# Verification and comparison of pig, mouse, and human genome similarities: use of manual assembly and analyses

## TL;DR

This study compares pig, mouse, and human genomes, finding pigs are more similar to humans in gene and protein conservation, making them a valuable model for human health research.

## Contribution

The study provides a manual assembly of pig RNA and protein sequences to evaluate genome builds and orthology across species.

## Key findings

- Pigs are 5.0X more likely than mice to have human genes when a gene is missing in one species.
- 73.8% of pig-human orthologous proteins are conserved across all three species.
- Pigs are 2X more likely than mice to preserve human functional domains in proteins.

## Abstract

Recently there have been numerous attempts to improve the genome of the pig. Despite these efforts, there is a substantial amount of work remaining to obtain a “finished version” of the genome; analysis of incomplete versions can lead to incorrect biological interpretations. To that end, we manually assembled and annotated a non-redundant, 16,146 RNA and 15,613 pig protein sequence libraries. We used it to assess the assembly and annotation status of the 3 latest builds of the genome and to the mouse and human genomes.

Our analysis of 6,135 protein-coding genes reveals that the percentage of error-free assembled and annotated genes in NCBI and Ensembl builds 11.1 and MARC build 1.0 are 58.9, 51.7, and 47.1%, respectively. An examination of these errors revealed nine predominant sources that are detailed in the Results. Using our protein library, we determined 1:1 orthology to 16,496 mouse and 15,770 human proteins. 73.8% of these proteins were conserved among the 3 species; however, when a gene was missing from one of the three genomes, pigs were 5.0X more likely to have the human gene than mice. REACTOME, GO BP Direct, and Ingenuity Pathway Analysis functional enrichment analyses of pig-human orthologous genes revealed 8, 13, and 35 conserved pathways, and 0, 0, and 47 for human-mouse pathways, respectively. Last, we conducted an analysis of functional domain preservation for 3,465 proteins and discovered when a functional domain is missing from a protein in 1 of the 3 species, pigs are 2X more likely to have the human domain than mice.

These data strongly indicate that, overall, swine are a scientifically important intermediate species (rodent-human) for conducting scientific research on human health.

The online version contains supplementary material available at 10.1186/s12864-025-12388-x.