Dispersion of argininosuccinate synthetase-like human genes to multiple autosomes and the X chromosome

DNA sequences closely homologous to argininosuccinate synthetase are present at ten or more distinct locations in the human genome, including sites on chromosomes 6,9 and X. Argininosuccinate synthetase thus represents one of the most widely dispersed multigene families described to date, the first instance of a multigene family associated with an enzyme of intermediary metabolism and, perhaps most striking, the first instance of a multigene family with members on both autosomes and sex chromosomes.     

Isolation and characterization of cloned human DNA fragments carrying reiterated sequences common to both autosomes and the X chromosome.

Several recombinants were identified and purified from a cloned library of human DNA by virtue of their homology to DNA from a mouse-human hybrid cell line containing a single human chromosome, the X, and their lack of homology to mouse DNA. Three recombinants were characterized in detail, and all were homologous to reiterated DNA from the human X chromosome. These recombinants also were homologous to reiterated sequences on one or more human autosomes and, therefore, were not X chromosome specific. The recombinant DNA fragments homologous to human reiterated X DNA were the same fragments homologous to human reiterated autosomal DNA. Digestion of genomic DNAs with several restriction enzymes revealed that the pattern of fragments homologous to one recombinant, lambda Hb2, was the same on autosomes as on the X chromosome, suggesting that the molecular organization of these elements on the X is not distinct from their organization on autosomes.     

Scale-specific sex-biased dispersal in the Valais shrew unveiled by genetic variation on the Y chromosome, autosomes, and mitochondrial DNA

We investigated sex specificities in the evolutionary processes shaping Y chromosome, autosomes, and mitochondrial DNA patterns of genetic structure in the Valais shrew (Sorex antinorii), a mountain dwelling species with a hierarchical distribution. Both hierarchical analyses of variance and isolation-by-distance analyses revealed patterns of population structure that were not consistent across maternal, paternal, and biparentally inherited markers. Differentiation on a Y microsatellite was lower than expected from the comparison with autosomal microsatellites and mtDNA, and it was mostly due to genetic variance among populations within valleys, whereas the opposite was observed on other markers. In addition, there was no pattern of isolation by distance for the Y, whereas there was strong isolation by distance on mtDNA and autosomes. We use a hierarchical island model of coancestry dynamics to discuss the relative roles of the microevolutionary forces that may induce such patterns. We conclude that sex-biased dispersal is the most important driver of the observed genetic structure, but with an intriguing twist: it seems that dispersal is strongly male biased at large spatial scale, whereas it is mildly biased in favor of females at local scale. These results add to recent reports of scale-specific sex-biased dispersal patterns, and emphasize the usefulness of the Y chromosome in conjunction with mtDNA and autosomes to infer sex specificities.     

On the localization of genes on certain autosomes of man through chromosome aberrations

Summary Chromosome aberrations permit the assignment to and the exclusion of genes on certain chromosomes or definite segments. Only exclusion methods are discussed. All relevant data are compiled in a table from which it can be determined, which genetic systems are excluded from certain autosomal segments.

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Zusammenfassung Angeborene Chromosomenaberrationen ermöglichen die Zuordnung und den Ausschluß von Genen auf dem betroffenen Segment. Nur die für Lokalisierungsausschlüsse verwendbaren Methoden werden diskutiert. Aus einer Zusammenstellung der bisherigen Befunde wird ermittelt, welche genetischen Systeme von einer Lokalisierung auf bestimmten Autosomen(segmenten) des Menschen ausgeschlossen werden können.

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Direktor: Prof. Dr. Dr. H. Baitsch

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Supported by the Deutsche Forschungsgemeinschaft.     

The evolution of sex-biased genes and sex-biased gene expression

Differences between males and females in the optimal phenotype that is favoured by selection can be resolved by the evolution of differential gene expression in the two sexes. Microarray experiments have shown that such sex-biased gene expression is widespread across organisms and genomes. Sex-biased genes show unusually rapid sequence evolution, are often labile in their pattern of expression, and are non-randomly distributed in the genome. Here we discuss the characteristics and expression of sex-biased genes, and the selective forces that shape this previously unappreciated source of phenotypic diversity. Sex-biased gene expression has implications beyond just evolutionary biology, including for medical genetics.     

