Cytokines & Cells Online Pathfinder Encyclopaedia
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A term used to describe genes that display enough nucleotide sequence homologies to permit their classification as a member of a group of related genes. Such genes have usually arisen from a common ancestor by gene duplication or amplification and have diverged subsequently by mutations. Examples of such families of genes are the genes encoding ribosomal RNA, some histone and globin genes (alpha-globins and beta-globins), genes encoding human Growth hormone, actin genes, genes encoding serine proteases, vitellogenin genes, and major histocompatibility antigen genes.
It has been proposed that the term family be used for proteins that have very closely related sequences with greater than 50 % amino acid identity.
A Gene superfamily or multigene family consists of groups of genes that do not show a marked homology among each other. Nevertheless, they are related to each other by the occurrence of subdomains within the proteins encoded by them. These subdomains or sequence motifs are identified as highly similar regions in alignments of protein segments and are the smallest sequence units of protein families (see also the Protein domains Dictionary section of this encyclopedia). The genes belonging to a gene superfamily encode proteins that are, accordingly, classified as belonging to a particular protein family. Examples are genes encoding immunoglobulins, genes encoding serine proteases, many enzymes and receptors, and many genes encoding cytokine receptors (see: Cytokine receptor families) or cytokines.
The term superfamily is used for proteins showing less than 50 % sequence identity but related in evolution and to have similar structures and types of function.
If sequences and sequence characteristics have been preserved evolutionarily this may suggest also similar protein folding patterns and functional properties.
When talking about gene families one often encounters the terms homolog, ortholog, or paralog.
A homolog is a gene that descended from a common gene ancestor. There are, of course, modifications introduced, for example, by mutation events. Shared ancestry is not necessarily the same as similarity! Most homologous genes are similar but many similar genes are not homologous.
An ortholog actually is a homolog generated by speciation events. The functions of such genes have been conserved and are basically the same in different species. The common evolutionary history of such genes does not, for example, reveal the existence of gene duplication events as an underlying prerequisite for divergence.
A paralog is also a homolog within the same species. These genes have been generated by gene duplication events and divergence and have evolved different functions in the same species. Numerous genes have been conserved in this way through evolutionary history. The protein products of these genes, therefore, can be identified frequently in species comprising mammalian cells, yeast, fruit fly, or nematodes (for example Caenorhabditis elegans). One example showing the relationships between these different genes is homeobox genes discovered originally in Drosophila melanogaster. The original homeobox gene (Hox gene) in invertebrates duplicated and evolved into several paralogs. During the transition to vertebrates, the entire Hox gene cluster duplicated into four copies that then diverged. During this process some of the paralogs got lost and others evolved novel functions in development. Alpha-globin, beta-globin, and myoglobin are classical examples of paralogs that arose from duplications of ancestral globin genes in the vertebrate lineage
Some designations used in research on cytokines such as Interleukins or Lymphokines, or colony stimulating factors, for example, have no structural similarities as their common name might imply.
Large superfamilies of cytokines include the TGF-beta superfamily (comprising various TGF-beta isoforms, Activin A, Inhibins, BMP (Bone morphogenetic proteins), dpp (decapentaplegic) and some others), the PDGF superfamily (including VEGF), the EGF superfamily (including EGF, TGF-alpha, AR (amphiregulin), Betacellulin, HB-EGF, and some others), The VEGF family, Chemokines (with various subfamilies defined by their structures), FGF (Fibroblast growth factors), the family of neurotrophins.
For techniques allowing identification of gene families see: gene library.
LAST MODIFIED: January 2002
See REFERENCES for entry Gene family
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