Evolutionary Novelty: Get Milk?

The "Got Milk?" slogan has to be one of the most often mimicked ads of all time.  I did a quick search, and found the figure above, apparently compiled by the milk folks themselves.

So, how did animals "Get Milk" in the first place?  In other words, how did this novelty originate during evolution?

A new paper published by Lemay et al in Genome Biology has taken advantage of the recently completed genome sequence of the bovine, Bos taurus, and has begun to address this very question.

Although I am not a mammalian biologist (meaning I don't study mammals, despite being one myself), this is the third mammalian novelty I have highlighted here (see also placenta and hair).  Mammalian genome biology is ahead of other animal groups, for obvious reasons.  All my mammalian novelty posts tell a common story: the building blocks of complex biological features pre-date the origin of the integrated traits themselves.  What I wrote for hair, can also apply to milk and mammary glands:

"Just ten years ago, results ... clarifying the molecular components of trait evolution were rare, but they have become common now that genome sequences are available for many species. Before we had some idea of gene function, and before genome sequencing, scientists could only examine one level of biological organization – the trait (hair [milk] in this case). And that could only get science so far. In the case of hair [milk], it mainly got science as far as Figure 1, which leads to the inference that hair [milk] evolved a bit before the common ancestor of living mammals. But “hair [milk]” is not one thing. It is a complex of building blocks, including structural genes (like [casein]) and developmental processes. Today, scientists can decompose a trait, like hair [milk], into its components and study the evolutionary history of each part separately, tracing the parts through various genomes."

Figure 1 is here, again, replace hair with "milk".

I learned many amazing things about the genomics of milk and mammary glands from the Lamay et al paper.

• Some 6000 genes are considered "mammary related" and are found on all the bovine chromosomes.  There are 197 unique milk protein genes!
• Compared to non-mammary genes, mammary genes are more commonly present in all mammal genomes studied.  This indicates that mammary genes are evolving more slowly and may be lost less often than other genes.  This could indicate purifying selection owing to the importance of lactation for mammalian life history.
• Milk does vary a lot among species - some babies need more fat or a bigger immunity boost, depending on the lifestyle of the species.  Variation tends to be caused by variation in number of gene duplicates, but not in the sequence of the milk proteins themselves.  One explanation for milk variation could be the levels of expression of different genes (regulatory variation).
• Mammary genes are found together in the genome.  Also milk proteins are found along with mammary genes in the genome.  This could indicate that these clusters are expressed/regulated together as groups.
• The genes expressed in milk fat globule secretion have similarity with other secretory organs.

This final result suggests that mammary glands might be considered "duplicates" (paralogs in molecular evolution parlance) of other secretory organs.  It reminds us that traits do not come from nothing.  Some designer did not shoot a lightening bolt into the first mammal, imparting it with mammary glands and milk. Furthermore, natural selection did not modify lactation genes to perfection, thereby erasing their history.  These traits, like all other traits, evolved from existing building blocks, duplicating and recombining them to form something new.  The evidence for common descent is strong and it is deep.  

As the authors wrote about lactation:

"the ontogeny of the mammary gland [may have] occurred by co-opting existing structures and developmental pathways.  Lactation may be less than 200 million years old, but its biological roots are far more ancient."

Reference
Lemay, D., Lynn, D., Martin, W., Neville, M., Casey, T., Rincon, G., Kriventseva, E., Barris, W., Hinrichs, A., Molenaar, A., Pollard, K., Maqbool, N., Singh, K., Murney, R., Zdobnov, E., Tellam, R., Medrano, J., German, J., & Rijnkels, M. (2009). The bovine lactation genome: insights into the evolution of mammalian milk Genome Biology, 10 (4) DOI: 10.1186/gb-2009-10-4-r43

Evolutionary Novelty: Mammalian Placenta

For me one of the most visceral confirmations of the common descent of humans and other mammals came while witnessing the birth of my children. Having grown up on a small farm, I have vivid memories of the birth of kittens, lambs, and goats; and after the births of my children, I was struck by the similarity of human placenta and umbilical cord to those of other mammals.  Given common descent, how did something as complex as the mammalian placenta originate in the first place? The answer, according to research published last summer in Genome Research, involves the evolutionary mechanisms of co-option and gene duplication.

Fig 1.  For me, witnessing the birth of goats, humans, kittens, and sheep - and especially umbilical cords and placentas, was a visceral re-enforcement of the scientific fact of the common ancestry of eutherian mammals.

Mammalian placentas can be considered an evolutionary novelty, like light sensitivity, hair and animal photosynthesis.  Like these other traits, a placenta is not one thing, but a collection of many structural and functional components.  We know that placentas are present in "Eutherian" mammals, but absent in marsupials, monotremes, and most non-mammals.  Therefore, based on simple parsimony, placentas originated prior to the common ancestor of eutherians.  This presents us with a null hypothesis, that components of placentas also originated at the same time.

Figure 2 - Mammal phylogeny.  Only Eutherians have placentas.  Monotremes lay eggs, and marsupials carry babies in a pouch.  Did all the components of placentas also originate with eutherians?

Research published last summer by Knox and Baker investigated the timing of the evolutionary origins of genes expressed in mouse placentas.  Since scientists have determined the sequence of all genes of the mouse genome, placental expression of all those genes could be investigated simultaneously using microarray technology.  The genes expressed in early development of mouse placentas have ancient origins.  In contrast, the genes expressed later during the development of mouse placentas have much more recent evolutionary origins.  Here, the authors define the origins of genes to be related to when the last time was they were duplicated.

