Gene family size conservation is a good indicator of evolutionary rates

Abstract

The evolution of duplicate genes has been a topic of broad interest. Here, we propose that the conservation of gene family size is a good indicator of the rate of sequence evolution and some other biological properties. By comparing the human-chimpanzee-macaque orthologous gene families with and without family size conservation, we demonstrate that genes with family size conservation evolve more slowly than those without family size conservation. Our results further demonstrate that both family expansion and contraction events may accelerate gene evolution, resulting in elevated evolutionary rates in the genes without family size conservation. In addition, we show that the duplicate genes with family size conservation evolve significantly more slowly than those without family size conservation. Interestingly, the median evolutionary rate of singletons falls in between those of the above two types of duplicate gene families. Our results thus suggest that the controversy on whether duplicate genes evolve more slowly than singletons can be resolved when family size conservation is taken into consideration. Furthermore, we also observe that duplicate genes with family size conservation have the highest level of gene expression/expression breadth, the highest proportion of essential genes, and the lowest gene compactness, followed by singletons and then by duplicate genes without family size conservation. Such a trend accords well with our observations of evolutionary rates. Our results thus point to the importance of family size conservation in the evolution of duplicate genes.

FIG. 1.

The data collation processes.

FIG. 2.

Comparisons of median Ka (filled circles), Ks (filled triangles), and Ka/Ks (open diamonds) values of human genes and their closest counterparts in chimpanzee in (A) HS/CS expansion, HS/CS contraction, and H=C=M families; and (B) the C>H>M, all CS expansion (C>H≥M), C>H=M, and H=C=M families. Error bars represent the standard errors.

FIG. 3.

The left panel compares (A) the proportions of essential genes, (C) the expression levels, (E) the expression breadth, and (G) the gene compactness (average intron/UTR length) between gene families with and without size conservation (“H=C=M” and “non-H=C=M,” respectively). The right panel (B, D, F, and H) compares the four same features in the same order between singleton gene families with size conservation (“H=C=M=1”) and multigene families with or without size conservation (“H=C=M>1” and “dup-H≠C≠M,” respectively). The P values were estimated by using the two-tailed Fisher’s exact test (A, B, E, and F), the two-tailed Wilcoxon rank sum test (C and D), and the two-tailed t-test (G and H). NS, not significant.