was constructed from the DOP-PCR product and screened for DNA sequences specific to the Y chromosome. One Y chromosome-specific DNA sequence was identified and designated RAYSI (R. acetosa Y chromosome-specific sequence I). RAYSI is a tandemly arranged repetitive DNA sequence that maps to the 4’,6-diamidino-2-phenylindole bands of both Y chromosomes. Received: 22 December 1998; in revised form: 22 March 1999 / Accepted: 23 March 1999     

When gender matters: new insights into the relationships between social systems and the genetic structure of human populations

Due to its important effects on the ecological dynamics and the genetic structure of species, biologists have long been interested in gender‐biased dispersal, a condition where one gender is more prone to move from the natal site. More recently, this topic has attracted a great attention from human evolutionary geneticists. Considering the close relations between residential rules and social structure, gender‐biased dispersal is, in fact, regarded as an important case study concerning the effects of socio‐cultural factors on human genetic variation. It all started with the seminal paper by Mark Seielstad, Erich Minch and Luigi Luca Cavalli Sforza from Stanford University (Seielstad et al. 1998). They observed a larger differentiation for Y‐chromosome than mitochondrial DNA between extant human populations, purportedly a consequence of the prevalence of long‐term patrilocality in human societies. Subsequent studies, however, have highlighted the need to consider geographically close and culturally homogeneous groups, disentangle signals due to different peopling events and obtain unbiased estimates of genetic diversity. In this issue of Molecular Ecology, not only do Marks et al. (2012) adopt an experimental design which addresses these concerns, but they also take a further and important step forward by integrating the genetic analysis of two distant populations, the Basotho and Spanish, with data regarding migration rates and matrimonial distances. Using both empirical evidence and simulations, the authors show that female‐biased migration due to patrilocality might shape the genetic structure of human populations only at short ranges and under substantial differences in migration rates between genders. Providing a quantitative framework for future studies of the effects of residential rules on the human genome, this study paves the way for further developments in the field. On a wider perspective, Marks et al.'s work demonstrates the power of approaches which integrate biological, cultural and demographic lines of evidence in the study of relations between social and genetic structures of human populations.     

Distribution of heterochromatin on the mitotic chromosomes of Musca domestica L. in relation to the activity of male-determining factors

In the housefly, male sex is determined by a dominant factor, M, located either on the Y, on the X, or on any of the five autosomes. M factors on autosome I and on fragments of the Y chromosome show incomplete expressivity, whereas M factors on the other autosomes are fully expressive. To test whether these differences might be caused by heterochromatin-dependent position effects, we studied the distribution of heterochromatin on the mitotic chromosomes by C-banding and by fluorescence in situ hybridization of DNA fragments amplified from microdissected mitotic chromosomes. Our results show a correlation between the chromosomal position of M and the strength of its male-determining activity: weakly masculinizing M factors are exclusively located on chromosomes with extensive heterochromatic regions, i.e., on autosome I and on the Y chromosome. The Y is known to contain at least two copies of the M factor, which ensures a strong masculinizing effect despite the heterochromatic environment. The heterochromatic regions of the sex chromosomes consist of repetitive sequences that are unique to the X and the Y, whereas their euchromatic parts contain sequences that are ubiquitously found in the euchromatin of all chromosomes of the complement. Received: 20 February 1998; in revised form: 11 May 1998 / Accepted: 23 May 1998     

Non-recombining chromosome Y haplogroups and centromeric HindIII RFLP in relation to blood pressure in 2,743 middle-aged Caucasian men from the UK

Evidence from rodents and association analyses in humans suggest the presence on chromosome Y of one or more genes affecting blood pressure (BP). The HindIII centromeric alphoid polymorphism has been reported to be associated with BP in three independent human populations, although other studies reported null associations with this trait. Our objective was to test for association between BP and genetic variation of the Y chromosome. To this end, 2,743 unrelated Caucasian men recruited from nine UK practices were analysed for five SNPs (including the HindIII site) and two microsatellites spanning the non-recombining region of the Y chromosome. Systolic and diastolic BP were analysed both as quantitative traits and as categorical variables. Differences between locations were tested. Haplotypic and linkage disequilibrium (LD) analyses were also performed. Overall, no significant association was found between any of the loci analysed and BP, although post hoc analyses suggest a possible relation of specific Y haplogroups to BP. The HindIII polymorphism marks major structural differences in the Y centromere which could infuence mitotic loss during ageing, or other somatic events. However, this study does not support a causal effect on BP, although association of one or more Y haplogroups cannot be excluded.Electronic Supplementary Material Supplementary material is available for this article at     

