Homology (genetics)

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Two genes (or proteins ) are homologous to one another if they descend from a common ancestor.

If two genes in the nucleotide sequence match in more than 30% of their nucleotides in the sequence, a cause other than the common ancestry is considered unlikely; these two genes are therefore considered to be homologous. The same applies to the amino acid sequence of produced from the genes proteins , wherein the homology is assumed to be a sequence identity of over 10%.

Homology of genes does not necessarily lead to homology of organs. For example, it cannot be ruled out that homologous genes and thus also homologous proteins are found in two completely different, non-homologous tissues.

Homologous chromosomes contain the same genes in the same sequence of gene locations, but these can exist as different alleles . This means that the chromosomes of paternal and maternal origin can differ in a diploid cell.

This concept of homology must be distinguished from the homology of different organs , which is considered in phylogenetics and evolutionary theory .

Homology between genes of different species

Homology between two genes can only be determined if the sequences are not yet so far apart that the similarity between them is only as great as between two random sequences. This depends not only on the elapsed time, but also on the degree of conservation of the respective sequence. The enzymes of important metabolic pathways such as glycolysis are highly conserved:

Protein
in humans		 Identity to the protein in the organism:
Chimpanzee
(precursor
5-6 million years) 		House rat
(forerunner
100–150 million years) 		Zebrafish
(forerunner
200-300 million years) 		Lancet
fish ( preliminary
500 million years) 		Roundworm
(forerunner
800–1000 million years) 		Escherichia
coli
PFK 100% 94% 77% 63% 40% 40%
α-hemoglobin 100% 78% 53% 31% no ortholog no ortholog
insulin 98% 82% 46% no ortholog no ortholog no ortholog
EPO ± 67% 80% 36% no ortholog no ortholog no ortholog

For example, an amino acid sequence identity of 60 to 80% is customary between homologous mammalian genes , and that of 40 to 60% between homologous vertebrate genes . If the identity falls below 10% (5% corresponds to a random result), any existing homology would actually no longer be detectable. In fact, even below 30%, the existence of homology is questionable, since independent protein domains often have a certain similarity ( parallel evolution ). Other exceptions are short and tandem sequences , as the probability of a coincidental similarity is greater here.

Homology between duplicated or foreign genes

Evolution of a gene. The idealized development of a gene from an original population A into two new populations B, C. A sloping branch represents a speciation event, a horizontal line a gene duplication. Horizontal gene transfer also takes place between B and A. (Scheme: WM Fitch)

If there were only new species formation events, then there would be a corresponding gene in every other organism for every gene. Gene duplication and horizontal gene transfer can lead to additional gene copies that evolve over time with gene drift. To more clearly distinguish the homology relationships between such genes, the following terms are used: Two genes are paralogous to one another if their common precursor gene has undergone gene duplication. Two genes are orthologous to one another when their common ancestor has gone through a speciation event. They are xenologous if one of them has a horizontally transferred ancestor (see figure, B1 and C1 are orthologous to one another, B1 and B2 paralogue, A1 and AB1 xenologous).

Furthermore, one speaks of (1: n) orthology if it is sequence X in species A and sequence Y in species B and there is a sequence Z in species B which is paralogous to Y and which is directly orthologous to X. Conversely, Y and X are (n: 1) orthologues . In both of these cases, one of the species has diversified and there is a gene duplication between X and Y (see figure, B1 and C2). Finally, (m: n) orthology between X and Y means that diversification has taken place in both species and that there are therefore two gene duplications between X and Y (not shown in the figure). Correspondingly, strict orthology is referred to as (1: 1) orthology in this context . Real examples of these relationships are the ratios between individual MADS box proteins .

Gene duplication and horizontal gene transfer are the most common biological processes that increase the number of genes. The number of genes is reduced by deleting or inserting nonsense sequences.

Genetic distance

By comparing the base sequence of homologous genes, degrees of correspondence and thus genetic distances between related species can be determined. If a point in time of the last common ancestor of these two species is known, the points in time of their last common (as yet unknown) ancestors can be determined from the degree of similarity of these genes for other closely related species.