When the genes expressed in a structure originated before the structure itself, we can consider this a co-option event: Genes used for other purposes are incorporated (co-opted) into the new structure.  Given common ancestry of all genes and organisms, it should not be surprising when we demonstrate co-option.  Nevertheless, there are not many cases where comprehensive gene expression within a structure has been studied in the context of evolution.  In the case of placentas, early development involves rapid growth of tissue, and deploys many genes involved in cell proliferation.  Cell proliferation and the genetic machinery for accomplishing this is conserved in evolution.  In the case of placentas, instead of re-inventing a new way of proliferating cells, or instead of duplicating cell proliferation genes especially for use in the placenta, existing genes were deployed in a new context.  This can be thought of as co-option.  An observation further consistent with co-option is that egg-laying relatives of eutherians use a membrane in eggs for oxygenation that may be similar to placentas.

Unlike the genes in early development of placentas, genes expressed later in placental development tend to be recently duplicated.  To test whether or not recent duplication of late expressed placental genes was unique to mice, the authors also examined genes expressed in human placentas.  Here again, many human placental genes were recently duplicated.  The authors suggest that the diversity of placental forms may in part be due the expression of recently duplicated genes. 

The visceral re-enforcement of common ancestry I felt when seeing a human placenta and umbilical cord extends to the genes used in developing placentas, which themselves have ancient origins, and are shared across many organisms.

Reference
K. Knox, J. C. Baker (2008). Genomic evolution of the placenta using co-option and duplication and divergence Genome Research, 18 (5), 695-705 DOI: 10.1101/gr.071407.107

Evolutionary Novelty: Hair

Mammals have hair but no other animals do. As such, hair is a clear evolutionary novelty, present in one group but absent in all others. In my macroevolution course (EEMB 102), I use hair as a clear character that can be used in phylogenetics. Hair groups all mammals to the exclusion of other organisms. In systematics jargon, hair is therefore a “synapomorphy”, grouping mammals together.

We can map the trait of hair on a family tree of animals. From this perspective, we can infer that the ancestor of all mammals very likely had hair, but that the ancestor of sauropods (birds, reptiles, and mammals) lacked hair. Therefore, hair originated prior to the common ancestor of all mammals.



Figure 1 – Hair originated before mammals, but after the common ancestor of birds, reptiles and mammals. Grey ellipse (hard to see except as a broken branch, I'd fix it but I'm too lazy) is the origin of hair keratin protein.



So where did hair come from - how did this evolutionary novelty evolve? A new paper by Eckhart et al in PNAS [link] provides evidence that the building blocks of hair pre-date the origin of hair itself. Namely, they found alpha-keratin (“hair keratin”) proteins are encoded in the genomes of chickens and the green anole lizard. In the green anole they studied, ‘hair keratin’ proteins were used in claws.


Just ten years ago, results like this clarifying the molecular components of trait evolution were rare, but they have become common now that genome sequences are available for many species. Before we had some idea of gene function, and before genome sequencing, scientists could only examine one level of biological organization – the trait (hair in this case). And that could only get science so far. In the case of hair, it mainly got science as far as Figure 1, which leads to the inference that hair evolved a bit before the common ancestor of living mammals. But “hair” is not one thing. It is a complex of building blocks, including structural genes (like keratin) and developmental processes. Today, scientists can decompose a trait, like hair, into its components and study the evolutionary history of each part separately, tracing the parts through various genomes.

What do we expect for the evolution of hair’s components? Figure 1 suggests that “hair” and all its components arise at the same time, near the origin of mammals. The origin of “hair” on figure 1 can be considered a first-pass hypothesis for the origins of ALL the components of hair. If hair itself originated near the origin of mammals, a logical idea is that the components originated then too.

Today, we can test this first-pass hypothesis because we know some of the molecular components of hair. A particularly important part is “hair keratin”. Mutate this protein and the hair built from that mutant protein is fragile and brittle. The expectation based on figure 1 is that hair keratin proteins originated with hair itself. But the discovery of these genes in an anole indicates an earlier origin for this component. In other words, components of hair originated before hair itself. In this case the protein “hardened” by mutations to cysteine amino acids that may have functioned to molecularly harden the proteins. Since these changes were later useful in the structure of hair, they may be considered exaptations, features that originated for functions other than current utility: keratins may have hardened before that feature became useful for hair formation. [Note for scientific accuracy – the biochemistry of the anole protein has not been studied, so while it is cysteine rich, we don’t know yet if the anole protein is ‘hardened’].

This work also illustrates that in evolution, new things do not appear from nowhere [see my post Coming to Grips]. In evolution, new things come from the duplication/differential modification and recombination of existing parts. Morphologists know this, as one dominant idea about the origin of hair is that hair evolved by modification of scales. Hair keratin is not expressed in anole scales, so the scale hypothesis is not supported by the new PNAS paper. Also unfortunate for the scale hypothesis is the fact that the fossil record retains no transitional forms between scale and hair. Even though morphological relatives of hair are ambiguous, the molecular relatives in this case are clear. Hardened keratin comes as two types, which share an evolutionary relationship, and hardened keratins may share an evolutionary relationship with soft keratins, proteins that are present in numerous tetrapods, and therefore have a more ancient origin than the hard variety. In sum, keratin has an ancient heritage, and through gene duplications and differential modification, two related groups of these proteins have specialized as hair keratins. Fascinatingly, some of the hair keratin modifications pre-dated hair itself.







If you are interested phylogenetic analyses of trait evolution, and the evolutionary history of trait components, this is a common theme of research in my lab.

We’ve found:

Synaptic components are present in sponges and therefore may predate synapses. [paper] [blog]

Phototransduction components were first assembled for vision in the eumetazoan ancestor (cnidaria + bilateria), yet some components pre-date animals [blog] [blog] [paper] [paper]

See also: Red Herring Blog