The most common source of new genes in eukaryotic lineages is gene duplication, which creates copy number variation of an existing gene in the genome. The resulting genes (paralogs) may then diverge in sequence and in function. Sets of genes formed in this way compose a gene family. Gene duplications and losses within a family are common and represent a major source of evolutionary biodiversity. Sometimes, gene duplication may result in a nonfunctional copy of a gene, or a functional copy may be subject to mutations that result in loss of function; such nonfunctional genes are called pseudogenes.
"Orphan" genes, whose sequence shows no similarity to existing genes, are less common than gene duplicates. The human genome contains an estimate 18 to 60 genes with no identifiable homologs outside humans. Orphan genes arise primarily from either de novo emergence from previously non-coding sequence, or gene duplication followed by such rapid sequence change that the original relationship becomes undetectable. De novo genes are typically shorter and simpler in structure than most eukaryotic genes, with few if any introns. Over long evolutionary time periods, de novo gene birth may be responsible for a significant fraction of taxonomically restricted gene families.
Horizontal gene transfer refers to the transfer of genetic material through a mechanism other than reproduction. This mechanism is a common source of new genes in prokaryotes, sometimes thought to contribute more to genetic variation than gene duplication. It is a common means of spreading antibiotic resistance, virulence, and adaptive metabolic functions. Although horizontal gene transfer is rare in eukaryotes, likely examples have been identified of protist and alga genomes containing genes of bacterial origin.