The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome1. 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 ∼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 selection2 - these include the major defensin (DEF) gene cluster3,4 and MCPH15,6, 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.
Bibliographical noteFunding Information:
Acknowledgements We thank L. Gaffney for help with figures and tables; L. French and her group at the Sanger Institute for attempting fibre FISH analysis to size some clone gaps in the tiling path of chromosome 8; E. Eichler and X. She for sharing their data on segmental duplications; T. Furey for help with lists of genetic markers and placement of RefSeq genes; M. Kamal for assistance and advice with synteny analysis; and K. Lindblad-Toh for sharing data from the dog genome project. We also acknowledge the HUGO Gene Nomenclature Committee (S. Povey, chair) for assigning official gene symbols. We are deeply grateful to all the members, present and past, of the Genome Sequencing Platform of the Broad Institute (and Whitehead Center for Genome Research), Keio University School of Medicine and the Institute of Molecular Biology at Jena for their dedication and for the consistent high quality of their data that made this work possible. This work was supported by grants from the National Human Genome Research Institute, RIKEN, the ‘Research for the Future’ Program from the Japan Society for the Promotion of Science (JSPS), the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), the Federal German Ministry of Education, Research and Technology, and the Thüringer Kultusministerium.