Sebida: a database for the functional and evolutionary analysis of genes with sex-biased expression

We describe Sebida, a database of genes with sex-biased expression. The database integrates results from multiple, independent microarray studies comparing male and female gene expression in Drosophila melanogaster, Drosophila simulans and Anopheles gambiae. Sebida uses standard nomenclature, which allows individual genes to be compared across different microarray platforms and to be queried by gene name, symbol, or annotation number. In addition to ratios of male/female expression for each gene, Sebida also contains information useful for evolutionary studies, such as local recombination rate, degree of codon bias and interspecific divergence at synonymous and non-synonymous sites. AVAILABILITY: Sebida can be accessed at http://www.sebida.de     

Looking for signatures of sex-specific demography and local adaptation on the X chromosome

A population study comparing X-linked variation with that of the autosomes reveals that social organization has a clear impact on X chromosome genetic diversity and that the X chromosome shows a signature of local adaptation.     

The X chromosome shows less genetic variation at restriction sites than the autosomes.

Using a standard technique, 122 single-copy probes were screened for their ability to detect restriction fragment length polymorphisms (RFLPs) in the human genome. The use of a standardized RFLP screening enables the introduction of statistical methods in the analysis of differences in RFLP content between chromosomes and enzymes. RFLPs were detected from panels containing at least 17 unrelated chromosomes, digested with TaqI, MspI, BglII, HindIII, EcoRI, and PstI. Forty autosomal probes, representing a sample of 2,710 base pairs (bp) per haploid genome, were tested, and 24 RFLPs were found. With 82 X-chromosomal probes, 17 RFLPs were found in 6,228 bp per haploid genome. The frequency of X-chromosomal RFLPs is three times less than that of the autosomes; this difference is highly significant (P = less than .001). The frequency of RFLPs revealed by various restriction enzymes and the possibility that the X chromosome is a "low mutation" niche in the human genome are discussed.     

Methylation profile of genes on the human X chromosome

X chromosome inactivation occurs in female mammals for the purpose of equalisation of dosage of X linked genes between the two sexes. In eutherian mammals, one of the two copies of the X chromosome present in female individuals is silenced. Epigenetic modifications of both DNA and histones have been implicated to play a crucial role in this inactivation phenomenon. In this work, we have employed a novel method published earlier by us, to assess the DNA methylation levels of genes on the inactive X chromosome in the human system. We have used genomic DNA from cells with the following karyotype namely, 47,XXX and 45,X to compare methylation levels from the active and inactive X. We report differential methylation of genes from the active and the inactive X chromosome with higher number of methylated genes being present on the inactive X chromosome. Our work has also led to identification of motifs that show a significant similarity to microRNA sequences which are enriched in methylated regions specific to the inactive X.     

Evolutionary relationships of the Chinese hamster X chromosome and autosomes: a comparison using solution hybridization techniques

The evolutionary relationships of Chinese hamster X chromosome and autosome DNA sequences were compared by solution hybridization techniques. Chinese hamster X chromosome tracer was prepared by radiolabeling DNA from chromosomes isolated by fluorescence-activated sorting. Radiolabeled Chinese hamster total genomic DNA, approximately 90% of which is of autosome origin, was used as autosome tracer. Each tracer was mixed with excess driver DNA of Chinese hamster, Syrian hamster, rat, rabbit, cat, cow, or human origin. Reaction mixtures were melted and allowed to reassociate to an equivalent CoT of 12000, under conditions which permitted 35% mismatch in DNA duplexes. Both the extent of duplex formation (the normalized percentage hybridization or NPH) and the average thermal stability of the duplexes formed (melting temperature or Tm) were measured; these values were used to compare the evolutionary relatedness of tracer and driver DNAs. The pattern of evolutionary relatedness revealed by comparing either the Tm or NPH values obtained with different drivers was the same for X chromosome and autosome DNA and was consistent with the phylogeny of the species examined. Although NPH and Tm values for X chromosome and autosome tracers differed, differences fell within the range of experimental error. The results of these studies provide no evidence for differential conservation of Chinese hamster X chromosome sequences, suggesting that the constraints on the mammalian X chromosome which act to maintain its gene linkage group intact do not markedly reduce the extent to which its sequences diverge during evolution.     

X for intersection: retrotransposition both on and off the X chromosome is more frequent

As the heteromorphic sex chromosomes evolved from a pair of autosomes, the sex chromosomes became increasingly different in gene content and structure from each other and from the autosomes. Although recently there has been progress in documenting and understanding these differences, the molecular mechanisms that have fashioned some of these changes remain unclear. A new study addresses the differential distribution of retroposed genes in human and mouse genomes. Surprisingly, chromosome X is a major source and a preferred target for retrotransposition.     

