5 minute read

Gene Families

Gene families are groups of DNA segments that have evolved by common descent through duplication and divergence. They are multiple DNA segments that have evolved from one common ancestral DNA segment that has been copied and changed over millions of years.

The members of a gene family may include expressed genes as well as nonexpressed sequences. Such nonexpressed sequences include promoters, operators, transposable genetic elements, and pseudogenes, which are genes that are no longer functionally expressed.

Pseudogenes resemble other family members in their linear sequence of nucleotides. However, they usually either lack the signals that would allow them to be expressed or have significant deletions or rearrangements that prevent successful transcription or translation.

One well-studied gene family is that of the globins, shown in both Figures 1 and 2. The globin family contains many pseudogenes as well as many functional genes, including the genes coding for hemoglobins (α, β, γ, δ).

Gene families vary enormously in size and number, ranging, in the human genome, from just a few copies of very closely related sequences to more than a half-million copies of Alu sequences, which are transposable Figure 1. Evolution of the globin genes. The numbers in parentheses represent the estimated number of nucleotide changes needed to account for the observed amino acid differences. Adapted from <http://www.cord.edu/faculty/landa/courses/b315f99/sessions/phylogeny/globinPhylogeny.jpg>. genetic elements with no known function. For genes that encode proteins, duplicate copies of genes have been found for over 2,000 proteins in a variety of genomes.

Members of gene families may be located in contiguous clusters on one chromosome, or they may be scattered throughout a genome. Homeotic genes, which lie in contiguous clusters on a few chromosomes, provide the best example of evolutionarily preserved gene order within a gene family. These genes play a role in the spatial development of the anterior-posterior axis of vertebrates and invertebrates. Four binary axes are laid down early in the basal body plan of most metazoans, including us: anterior-posterior, dorsal-ventral, left-right, and inside-outside. They affect locations on the body axis in roughly the same order as they are arranged along a chromosome, even though different clusters appear on different chromosomes. Amazingly, these genes work about the same in a fruit fly as they do in a human in establishing linear arrangements.

In some gene families, related genes have stayed together over long periods of evolution, while in other gene families, members have become widely distributed within genomes. In ribosomal RNA genes, tandem arrays, in which multiple copies of the same gene occur one after another, have been observed. On the other hand, in the globin gene family, both the order and distribution of the genes, which are not identical, vary widely, even within one taxonomic group such as the mammals.

Members of a gene family usually have similar structures, but they may have diverged evolutionarily to such an extent that they are expressed in different ways. They may be expressed at different times in the development of multicellular organs or in different cells and tissues, and they may have acquired different functions. They may even have been transferred between organisms that are not closely related by evolution.

Figure 2. Representations of the two clusters of genes that code for human globin, the protein portion of hemoglobin. Adapted from <http://www.irn.pdx.edu/~newmanl/GlobinGeneEvolution.GIF>.

One controversy about gene families involves whether they have arisen primarily by polyploidy or via tandem gene duplications. Polyploidy means that full genomes in an organism are duplicated either by mitosis or meiosis without cytokinesis or by matings between organisms with unequal numbers of chromosomes. This is followed by full copying of both parents' full genomes so each haploid set of chromosomes is now diploid. In tandem duplication, one or more copies of a gene lie on the same chromosome adjacent to one another. Polyploidy has been invoked to explain the evolution of complex new functions in taxa. Researchers give five reasons. Polyploids:

  1. have "higher levels of heterozygosity than do their diploid parents";
  2. "exhibit less inbreeding depression than do their diploid parents";
  3. "are polyphyletic … [which] … incorporates genetic diversity from multiple progenitor populations" and, thus, they have higher genetic diversity "than expected by models of polyploid formation involving a single origin";
  4. have genome rearrangements that are common; and
  5. are like duplicated genes, freed from intense selection pressure, which allows frequent evolution of new functions (Soltis and Soltis 2000, p. 310).

Austin Hughes has been the major critic of the often invoked polyploid hypothesis for origin of major animal groups because of the major substitutional load that would be involved and molecular phylogenetic evidence against it (1999, pp. 205-212). However, the results of most molecular evolutionary studies are more consistent with the gradualist view that new functions are generated primarily by tandem gene duplication and divergence of both sequence and function, spread over a long time.

John R. Jungck


Henikoff, Steven, et al. "Gene Families: The Taxonomy of Protein Paralogs and Chimeras." Science 278 (1997): 609-614.

Holmes, Roger S., and Hwa A. Lim, eds. Gene Families: Structure, Function, Genetics and Evolution. Singapore: World Scientific Publishers, 1996.

Hughes, Austin L. Adaptive Evolution of Genes and Genomes. New York: Oxford University Press, 1999.

Page, Roderic D. M., and Edward C. Holmes. Molecular Evolution: A Phylogenetic Approach. Malden, MA: Blackwell Science, 1998.

Patthy, Laszló. Protein Evolution. Malden, MA: Blackwell Science, 1999.

Soltis, Pamela S., and D. E. Soltis. "The Role of Genetic and Genomic Attributes in the Success of Polyploids." In Variation and Evolution in Plants and Microorganisms, Francisco J. Ayala, et al., eds. Washington, DC: National Academy Press, 2000.

Thorston, J. W., and R. DeSalle. "Gene Family Evolution and Homology: GenomicsMeets Phylogenetics." Annual Review of Genomics and Human Genetics 1 (2000): 41-73.

Internet Resources

"Phylogenic Relationships between Globin-Type Proteins." Concordia College.<http://www.cord.edu/faculty/landa/courses/b315f99/sessions/phylogeny/globinPhylogeny.jpg>.

"Proposed Evolution of Globin Genes." Portland State University. <www.irn.pdx.edu/~newmanl/GlobinGeneEvolution.GIF>.

Additional topics

Medicine EncyclopediaGenetics in Medicine - Part 2