page_title: NUMT
section_title: Experimental uses and errors
hierarchical_section_title: NUMT / Experimental uses and errors
caption_attribution_description: English: Use of Sanger sequencing to locate NUMT insertion in the nuclear genome
context_page_description: NUMT, pronounced "new might," is an acronym for "nuclear mitochondrial DNA" segment coined by evolutionary geneticist, Jose V. Lopez, which describes a transposition of any type of cytoplasmic mitochondrial DNA into the nuclear genome of eukaryotic organisms.
  More and more NUMT sequences, with different size and length, in the diverse number of Eukaryotes, have been detected as more whole genome sequencing of different organisms accumulate. In fact, NUMTs have often been unintentionally discovered by researchers who were looking for mtDNA. NUMTs have been reported in all studied eukaryotes, and nearly all mitochondrial genome regions can be integrated into the nuclear genome. However, NUMTs differ in number and size across different species. Such differences may be accounted for by interspecific variation in such factors as germline stability and mitochondria number.
  After the release of the mtDNA to the cytoplasm, due to the mitochondrial alteration and morphological changes, mtDNA is transferred into the nucleus by one of the various predicted methods and are eventually inserted by double-stranded break repair processes into the nuclear DNA.
context_section_description: Although understanding non-random insertion of NUMT and carrying out certain function after insertion, helps with revealing the structure and determining the complete function of the genome, especially human genome, NUMTs have been used as experimental tools and have been beneficial in different biological fields even before having any knowledge about the function of NUMTs. For instance, NUMTs can be used not only as genetic markers but also as a tool for understanding the relative rate of mutation in the nucleus and the mitochondria as well as recreating evolutionary trees. The continuing process of NUMT integration into the nuclear genome is evidenced by the finding of NUMTs that have been inserted into the human genome after the human–chimpanzee divergence. Some of these NUMTs are variable with respect to the genomic presence or absence, indicating that they have only arisen recently in the human population, permitting them to be used as genetic markers of lineage. Using a protocol based on genome alignment to estimate the number of NUMT in closely related species, Hazkani-Covo and Graur could not only identify evolutionary events that may have affected NUMT composition in each genome but could also reconstruct the NUMT makeup in the common ancestor of human and chimpanzee. NUMTs can be also used to compare the rate of nonfunctional nuclear sequence evolution to that of functional mtDNA and determine the rate of evolution by the rate of mutation accumulation along NUMT sequences over time. The least selectively constrained regions are the segments with the most divergence from the mitochondrial sequence. One of the most promising applications of NUMT study is its use in the study of nuclear mutation. In metazoans, NUMTs are considered non-functional. Therefore, nuclear mutations can be distinguished from mitochondrial changes and the study of nucleotide substitution, insertion, and deletion would be possible. Additionally, the homology of paralogous NUMT sequences with the mtDNA allows testing for local sequence effects on mutation. All these information obtained from the study of NUMT fragments could be used to understand mitochondrial evolution as well as evolutionary processes throughout the history.
  NUMTs offer an opportunity to study ancient diversity of mitochondrial lineages and to discover prehistoric interspecies hybridization. Ancient hybridization have been first detected (using NUMTs) in bristletails, then in colobine monkeys, and, most recently, in a direct human ancestor. The hominid hybridization happened about the time of human/chimpanzee/gorilla separation. This latter study concerns a human NUMT shared with chimpanzee and gorilla. Joint phylogeny of the three NUMT sequences and the mitochondrial genomes of great apes implies that a common ancestor of the three NUMTs has been transferred to human/chimp/gorilla lineage from a hominid species separated from them by about 4.5 million years of mtDNA evolution. While hybridization of this magnitude is not unheard of among primates, its occurrence in the direct human lineage, around the critical time of human/ape speciation, is a startling result. Additional NUMTs with similar phylogenies indicate that such events may be not unique.
  Another problem arose from the presence of NUMT in the genome associated with the hardship of concluding the exact number of mitochondrial insertions into the nDNA. Determining the exact number of NUMT pseudogenes for a species is difficult task for several reasons. One reason that makes detection of NUMT sequences more difficult is the alteration of these sequences by mutation and deletion.  Two further substantial obstacles make recognition of NUMT very difficult; first is the lack of correlation between the proportion of noncoding nDNA and the number of NUMT inserts in the nuclear genome. That is, NUMT insertion could occur in the known or predicted coding region, both intron and exon, rather than only in intergenic and intronic region.  Second, mitochondrial DNA integrated into animal nuclear genomes is primarily limited to 
caption: Use of Sanger sequencing to locate NUMT insertion in the nuclear genome
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