Thursday, 23 December 2010

Johnald's Fantastical Daily Link Splurge

Johnald's Fantastical Daily Link Splurge

Early Reports From the ‘Dark Matter’ of the Genome

Posted: 22 Dec 2010 03:09 PM PST

A collection of new studies on the genomes of two model organisms has moved the frontiers of biology forward, and hints at methods that may someday make real the long-promised, as-yet-unfulfilled genomic revolution.

Published in Nature and Science, the studies go far beyond the level of genes that code for proteins, which represent just a small fraction of all genes and an even smaller fraction of all DNA in the genome.

Once thought to contain the blueprint of life, protein-coding genes were just the most visible ink in a parts list. The new studies both expand that list and begin to show how the parts are arranged — and how they interact.

"It's become very clear that DNA sequences are just a building block. They don't explain higher-order complexity," said Peter Park, a Harvard University bioinformaticist and co-author of one of the Nature studies. "People are sequencing all these genomes, but it doesn't actually tell us about the activities of the cell."


Park is a contributor to modENCODE, short for the model organism ENCyclopedia of DNA Elements, a massive international collaboration of dozens of institutions and hundreds of researchers. They study an alphabet soup of transcription factors, messengers, regulators and other types of DNA that interact with protein-coding genes to sustain the processes of life.

It's an effort that few people thought necessary a decade ago, when the Human Genome Project's near-completion was marked by a White House ceremony where President Clinton announced that "it will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases," and that "humankind is on the verge of gaining immense, new power to heal."

That may very well still happen, but not on the timetable that many scientists expected. With some exceptions, such as breast-cancer-susceptibility mutations and single-gene conditions like Huntington's disease and Marfan syndrome, identifiable genetic variation has done relatively little to explain disease or development. Promising pathways and mechanisms have been flagged and are now being explored, but understanding is slow in coming.

Over the past two years, a series of high-profile genome-wide association tests (comparisons of variation at genomic "hotspots" in thousands of people) suggested new pathways. But they didn't provide anticipated explanations for disease, and the limitations of standard genomics entered the scientific mainstream. Discussions of "missing heritability," or the roughly 95 percent of disease risk that's heritable to the naked eye but can't be tagged in a sequencer, appeared in the New England Journal of Medicine and Nature.

All this represented not a failure, but a dawning realization of just how extraordinarily complicated each genome is. As the process of learning builds on the Human Genome Project's early steps, researchers are taking fine-grained looks at each genome's full DNA and chemical components, then trying to understand how all these work together at different scales, from molecules to cells to whole organisms.

"The goal of modENCODE is to identify all the functional elements in the genome, and to understand what the genome is doing, which is the next step beyond knowing the sequence," said Brenton Graveley, a University of Connecticut development biologist.

An overview of datasets for the fruit fly section of modENCODE. Image: Science

In one of the Nature papers, Graveley and dozens of other researchers used new DNA-sequencing techniques to take a base-by-base look at the fruit fly genome, hoping to identify pieces missed in earlier studies. (He compared earlier examinations to "going into a grocery store and not thinking bananas were a fruit, because you the only fruit you know are apples.")

They identified 2,000 previously unknown genes, which now account for one-eighth of the fruit fly's genome. Beyond that, they identified more than 100,000 new elements, or molecules that aren't genes but may still have function in the genome. In fruit flies, about 40 percent of the genome fits this description. In humans, it's closer to two-thirds.

The second Nature study looked at non-DNA chemical "information" on the genome, which is made from chromatin: DNA wrapped around proteins called histones, and combined with still more proteins, all of which affect how the DNA works.

This approach is known from epigenetics (epi means outside) but the new examination was unprecedentedly thorough, looking at dozens of epigenetic factors, at every single DNA base. The resulting "chromatin landscape" revealed regions that once seemed dead, but now appear involved in gene regulation. It's also just a beginning.

"At each location on the sequence, we can measure all these different attributes of chromatin. There are hundreds of attributes, and we only now know what a couple of dozen do," said Park. "How these marks translate into gene regulation is important. Right now we just see correlations. We don't necessarily understand the mechanisms behind this."

