Lineage-specific Expansion of KRAB Zinc-finger Transcription Factor Genes: Implications for the Evolution of Vertebrate Regulatory Networks

A substantial fraction of the vertebrate gene repertoireis conserved across the animal kingdom and beyond (Lander et al. 2001; Aparicio et al. 2002; Lespinet et al. 2002).In addition, unique 1:1 ortholog pairings reveal substantialdomains of syntenic conservation when closely relatedgenomes are compared (see, e.g., Dehal et al. 2001; Waterston et al. 2002). However, for certain gene types, 1:1orthologous relationships are the exception and not therule, apparently because duplicate copies of these geneshave been generated and fixed at unusually high rates.These ongoing duplication events have yielded substantialnumbers of lineage-specific genes, giving rise to generepertoire differences that distinguish even very closelyrelated species. Examples include genes encoding olfactory receptors (OR) and Krüppel-type zinc finger (KZNF)proteins, which together comprise 2–5% of known mammalian genes. Importantly, most of the genes in theserapidly expanding families exist in contiguous familialclusters, consistent with the model that they have arisenthrough a process of repeated tandem duplications (Ohno1970; Huntley et al. 2003). Although the mechanismsdriving these in situ duplications require more study, theevolutionary generation of such tandem gene arrays is responsible for the overwhelming majority of gene repertoire expansion in metazoans (Friedman and Hughes2003). What underlies this dramatic difference in evolutionary fate between these "fast-lane" genes and those inthe conserved core genome...