Where does milk come from?

This post was chosen as an Editor's Selection for ResearchBlogging.orgMilk comes from cows. Most of us know that. More urban readers are forgiven for thinking milk comes from supermarkets. But the the question where milk comes from has the potential to reach beyond dairy farms and breakfast tables. It could be about the origins of milk itself, millions of years ago. “Where does milk come from?” becomes “how did milk evolve?”

Milk is essential for the survival of pups, cubs and calves around the world. Young mammals can gain weight and grow on a diet of milk alone because it is rich in proteins, vitamins, calcium and saturated fats. But milk has not always been this nutritious.

A hatching corn snake. Notice the leathery texture of the egg.

Our mammalian ancestors started giving milk when they were still laying yolky eggs. The shells of these eggs weren’t hard and calcified like the eggs of birds. They were soft and had a parchment-like eggshell instead, much like the eggs of lizards and snakes. If you would study such eggshells under a microscope, you would see that their surface is covered with millions of narrow pores. If it is too hot or dry, water evaporates through these pores, putting the eggs at risk of drying out.

Snakes and lizards prevent this from happening by laying their eggs in a moist soil. But early mammals solved this problem in a different way, Olav Oftendal thinks. He suggests that lactation didn’t evolve to nourish, but to drench. Fluids secreted through the skin of ancestral mammals could have protected the eggs from drought and desiccation. If true, the first ‘milk’ was not that milky at all: think twice before mixing Triassic milk with your cornflakes.

The eggshell pores forced the ancient mammals to look for answers. When these answers were found, the advantages of an passable eggshell could begin to be exploited. Through the pores, extra nutrients added to the moistening fluid reached the developing hatchling inside the egg. New opportunities awaited in this twilight zone between moist and milk. Eggs could grow smaller, because the yolk no longer need to provide every single nutrient the embryo needed. Young animals could delay their development, since they no longer needed to hatch as miniature adults.

But that’s running ahead of the story. There are genes that can tell us more about how our ancestors switched from yolk to milk.

Electron microscope picture of a milk micelle.

Caseins
Caseins are the most abundant proteins in milk. They come in two forms. One type binds calcium, the other one is insensitive to calcium. When you bring thousands of these caseins together, they self-assemble into a soluble micelle. Micelles look a bit like little balls of hair. The ‘hairs’ are really the tails of caseins that are sticking outwards. The calcium-insensitive caseins stabilize the micelle, but it is thanks to the calcium-binding caseins that micelles are loaded with calcium. If milk contained the same concentration of calcium without the micelles, the calcium wouldn’t remain soluble and precipitate.

From cows to kangaroos, all mammals have casein genes. And in every mammalian genome, the caseins are surrounded by closely related genes. The technical name for this family of genes is ‘secretory calcium-binding phosphoprotein family’. Or SCPP family, for friends. As the family name implies – most of the SCPP family members can bind calcium. The SCPP family is old. One of its oldest family members, SPARCL1, uses calcium to mineralize our bones. It evolved more than 400 million years ago and can be found in all creatures with a calcified skeleton, such as bony fish, reptiles, birds and mammals.

The SPARCL1 gene was duplicated again and again. These carbon copies of SPARCL1 were free to evolve new functions. Some copies now mineralize other tissues, such as the enamel of our teeth. Kazuhiko Kawasaki and his colleagues from Penn State University have shown that milk caseins evolved from such tooth mineralizing SCPPs. One of the recent reconstructions by Kawasaki revealed that the different types of caseins also evolved from different types of tooth mineralizing SCPPs.

The evolution of the SCPP proteins, from the earliest tetrapods to the almost-mammalian synapsids. The SCPP family has been evolving fast: genes were duplicated and lost many times. The calcium-binding caseins are CSN1/2, the calcium-insensitive casein is CSN 3.

Vitellogenins
When something is gained, something else is lost. A recurring pattern in evolution. While caseins were born from tooth genes, the vitellogenin family became extinct.

Vitellogenins are the defining proteins of egg yolk. In all species that lay eggs (from insects to amphibians), vitellogenins provide the nourishment that developing embryos inside an egg need. Ancient mammals were no exception to this rule. They had three different vitellogenin genes, like modern birds and reptiles do.

But as milk became more nutritious, the egg yolk of pre-mammalian eggs became less and less important. When they were no longer needed, the vitellogenin genes were inactivated one by one. The remnants of these vitellogenins can still be found in our genomes today. They are the broken relics of a time when our distant ancestors still laid eggs. Still recognizable, but without a function for many millions of years.