A streamlined representation of the interplay between transcription factors and microRNAs in the roundworm. Image: Science

Such mechanisms, and how genetic elements and regulatory layers interact as cells function and organisms develop, is the province of the two Science papers. These provide network-level analyses, or "wiring diagrams," of the fruit fly and roundworm, said Yale University bioinformaticist Mark Gerstein, co-author of the roundworm paper.

Gerstein's specialty is network structure. In other research he's compared the characteristics of gene networks between organisms, and even between bacteria and computer operating systems. That work has hinted at the importance of network structure to producing wildly different organisms from common genetic components. (Humans and mice famously share almost the same set of genes.)

"Previously, people had looked at transcription factor networks in E. coli and yeast, but nobody had ever looked at this scale of network in an animal," said Gerstein. "You can start to see patterns: a microRNA that regulates a transcription factor, transcription factor that regulates microRNA, a feedback loop. We observe many of these."

In a commentary accompanying the Science papers, University of Edinburgh geneticist Mark Blaxter likened modENCODE to the Large Hadron Collider, investigating the nature of the genome's "dark matter."

"It is not currently possible to compute an organism from its genome," he wrote, but the modENCODE work will "bring this goal closer."

Despite the volume of the studies, joined by 17 more studies released in tandem in the Journal of Genome Research, the modENCODE work is just beginning. "We're looking at a vast amount of data. We're just scratching the surface," said Park. Future studies will look in greater detail at different tissue types and stages of development.

The modENCODE work is also considered a warm-up for a similar project in humans, called ENCODE. It should generate comparable findings in the next two years.

"There remains much to be discovered to be discovered even about organisms that are as exhaustively studied as the fruit fly," said Graveley. "In organisms like humans, there are undoubtedly many, many more mysteries to be uncovered."

Top image: A visualization of physical chromosome arrangement (left) and histone modification readings (right) at a given DNA base location (the green dot).
Peter Park/Harvard University.

See Also:

Citations: "Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project." By Mark B. Gerstein, Robert H. Waterston et al. Science, Vol. 330 No. 6012, Dec. 24, 2010

"Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE." The modENCODE Consortium, Sushmita Roy, Manolis Kelis et al. Science, Vol. 330 No. 6012, Dec. 24, 2010.

"Revealing the Dark Matter of the Genome." By Mark Blaxter. Science, Vol. 330 No. 6012, Dec. 24, 2010.

"Comprehensive analysis of the chromatin landscape in Drosophila melanogaster." By Peter Kharchenko, Peter Park et al. Nature, Vol. 468 No. 7327, Dec. 23, 2010.

"The developmental transcriptome of Drosophila melanogaster." By Brenton Gravely, Susan Celniker et al. Nature, Vol. 468 No. 7327, Dec. 23, 2010.

Video: Blue Eclipse on Mars

Posted: 22 Dec 2010 01:16 PM PST

Earth isn't the only planet graced with gorgeous eclipses. On Nov. 9, the Mars rover Opportunity watched the larger of Mars's two moons, Phobos, slip quietly in front of the sun.

This movie combines 10 individual photos taken every four seconds through special solar filters on the rover's panoramic cameras. The video was made from images that were calibrated and enhanced, plus extra frames to make the movie run smoothly through the entire 32-second-long eclipse.

Phobos is too small to completely cover the sun, so Martians never get to see total solar eclipses like the one visible from the South Pacific this summer. Instead, astronomers call Phobos's journeys across the face of the sun transits or partial eclipses.

Images of these transits taken many years apart can help scientists track changes in the moons' orbits, which in turn gives information about Mars's interior.

But for some Mars explorers, like Panoramic camera principal investigator Jim Bell, the spectacle of seeing events on Mars as if we were there is just as exciting as the science the images reveal.

"It reminds me of a favorite quote from French author Marcel Proust," Bell said in a press release. "'The real voyage of discovery consists not in seeking new landscapes, but in having new eyes.'"

Video: NASA/JPL-Caltech/Cornell/Texas A&M

See Also:

Follow us on Twitter @astrolisa and @wiredscience, and on Facebook.

