# Regulation of Milk Production by the MAPK/ERK Pathway in Water Buffalo (Bubalus bubalis): Genomic and Molecular Insights

## TL;DR

This study explores how the MAPK/ERK pathway regulates milk production in water buffalo, identifying key genes and their evolutionary relationships to improve dairy management.

## Contribution

The first comprehensive analysis of MAPK/ERK pathway genes in water buffalo, revealing conserved motifs, gene duplications, and positive selection events.

## Key findings

- Identification of 21 MAPK/ERK pathway genes in Bubalus bubalis with conserved motifs and domains.
- Discovery of seven segmentally duplicated gene pairs, with JUN-ETS1 and DUSP6-MST1 showing evidence of positive selection.
- Confirmation of genomic conservation through synteny with human orthologs and variation in gene structure.

## Abstract

The MAPK/ERK pathway plays a critical role in the regulation of milk production by controlling cellular processes such as proliferation, differentiation and survival, which are essential for lactogenesis and mammary gland function. Bubalus bubalis (Water buffalo), known for its unique physiological and ecological characteristics, serves as an ideal model to explore the evolutionary and molecular roles of MAPK/ERK pathway genes. This study presents the first comprehensive computational analysis of MAPK/ERK genes in B. bubalis, identifying 21 key genes involved in the pathway. Phylogenetic analysis clustered these genes into 13 distinct clades, such as MST1, GRB2, RAS, ETS1, JUN and FOS, and revealed close evolutionary relationships with Bos taurus and Camelus bactrianus. Structural characterization identified 10 conserved motifs, including essential domains like protein kinase, ETS and RAS, reflecting their functional significance. Gene structure analysis revealed substantial variation in exon‐intron patterns, while synteny analysis confirmed collinearity with human orthologs, indicating genomic conservation. Physicochemical analysis highlighted a broad range of molecular weights and isoelectric points, with most proteins classified as hydrophilic and thermostable. Gene duplication and selection analyses revealed seven segmentally duplicated gene pairs, with the JUN‐ETS1 and DUSP6‐MST1 pairs showing evidence of positive selection, suggesting functional divergence. These findings establish a foundational understanding of MAPK/ERK pathway genes in B. bubalis and provide valuable insights into potential targets for genetic improvement, selective breeding and sustainable dairy management strategies aimed at enhancing milk production and quality.

Genomic and molecular analyses reveal 21 MAPK/ERK pathway genes in water buffalo, highlighting conserved motifs, gene duplications and positive selection events that underpin lactation regulation. These insights provide potential targets for genetic improvement to enhance milk yield and quality.