Quantifying the relative contributions of the X chromosome,autosomes, and mitochondrial genome to local adaptation*

During local adaptation with gene flow, some regions of the genome are inherently more responsive to selection than others. Recent theory predicts that X‐linked genes should disproportionately contribute to local adaptation relative to other genomic regions, yet this prediction remains to be tested. We carried out a multigeneration crossing scheme, using two cline‐end populations of Drosophila melanogaster, to estimate the relative contributions of the X chromosome, autosomes, and mitochondrial genome to divergence in four traits involved in local adaptation (wing size, resistance to heat, desiccation, and starvation stresses). We found that the mitochondrial genome and autosomes contributed significantly to clinal divergence in three of the four traits. In contrast, the X made no significant contribution to divergence in these traits. Given the small size of the mitochondrial genome, our results indicate that it plays a surprisingly large role in clinal adaptation. In contrast, the X, which represents roughly 20% of the Drosophila genome, contributes negligibly—a pattern that conflicts with theoretical predictions. These patterns reinforce recent work implying a central role of mitochondria in climatic adaptation, and suggest that different genomic regions may play fundamentally different roles in processes of divergence with gene flow.     

利用高密度SNP检测不同猪品种间X染色体选择信号

在家猪的培育过程中,许多重要的经济性状受到过高强度的人工选择,高密度SNP标记为通过选择信号检测追踪这些性状经历的选择提供了可能,并能根据选择信号利用生物信息学寻找到与选择相关的基因。X染色体由于其特殊性,在传统的遗传分析中许多针对常染色体的方法往往不适用,需要采取特殊的方法,选择信号检测可以作为一种行之有效的方法对X染色体进行分析。文章利用长白、松辽黑猪和大白3个猪品种,通过品种间选择信号检测方法 XP-EHH,利用高密度SNP标记对X染色体进行选择信号检测,并通过生物信息学分析寻找选择信号区域内重要基因。在长白、松辽黑猪和大白3个品种中分别检测出29、13和15个选择信号区域,每个选择信号区域平均包含3.59、4.92、4.07个SNPs,长白和松辽黑猪、长白和大白有部分重叠选择信号区域,大白和松辽黑猪没有发现重叠选择信号区域。生物信息学分析发现各品种选择信号区域内有与繁殖、免疫等性状相关基因,其中部分在猪中尚未见报道,可作为研究猪相关性状的重要候选基因。     

Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes.     

Regulatory links between imprinted genes: evolutionary predictions and consequences

Genomic imprinting is essential for development and growth and plays diverse roles in physiology and behaviour. Imprinted genes have traditionally been studied in isolation or in clusters with respect to cis-acting modes of gene regulation, both from a mechanistic and evolutionary point of view. Recent studies in mammals, however, reveal that imprinted genes are often co-regulated and are part of a gene network involved in the control of cellular proliferation and differentiation. Moreover, a subset of imprinted genes acts in trans on the expression of other imprinted genes. Numerous studies have modulated levels of imprinted gene expression to explore phenotypic and gene regulatory consequences. Increasingly, the applied genome-wide approaches highlight how perturbation of one imprinted gene may affect other maternally or paternally expressed genes. Here, we discuss these novel findings and consider evolutionary theories that offer a rationale for such intricate interactions among imprinted genes. An evolutionary view of these trans-regulatory effects provides a novel interpretation of the logic of gene networks within species and has implications for the origin of reproductive isolation between species.     

Contrasting the efficacy of selection on the X and autosomes in Drosophila

To investigate the relative efficacy of both positive and purifying natural selection on the X chromosome and the autosomes in Drosophila, we compared rates and patterns of molecular evolution between these chromosome sets using the newly available alignments of orthologous genes from 12 species. Parameters that may influence the relative X versus autosomal substitution rates include the relative effective population sizes, the male and female germline mutation rates, the distribution of allelic effects on fitness, and the degree of dominance of novel mutations. Our analysis reveals that codon usage bias is consistently greater for X-linked genes, suggesting that purifying selection consistently has greater efficacy on the X chromosome than on the autosomes across the Drosophila phylogeny. However, our results are less consistent with respect to the efficacy of positive selection, with only some lineages showing a higher substitution rate on the X chromosome. This suggests that either the distribution of selective effects of mutations or other relevant parameters are sufficiently variable across species to tip the balance in different ways in individual lineages. These data suggest that rates of substitution are not solely governed by adaptive evolution. This genome-wide analysis provides a clear picture that the efficacy of selection varies intragenomically and that this effect is markedly more consistent across the phylogeny in the case of purifying selection. Our results also suggest that simple models that predict systematic differences in rates of evolution between the X and the autosomes can only be made to be compatible with these Drosophila data if the relevant population genetic parameters that drive substitution rates differ among species and chromosomal contexts.