Genetic factors affecting normal growth of testes inDrosophila hydei

Summary A marked growth in the length of testes ofDrosophila hydei males occurred during pupal development. This growth continued over the first 8 days of adult life and in the young adults sperm were not produced until the testes increased approximately threefold in length to about 28 mm. The length of testes is correlated with genetic factors on the X and Y chromosomes. In males lacking a Y chromosome (X/O) or the short arm (Y^S) of the Y chromosome (X/Y^L) the testes were about half the length of testes of control males (X/Y) or double Y males (X/Y/Y). Males with deletions of the distal Y^L chromosome arm had testicular lengths equivalent to the controls. Males with short testes (X/O and X/Y^L) showed disruptions to spermatogenesis at meiosis and an absence of normal spermatid elongation. Reduction of active ribosomal RNA genes on the X chromosome in X/O caused an increased expression ofbobbed (bb) and a corresponding reduction in length of testes. Severelybobbed X/O males had very few cysts of spermatogonia and these cysts did not develop into primary spermatocytes.     

Independence between modification of genetic position effects and formation of lampbrush loops by the Y chromosome of Drosophila hydei

Summary The phenotype of the variegation position effect white-mottled-2 in Drosophila hydei is modified by supernumerary Y chromosomes and by fractions thereof. Different translocated Y fragments have varying degrees of effectiveness in suppressing the mutant phenotype in the mottled eyes. In fragments derived from similar regions of the Y chromosome the suppressive ability is related to their cytological lengths. In contrast, fragments derived from distinctive regions of the Y chromosome differ markedly in their effectiveness, and these differences are not necessarily correlated with the cytological length. In particular, fragments of the distal region of Y^L are more effective in enhancing the wild phenotype than are proximal fragments of similar size.The mutation white-mottled-2 is accompanied by a complex rearrangement of the X chromosome. This inhibits crossing over between large regions of the X chromosome in structural heterozygotes; it causes also a delay of development and a considerable reduction of viability in homozygous females and hemizygous males. XO males are inviable. The inviability of these males is partially covered by Y fragments. With respect to viability, the fragments show similar regional differences in effectiveness as in the modification of the mottled phenotype.There is also a parental effect on the modulation of the white-mottled-2 phenotype.There is no correlation between the activity of Y chromosomal factors on spermiogenesis and the activity of Y factors on the modification of the variegation position effect. Suppression of Y chromosomal sites which normally unfold lampbrush loops during the spermatocyte stage and whose activity has previously been shown to be indispensible for normal differentiation of the male germ line cells does not result in any visible alterations of the effectiveness on the mottling. So there is obviously independence between these two different genetic activities of Y chromosomal factors.     

Common Mechanisms of Y Chromosome Evolution

Y chromosome evolution is characterized by the expansion of genetic inertness along the Y chromosome and changes in the chromosome structure, especially the tendency of becoming heterochromatic. It is generally assumed that the sex chromosome pair has developed from a pair of homologues. In an evolutionary process the proto-Y-chromosome, with a very short differential segment, develops in its final stage into a completely heterochromatic and to a great extends genetically eroded Y chromosome. The constraints evolving the Y chromosome have been the objects of speculation since the discovery of sex chromosomes. Several models have been suggested. We use the exceptional situation of the in Drosophila mirandato analyze the molecular process in progress involved in Y chromosome evolution. We suggest that the first steps in the switch from a euchromatic proto-Y-chromosome into a completely heterochromatic Y chromosome are driven by the accumulation of transposable elements, especially retrotransposons inserted along the evolving nonrecombining part of the Y chromosome. In this evolutionary process trapping and accumulation of retrotransposons on the proto-Y-chromosome should lead to conformational changes that are responsible for successive silencing of euchromatic genes, both intact or already mutated ones and eventually transform functionally euchromatic domains into genetically inert heterochromatin. Accumulation of further mutations, deletions, and duplications followed by the evolution and expansion of tandem repetitive sequence motifs of high copy number (satellite sequences) together with a few vital genes for male fertility will then represent the final state of the degenerated Y chromosome. This revised version was published online in July 2006 with corrections to the Cover Date.     