Fossil Finger DNA Points to New Type of Human

Posted: 22 Dec 2010 11:05 AM PST

Continued study of an approximately 40,000 year old finger bone from Siberia has identified a previously unknown type of human — one that may have interbred with the ancestors of modern-day Melanesian people.

The fossil scrap — just the tip of a juvenile female's finger — was discovered in 2008 during excavations of Denisova cave in Siberia's Altai Mountains. Anatomically, it looks like it could have belonged to a Neanderthal or a modern human. But, in an initial announcement published in April in Nature, a team of scientists led by geneticist Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology concluded the bone belonged to a distinct population of humans that last shared a common ancestor with Neanderthals and our species about a million years ago.

The new study, published by Pääbo and colleagues Dec. 22 in Nature, provides further evidence that Denisova cave was home to unique humans. The researchers analyzed genetic sequences recovered from the nuclei of cells, which offer better resolution of relationships than the mitochondrial samples used in the previous research. The Denisova DNA sequences were closest to the Neanderthals, indicating they shared a more recent common ancestor with Neanderthals than with us.


The new genetic data suggests the ancestors of the Neanderthals and Denisovans left Africa between 300,000 to 400,000 years ago and rapidly diverged. But this estimate is based on models of the rates that genes typically mutate and could be off the mark.

"The Neanderthal and Denisova population history may be roughly twice the length suggested in [the Nature] paper," said University of Wisconsin — Madison anthropologist John Hawks, who was not involved with this study. "The ancestors [of the Denisovans] might be the original "Homo erectus" dispersal from Africa."

The big question, however, is whether the Denisovans are a new species of human.

They were genetically distinct from other humans, and an upper molar tooth (above) found at the same excavation hints that these people were similar to earlier species like Homo erectus.

But this is not enough to declare a new species, especially since the same team of researchers recently found that Neanderthals likely interbred with populations of our species that moved outside Africa. Between 1 and 4 percent of the genes of non-Africans match those found in Neanderthals, making it difficult to draw the species line.

An unexpected discovery about the Denisovans further complicates the picture: Some modern-day people carry Denisovan genes. Through genetic comparisons Pääbo's team found that some people from Melanesia — an assemblage of islands off Australia's east coast, including New Guinea — share 4 to 6 percent of their genomes with the Denisovans. This probably indicates that the Denisovans interbred with anatomically modern humans despite the split between our lineages over a million years ago.

The authors of the new paper didn't go as far as calling the Denisovans a new species, and "on a biological species concept," says Hawks, "there's really no reason to regard this as a different species."

Images: 1) The molar from the Denisova cave, as seen from above and the side. Credit: David Reich et al., Nature. 2) A map of human migrations. The triangles and circles represent sampling locations of Neanderthal remains of present-day human genomes, respectively. The blue arrows trace major migration routes of anatomically modern humans out of Africa. The yellow box and star denote the correspondence between the Denisova DNA samples and the genomes of people from Melanesia. From Bustamante & Henn, Nature.

See Also:

6 Strange Fossils That Enlightened Evolutionary Scientists

Posted: 22 Dec 2010 04:00 AM PST

<< Previous | Next >>

Critics of Charles Darwin's theory of evolution often cited the fossil record's lack of creatures "caught in the act" of evolution. And though fossils had been important to the development of Darwin's evolutionary thoughts, these absences frustrated him.

Read more on strange, inspiring dinosaur fossils in an excerpt from the new book by Brian Switek, Written in Stone.

Fossils had been important to the development of Darwin's evolutionary thoughts. He had collected the bones of many strange fossil mammals from South America during his days voyaging on the Beagle and wondered if there was a connection between animals like the giant ground sloths of prehistory and the continent's modern, arboreal sloths. If sloths, armadillos and other mammals were so different in the ancient past, then obviously life was not static and could change over time.

But by 1859 when On the Origin of Species was published, Darwin had largely left paleontology behind. It was up to other researchers to find the fossil proofs of evolutionary change.

Many paleontologists agreed with Darwin that some sort of natural laws were behind the succession of different organisms through time discovered in the earth's layers. But many — if not most — were not convinced that natural selection was the driving force behind these changes.

