RESUMEN
The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.
Asunto(s)
Cromosomas Humanos Par 8/genética , Evolución Molecular , Animales , Mapeo Contig , ADN Satélite/genética , Defensinas/genética , Eucromatina/genética , Femenino , Humanos , Inmunidad Innata/genética , Masculino , Datos de Secuencia Molecular , Familia de Multigenes/genética , Análisis de Secuencia de ADNRESUMEN
Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.
Asunto(s)
Cromosomas Humanos Par 17/genética , Evolución Molecular , Animales , Composición de Base , Duplicación de Gen , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Ratones , Análisis de Secuencia de ADN , Elementos de Nucleótido Esparcido Corto/genética , Sintenía/genéticaRESUMEN
Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.
Asunto(s)
Cromosomas Humanos Par 18/genética , ADN/genética , Aneuploidia , Animales , Secuencia Conservada/genética , Islas de CpG/genética , Exones/genética , Etiquetas de Secuencia Expresada , Genes/genética , Genoma Humano , Humanos , Intrones/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , SinteníaAsunto(s)
Bases de Datos Genéticas/normas , Secuenciación de Nucleótidos de Alto Rendimiento/normas , Informática Médica/normas , Técnicas de Diagnóstico Molecular/normas , Análisis de Secuencia de ADN/normas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Laboratorios/normas , Informática Médica/métodos , Técnicas de Diagnóstico Molecular/métodos , Análisis de Secuencia de ADN/métodosRESUMEN
Although often considered "minimal" organisms, mycoplasmas show a wide range of diversity with respect to host environment, phenotypic traits, and pathogenicity. Here we report the complete genomic sequence and proteogenomic map for the piscine mycoplasma Mycoplasma mobile, noted for its robust gliding motility. For the first time, proteomic data are used in the primary annotation of a new genome, providing validation of expression for many of the predicted proteins. Several novel features were discovered including a long repeating unit of DNA of approximately 2435 bp present in five complete copies that are shown to code for nearly identical yet uniquely expressed proteins. M. mobile has among the lowest DNA GC contents (24.9%) and most reduced set of tRNAs of any organism yet reported (28). Numerous instances of tandem duplication as well as lateral gene transfer are evident in the genome. The multiple available complete genome sequences for other motile and immotile mycoplasmas enabled us to use comparative genomic and phylogenetic methods to suggest several candidate genes that might be involved in motility. The results of these analyses leave open the possibility that gliding motility might have arisen independently more than once in the mycoplasma lineage.