While the birth and death of families of genes make for good dramatic narrative, it is important to realize that milk evolved gradually. There is no single point in time when milk, or mammals for that matter, sprung into existence. From pelycosaurs, to therapsids, to cynodonts: mammal-like creatures have around for millions of years.


Hatching corn snake by Jonathan Crowe.
Micelle picture from second reference.
SCPP evolution from third reference.

 


Oftedal OT (2002). The origin of lactation as a water source for parchment-shelled eggs. Journal of mammary gland biology and neoplasia, 7 (3), 253-66 PMID: 12751890

 

DALGLEISH, D. (2004). A possible structure of the casein micelle based on high-resolution field-emission scanning electron microscopy International Dairy Journal, 14 (12), 1025-1031 DOI: 10.1016/j.idairyj.2004.04.008

Kawasaki K, Lafont AG, & Sire JY (2011). The evolution of milk casein genes from tooth genes before the origin of mammals. Molecular biology and evolution PMID: 21245413

Brawand D, Wahli W, & Kaessmann H (2008). Loss of egg yolk genes in mammals and the origin of lactation and placentation. PLoS biology, 6 (3) PMID: 18351802


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9 comments to Where does milk come from?

  • echidna

    From cows to kangaroos, you say. Can you tell us more about the platypus and echidna, which are the only mammals extant that both lay eggs and give milk?

  • Caseins can also be found in monotremes (platypus, echidna and others). There are some differences between caseins of monotremes and other caseins though. I believe their ‘calcium-insensitive’ caseins can still bind calcium, for example.

    Platypus and echidna eggs could help in verifying Oftedal’s hypothesis. If milk really provided ancestral eggs with nutrients through the pores in the eggshell, you’d expect something similar to happen in monotreme eggs. Sadly “.. it is not known if monotremes secrete milk during egg incubation, or if they apply milk secretions to their eggs.” (Oftedal).

    Monotremes haven’t lost all the vitellogenin genes, like other mammals have. They still have one functional copy (not that researchers could only detect two vitellogenin genes in the platypus genome: one active, one inactive). This ‘intermediate’ loss of vitellogenins could reflect the smaller size and less yolk in mononotreme eggs, compared to eggs from reptiles and birds. But that’s speculation on my part.

  • LOL my first answer to that question was “milk comes from soya!” That’s what you get from living with someone whose lactose-intolerant :p

    Milk is really complex stuff. We did have brief thoughts about trying to get bacteria to produce it at the beginning of the iGEM project (as an alternative to baby formula) but it turned out to have waaaay too many components, several of which were not entirely certain and required background eukaryote synthesis pathways.

  • Question

    Very interesting. But please let me know if i got it right. So the research suggests that, caseins started taking place of vitellogenins in the process of mammal evolution. Because eggs were soft and porous, milk could actually penetrate the egg shells, so as the milk became more and more nutritious, it has taken over the task to feed the fetus inside the egg, instead of the egg yolk.

    Sorry for my ignorance if i got it all wrong, i am not a scientist, just a geek.

    The vitellogenin producing genes that we still posess is another slap on the face of creationists. :)

    • That’s a perfect summary!

      Remember that milk and egg yolk consist of many more proteins and molecules than caseins and vitellogenins. So while caseins and vitellogenins are indicative of the trends of milk becoming more and yolk becoming less nutritious, they didn’t replace each other on a one-to-one basis.

  • Question

    OK here is another one. Could that theory also shine light on why males of mammal speciels also have breasts ? May be it was the job of both sexes to incubate and moisturise the eggs back then. As far as i know, even today, there are species that males, as much as females, are part of the incubation process.

    • That’s an excellent question!
      Darwin himself tried to find an answer as far back as 1875:

      It may be suggested, as another view, that long after the progenitors of the whole mammalian class had ceased to be androgynous, both sexes yielded milk, and thus nourished their young; and in the case of the marsupials, that both sexes carried their young in marsupial sacks
      Charles Darwin, Chapter 6, Descent of Man

      The literature on this subject is sparse though – there are some articles on male lactation in mammals such as fruit bats.

      My personal feeling is that males have nipples and breasts simply because women have them. Developmentally, it is sometimes easier to install some ‘plumbing’ early on (mammary glands, nipples), before the embryo becomes entirely male or female. Nipples aren’t disadvantageous for men – so they’re not selected against.