Selection of DNA sequences from interval 6 of the human Y chromosome with homology to a Y chromosomal fertility gene sequence of Drosophila hydei

Summary An experimental approach towards the molecular analysis of the male fertility function, located in interval 6 of the human Y chromosome, is presented. This approach is not based on the knowledge of any gene product but on the assumption that the functional DNA structure of male fertility genes, evolutionary conserved with their position on the Y chromosome, may contain an evolutionary conserved frame structure or at least conserved sequence elements. We tested this hypothesis by using dhMiF1, a fertility gene sequence of the Y chromosome of Drosophila hydei, as a screening probe on a pool of cloned human Y-DNA sequences. We were able to select 10 human Y-DNA sequences of which 7 could be mapped to Y interval 6 (the pY6H sequence family). Since the only fertility gene of the human Y chromosome is mapped to the same Y interval, our working hypothesis seems to be strongly supported. Most interesting in this respect is the isolation of the Y-specific repetitive pY6H65 sequence. The pY6H65 locus extends to a length of at least 300 kb in Y interval 6 and has a locus-specific repetitive sequence organization, reminiscent of the functional DNA structure of Y chromosomal fertility genes of Drosophila. We identified the simple sequence family (CA)_n as one sequence element conserved between the Drosophila dhMiFi fertility gene sequence and the homologous human Y-DNA sequences.     

Neuropeptide Y Receptor Genes on Human Chromosome 4q31–q32 Map to Conserved Linkage Groups on Mouse Chromosomes 3 and 8

Npy1randNpy2r,the genes encoding mouse type 1 and type 2 neuropeptide Y receptors, have been mapped by interspecific backcross analysis. Previous studies have localized the human genes encoding these receptors to chromosome 4q31–q32. We have now assignedNpy1randNpy2rto conserved linkage groups on mouse Chr 8 and Chr 3, respectively, which correspond to the distal region of human chromosome 4q. Using yeast artificial chromosomes, we have estimated the distance between the human genes to be approximately 6 cM. Although ancient tandem duplication events may account for some closely spaced G-protein-coupled receptor genes, the large genetic distance between the human type 1 and type 2 neuropeptide Y receptor genes raises questions about whether this mechanism accounts for their proximity.     

Conservation of human Y chromosome sequences among male great apes: Implications for the evolution of Y chromosomes

Nine newly described single-copy and lowcopy-number genomic DNA sequences isolated from a flow-sorted human Y chromosome library were mapped to regions of the human Y chromosome and were hybridized to Southern blots of male and female great ape genomic DNAs (Gorilla gorilla, Pan troglodytes, Pongo pygmaeus). Eight of the nine sequences mapped to the euchromatic Y long arm (Yq) in humans, and the ninth mapped to the short arm or pericentromeric region. All nine of the newly identified sequences and two additional human Yq sequences hybridized to restriction fragments in male but not female genomic DNA from the great apes, indicating Y chromosome localization. Seven of these 11 human Yq sequences hybridized to similarly-sized restriction endonuclease fragments in all the great ape species analyzed. The five human sequences that mapped to the most distal subregion of Yq (deletion of which region is associated with spermatogenic failure in humans) were hybridized to Southern blots generated by pulsed-field gel electrophoresis. These sequences define a region of approximately 1 Mb on human Yq in which HpaII tiny fragment (HTF) islands appear to be absent. The conservation of these human Yq sequences on great ape Y chromosomes indicates a greater stability in this region of the Y than has been previously described for most anonymous human Y chromosomal sequences. The stability of these sequences on great ape Y chromosomes seems remarkable given that this region of the Y does not undergo meiotic recombination and the sequences do not appear to encode genes for which positive selection might occur. Correspondence to: B. Steele Allen     

3H-Actinomycin-D binding to mitotic chromosomes of Drosophila melanogaster

The binding of ³H-AMD to the metaphase chromosomes of Drosophila melanogaster has been analyzed after two different periods of exposure to photographic emulsion. The entirely heterochromatic Y chromosome was markedly less labelled than euchromatin and other heterochromatic regions. Moreover, the few grains present on the Y chromosome were clustered in two regions, one localized in the middle of Y^S and the other in the proximal third of Y^L. This labelling pattern is not affected by removing histones with a 2-hour treatment with 2N HCl. It is suggested that the specific underlabelling of the Y chromosome reflects a peculiar AT richness.     

A marked ring-Y-chromosome in Drosophila hydei with a new type of white variegation

A ring-Y chromosome, R(Y)w ^m, of D. hydei is described which carries a complete set of fertility genes, a NOR region and a small X-chromosomal insertion (w ^m), which may be used as a marker. The ring has been characterized by various staining techniques. It was derived from a w ^mCo Y chromosome by X-ray treatment of spermatocytes. Its mode of origin allows to fix the gene order in the distal region of the long arm of the w ^mCoY chromosome. The white ⁺ gene included in the ring shows a new type of position-effect variegation which is described and discussed in the context of an earlier hypothesis on a dual function of the white locus.