The bovine lactation genome: Insights into the evolution of mammalian milk

Authors: LEMAY, DANIELLE - University Of California; LYNN, DAVID - Simon Fraser University; MARTIN, WILLIAM - University Of Colorado; NEVILLE, MARGARET - University Of Colorado; CASEY, THERESA - Michigan State University; RINCON, GONZALO - University Of California; KRIVENTSEVA, EVGENIA - University Of Geneva; BARRIS, WESLEY - Commonwealth Scientific And Industrial Research Organisation (CSIRO); HINRICHS, ANGIE - University Of California; MOLENAAR, ADRIAN - Agresearch; POLLARD, KATHERINE - University Of California; MAQBOOL, NAUMAN - Agresearch; SINGH, KULJEET - Agresearch; MURNEY, REGAN - Agresearch; ZDOBNOV, EVGENY - University Of Geneva; TELLAM, ROSS - Commonwealth Scientific And Industrial Research Organisation (CSIRO); MEDRANO, JUAN - University Of California; GERMAN, J - University Of California; RIJNKELS, MONIQUE - Children'S Nutrition Research Center (CNRC)

Submitted to: Genome Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/24/2009
Publication Date: 4/29/2009
Citation: Lemay, D.G., Lynn, D.J., Martin, W.F., Neville, M.C., Casey, T.M., Rincon, G., Kriventseva, E.V., Barris, W.C., Hinrichs, A.S., Molenaar, A.J., Pollard, K.S., Maqbool, N.J., Singh, K., Murney, R., Zdobnov, E.M., Tellam, R.L., Medrano, J.F., German, J.B., Rijnkels, M. 2009. The bovine lactation genome: Insights into the evolution of mammalian milk. Genome Biology. 10(4):R43.1-R43.18.

Interpretive Summary: Milk from different species has different nutrient content, but how these differences came about is a question yet to be answered. The recently published cow genome sequence can help to answer this question. We investigated the genes for cow proteins present in milk and proteins present in the cow mammary gland during lactation in relationship with genes from other mammals. We found that: 1) Milk and lactation genes are more similar between species than most other genes in the genome of the cow, which indicates the importance of lactation for the survival of mammalian neonates; 2) Proteins associated with nutritional and immunological components of milk differ most between mammals. This indicates that milk is tailored to the needs of the individual offspring. This will inform us about components of milk that are important for healthy growth and development of newborns. We show that differences in the composition of milk of different species are in part due to changes in sequences of the milk and lactation-related genes or the organization of the genome. However, changes in regulation of these genes are likely to play a larger role. Identification of those changes in gene regulation will be important for improvement of milk production and nutritional content of milk.

Technical Abstract: The newly assembled Bos Taurus genome sequence enables the linkage of bovine milk and lactation data with other mammalian genomes. Using publicly available milk proteome data and mammary expressed sequence tags, 197 milk protein genes and over 6,000 mammary genes were identified in the bovine genome. Intersection of these genes with 238 milk production quantitative trait loci curated from the literature decreased the search space for milk trait effectors by more than an order of magnitude. Genome location analysis revealed a tendency for milk protein genes to be clustered with other mammary genes. Using the genomes of a monotreme (platypus), a marsupial (opossum), and five placental mammals (bovine, human, dog, mice, rat), gene loss and duplication, phylogeny, sequence conservation, and evolution were examined. Compared with other genes in the bovine genome, milk and mammary genes are: more likely to be present in all mammals; more likely to be duplicated in therians; more highly conserved across Mammalia; and evolving more slowly along the bovine lineage. The most divergent proteins in milk were associated with nutritional and immunological components of milk, whereas highly conserved proteins were associated with secretory processes. Although both copy number and sequence variation contribute to the diversity of milk protein composition across species, our results suggest that this diversity is primarily due to other mechanisms. Our findings support the essentiality of milk to the survival of mammalian neonates and the establishment of milk secretory mechanisms more than 160 million years ago.