Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 Jan 22;99(2):803-8.
doi: 10.1073/pnas.022629899. Epub 2002 Jan 15.

Mutation rates in mammalian genomes

Sudhir Kumar  1 , Sankar Subramanian
Affiliations

Mutation rates in mammalian genomes

Sudhir Kumar et al. Proc Natl Acad Sci U S A. .

Abstract

Knowledge of the rate of point mutation is of fundamental importance, because mutations are a vital source of genetic novelty and a significant cause of human diseases. Currently, mutation rate is thought to vary many fold among genes within a genome and among lineages in mammals. We have conducted a computational analysis of 5,669 genes (17,208 sequences) from species representing major groups of placental mammals to characterize the extent of mutation rate differences among genes in a genome and among diverse mammalian lineages. We find that mutation rate is approximately constant per year and largely similar among genes. Similarity of mutation rates among lineages with vastly different generation lengths and physiological attributes points to a much greater contribution of replication-independent mutational processes to the overall mutation rate. Our results suggest that the average mammalian genome mutation rate is 2.2 x 10(-9) per base pair per year, which provides further opportunities for estimating species and population divergence times by using molecular clocks.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Distribution of the number of fourfold-degenerate sites in the human-mouse orthologous genes. The average number of fourfold-degenerate sites from 3,722 genes of human-mouse comparison is 245, which is 15.7% of the average cDNA length (1,568).
Figure 2
Figure 2
(a) Proportion of genes rejected for 15 mammalian pairs using the disparity index test in testing the null hypothesis of homogeneity of substitution patterns in fourfold-degenerate sites at a 5% significance level (26). The total number of genes examined is shown in parentheses next to the name of the species pair; the number of genes rejected is shown next to the corresponding bar. (b) Scatter plot showing the relationship of ΔGC4 (GC content difference at fourfold-degenerate sites in orthologous sequences) with p4 (proportion of fourfold-degenerate sites with A/T ↔ G/C difference) for genes passing (black) and failing (red) the disparity index test. Green markers show the expected relationship of ΔGC4 calculated from sequence length and p4 for each gene by using equation 10 in ref. . (c) Overestimation of evolutionary distance caused by genes evolving with heterogeneous patterns of evolution for seven representative mammalian pairs. Open bars show the estimate of average distance from all genes passing the homogeneity test (26, 27). Dark bars show the average distance for the rejected genes (heterogeneous).
Figure 3
Figure 3
(a) A histogram of the neutral evolutionary distances estimated by using fourfold-degenerate sites of 2,019 human and mouse genes (mean = 0.466 and variance = 0.035; two outliers were removed from each tail). The normal distribution curve is drawn by using the observed mean and the expected variance under the null hypothesis of uniform neutral mutation rate among genes. (b) The distribution of evolutionary distances estimated from genes of varying sequence lengths.
Figure 4
Figure 4
Average differences in neutral evolutionary distances using human-mouse comparison (Δd4) were plotted for gene pairs located within 0.5 (a) and 0.1 Mbp (b). (c) Average neutral evolutionary distances (d4) from the genes located within a human-mouse conserved segment were plotted corresponding to their position on the human chromosomes. The x axis refers to the starting location of the conserved segments in a super chromosome where all 22 autosomes were concatenated in order from head to tail. A total of 108 conserved segments, each containing a minimum of five genes, were used. The horizontal line indicates the average d4 computed by using all 1,901 genes.
Figure 5
Figure 5
Accumulation of neutral substitutions over time (million years) in diverse mammalian species. The average distance per lineage is plotted for inter- and intraordinal comparisons by using, respectievely, molecular data-based (a) and fossil-based (b) time estimates reported previously. Linear regression produced a rate of 2.22 × 10−9 substitutions per site per year million years ago (r = 0.97, n = 43) for the molecular data and 2.61 × 10−9 substitutions per site per year (r = 0.92, n = 33) for the fossil data. The divergence time estimates (million years ago, Mya) from molecular data (, , –43)/fossil records (–46), and the number of fourfold sites/genes used were: human-chimpanzee (5.5/5.5, 6,302/33), human-gorilla (7/–, 3,605/23), human-orangutan (8/–, 4,329/30), chimpanzee-gorilla (7/–, 1,674/13), chimpanzee-orangutan (8/–, 1,497/10), gorilla-orangutan (8/–, 1,936/15), cercopithecidae-hylobatidae (23/20, 1,290/10), hominidae-hylobatidae (15/–, 2,321/19), cercopithecidae-hominidae (23/20, 38,128/231), catarrhini-platyrrhini (47/37, 8,194/54), cetacea-ruminantia (60/53, 955/8), cetacea-suina (60/53, 682/10), ruminantia-tylopoda (67/53, 736/5), ruminantia-suina (65/53, 30,063/204), bovinae-caprinae (20/20, 24,474/158), bovoidea-cervoidea (23/20, 1,765/16), canidae-felidae (46/37, 5,651/41), gerbillinae-cricetinae (66/–, 1,172/11), gerbillinae-murinae (66/–, 2,605/24), murinae-cricetinae (66/–, 52,043/264), mus-rattus (41/–, 486,306/2,139), primates-carnivora (95/–, 49,267/266), primates-cetartiodactyla (95/–, 179,032/985), primates-perissodactyla (95/–, 11,593/75), primates-lagomorpha (91/–, 54,670/260), primates-hystricognath rodents (109/–, 18,292/110), primates-sciurognath rodents (115/–, 543,962/2,708), cetartiodactyla-carnivora (83/–, 24,086/160), cetartiodactyla-perissodactyla (83/–, 9,188/75), cetartiodactyla-lagomorpha (92/–, 30,465/175), cetartiodactyla-hystricognath rodents (109/–, 10,227/72), cetartiodactyla-sciurognath rodents (115/–, 119,345/756), carnivora-perissodactyla (74/–, 5,364/44), carnivora-lagomorpha (92/–, 9,498/58), carnivora-hystricognath rodents (109/–, 4,986/31), carnivora-sciurognath rodents (115/–, 28,644/191), perissodactyla-lagomorpha (92/–, 4,131/34), perissodactyla-hystricognath rodents (109/–, 1,779/18), perissodactyla-sciurognath rodents (115/–, 7,843/60), hystricognath rodents-lagomorpha (109/–, 5,447/36), hystricognath-sciurognath rodents (115/–, 19,930/123), sciurognath rodents-lagomorpha (112/–, 36,672/219). In the above, a dash indicates the absence of information.
Figure 6
Figure 6
Relative evolutionary rate among different mammalian lineages. The relative evolutionary rate differences (Δr) in a gene for two lineages (say, A and B) were computed as Δr = [lA − ½(lA + lB)]/½(lA + lB), where lA and lB are the least-squares estimates of the branch lengths leading to the two lineages using the average distances between species/groups A and B and their distances with the outgroup(s). Δr was computed for each gene, and the mean value taken over all genes for groups A and B. Negative values indicate that group B is evolving faster than group A. Only the genes passing the disparity index test were used in this analysis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kimura M. The Neutral Theory of Molecular Evolution. Cambridge, U.K.: Cambridge Univ. Press; 1983.
    1. Nei M, Kumar S. Molecular Evolution and Phylogenetics. New York: Oxford Univ. Press; 2000.
    1. Li W-H, Tanimura M. Nature (London) 1987;326:93–96. - PubMed
    1. Britten R J. Science. 1986;231:1393–1398. - PubMed
    1. Wolfe K H, Sharp P M, Li W-H. Nature (London) 1989;337:283–285. - PubMed

Publication types

LinkOut - more resources