Few Nuclear-Encoded Mitochondrial Gene Duplicates Contribute to Male Germline-Specific Functions in Humans

Abstract

Most of the genes encoding proteins that function in the mitochondria are located in the nucleus and are called nuclear-encoded mitochondrial genes, or N-mt genes. In Drosophila melanogaster , about 23% of N-mt genes fall into gene families, and all duplicates with tissue-biased expression (76%) are testis biased. These genes are enriched for energy-related functions and tend to be older than other duplicated genes in the genome. These patterns reveal strong selection for the retention of new genes for male germline mitochondrial functions. The two main forces that are likely to drive changes in mitochondrial functions are maternal inheritance of mitochondria and male-male competition for fertilization. Both are common among animals, suggesting similar N-mt gene duplication patterns in different species. To test this, we analyzed N-mt genes in the human genome. We find that about 18% of human N-mt genes fall into gene families, but unlike in Drosophila , only 28% of the N-mt duplicates have tissue-biased expression and only 36% of these have testis-biased expression. In addition, human testis-biased duplicated genes are younger than other duplicated genes in the genome and have diverse functions. These contrasting patterns between species might reflect either differences in selective pressures for germline energy-related or other mitochondrial functions during spermatogenesis and fertilization, or differences in the response to similar pressures.

Keywords: gene duplication; human; male-biased expression; nuclear-encoded mitochondrial genes.

Fig. 1.—

Heatmap of gene expression for N-mt duplicated genes from Drosophila (left) and human (right). Only new duplicated N-mt genes (i.e., genes for which the child status was confirmed) are shown on the Y axis ranked by their Z score for testis. Only adult tissues are shown on the X axis (27 out of 32 tissues for human, and 17 out of 27 tissues for D. melanogaster). Raw expression data was transformed into Z scores to show the extent of tissue-biased expression. Expression levels higher/lower than the mean expression across all tissues have positive/negative Z scores as indicated by blue/pink colors.

Fig. 2.—

Expression pattern of N-mt duplicated genes in human and D. melanogaster. Tissue-biased N-mt duplicated genes in human show expression bias in multiple tissues while all tissue-biased genes in D. melanogaster are testis biased.