The degree of genetic match can be viewed differently in the course of a sequence alignment , which can also result in discrepancies in the reconstruction of the temporal course of different examiners with a molecular clock :

  • The fixation index is comparatively easy to use and is therefore a frequently used relative measure with values ​​between 0 (belonging to one species) and 1 (belonging to different species).
  • Nei's standard of genetic distance relates to point mutations and genetic drift .
  • Cavalli-Sforza and Edwards 1967 refers to genetic drift.
  • Reynolds, Weir, and Cockerham's 1983 refers to genetic drift.
  • Nei's D A distance relates to point mutations and genetic drift and gives particularly reliable relationships, also based on satellite DNA.

literature

  • GS Gray, WM Fitch: Evolution of antibiotic resistance genes: the DNA sequence of a kanamycin resistance gene from Staphylococcus aureus. In: Molecular biology and evolution. Volume 1, Number 1, December 1983, pp. 57-66, ISSN  0737-4038 . PMID 6100986 .
  • RA Jensen: Orthologs and paralogs - we need to get it right. In: Genome biology. Volume 2, Number 8, 2001, S. INTERACTIONS1002, ISSN  1465-6914 . PMID 11532207 . PMC 138949 (free full text).

Individual evidence

  1. ↑ Werner A. Müller, Monika Hassel: Developmental Biology. 2006, ISBN 3-540-24057-8 , p. 252. (online)
  2. ↑ UniProt
  3. ↑ a b W. M. Fitch: Homology. A personal view on some of the problems . In: Trends in Genetics . tape 16 , no. 5 , May 2000, pp. 227-231 (228) , PMID 10782117 ( Online [PDF; 115 kB ]).
  4. ↑ Klaus D. Grasser: Annual Plant Reviews, Regulation of Transcription in Plants . Volume 29. Wiley-Blackwell, 2006, ISBN 1-4051-4528-5 , pp. 37 .
  5. ↑ Masatoshi Nei, AK Roychoudhury: Sampling variances of heterozygosity and genetic distance. In: Genetics. Volume 76, No. 2, 1974, pp. 379-390. genetics.org
  6. ↑ Rike Stelkens, Ole Seehausen: Genetic distance between species predicts novel trait expression in their hybrids. In: evolution. Volume 63, No. 4, 2009, pp. 884-897. doi: 10.1111 / j.1558-5646.2008.00599.x
  7. ↑ Population Genetics IV: Genetic distances - biological vs. geometric approaches.
  8. ↑ Masatoshi Nei, Ronald K. Chesser: Estimation of fixation indices and gene diversities. In: Annals of Human Genetics. Volume 47, No. 3, 1983, pp. 253-259. doi: 10.1111 / j.1469-1809.1983.tb00993.x
  9. ↑ Jérôme Goudet: FSTAT (version 1.2): a computer program to calculate F-statistics. In: Journal of heredity. Volume 86, No. 6, 1995, pp. 485-486. jhered.oxfordjournals.org
  10. ↑ M. Nei: Genetic distance between populations. In: Am. Nat. Volume 106, 1972, pp. 283-292.
  11. ↑ LL Cavalli-Sforza, AW Edwards: Phylogenetic analysis. Models and estimation procedures. In: American Journal of Human Genetics . Volume 19, Number 3 Pt 1, May 1967, pp. 233-257. PMID 6026583 , PMC 1706274 (free full text).
  12. ↑ John Reynolds, Bruce S. Weir, C. Clark Cockerham: Estimation of the coancestry coefficient: basis for a short-term genetic distance. In: Genetics. Volume 105, No. 3, 1983, pp. 767-779. genetics.org
  13. ↑ N. Takezaki, Masatoshi Nei: Genetic distances and reconstruction of phylogenetic trees from microsatellite DNA. In: Genetics. Volume 144, 1996, pp. 389-399.