Even so, Darwin brought the subject of evolution to the forefront of Victorian science. And with an eye toward evolution, his colleagues began to pick through the traces of ancient life for clues about how organisms changed. This is a gallery of some of the key fossil species that have both confounded and inspired scientists in their efforts to understand the history of life and, placed in context of what we know today, have confirmed Darwin's vision of a branching tree of life produced by natural selection.

Image: During his 1876 American lecture tour, T.H. Huxley used this diagram to illustrate how the limbs of dinosaurs (middle) were more similar to those of birds (left) than crocodiles (right)./Written in Stone

<< Previous | Next >>

See Also:

Book Excerpt: The Dinosaur Fossils That Changed Everything

Posted: 22 Dec 2010 04:00 AM PST

Footprints and Feathers on the Sands of Time

Humans have been finding the traces of extinct creatures for thousands of years. Unaware of their true identity, a variety of cultures have interpreted fossil footprints, shells and bones as the remnants of gods, heroes, saints and monsters. The cyclops, griffins and numerous other beings of myth and legend were not just figments of human imagination but monsters restored from the remains of creatures dead for millions of years. It was no different among the Native Americans of North America. The Tuscaroras, Iroquois, Onondagas and many other tribes had legends inspired by fossils, including the Lenape of the Delaware Valley.

Brian Switek

Science writer and research associate at the New Jersey State Museum, Brian Switek has done fieldwork on fossils in Utah, Montana and Wyoming. He is a frequent guest on the BBC and has written about paleontology for Smithsonian magazine, London Times, Wired Science and elsewhere. He is the author of the science blog Laelaps here on our Wired Science Blogs network and Smithsonian magazine's Dinosaur Tracking blog. Written in Stone is his first book.

Have a look at some of the strangest fossils in the author's gallery of strange, historically significant fossils.

At the time Europeans arrived in North America the Lenape occupied the land from northern Delaware to the Hudson Valley of New York, and in the blood-red sandstone of this range they saw three-toed, clawed footprints. According to one tale, passed down by Richard Calmet Adams, some of these were said to be the footprints of the primeval progenitor of all the great monsters of the land and sea. It was a living horror, the destroyer of all it could dig its claws into, but perished when it was trapped in a mountain pass and obliterated by lightning.

Europeans that settled in the Connecticut Valley noticed the tracks, too. While plowing his father's field in South Hadley, Massachusetts, around 1802 a young man named Pliny Moody turned up slabs of rock indented with weird footprints. At least one of these curiosities was appropriately put to use as a doorstep, and visitors to the Moody farm sarcastically remarked that the Pliny's family must have raised some hearty chickens if they left footprints in solid stone. The physician Elihu Dwight, who later bought the slab, had a different interpretation. To him the tracks were made by Noah's raven when the biblical Deluge subsided.

Such tracks were hardly unique. The abundant three-toed footprints were often called "turkey tracks" (although many indicated turkeys bigger than a full-grown human), and a cache of the impressions were discovered by laborers quarrying flagging stones near Greenfield,Massachusetts, in 1835. These were brought to the attention of the local physician James Deane, who knew they were not made by antediluvian poultry or biblical birds. Just what had created them, though, Deane could not say, and so he contacted Amherst geology professor Edward Hitchcock and Yale academic Benjamin Silliman for their opinions.

Hitchcock was initially skeptical of Deane's claims. Some mundane geological phenomenon could have produced tracklike marks, the professor cautioned, but Deane was adamant that the footprints were genuine. Deane sent Hitchcock a cast of one of the footprints to support his case, and despite his doubts Hitchcock was intrigued. Hitchcock soon set out to have a look at the Greenfield tracks for himself and found that Deane was right. The impressions were the footsteps of ancient creatures that had trod the Connecticut Valley long before humans had settled there.


One of the many track-bearing sandstone slabs that enthralled Edward Hitchcock.

Hitchcock became enthralled by the tracks. He collected and purchased as many as he could. He fancied himself a scientific pioneer. Although Deane was also researching the tracks, Hitchcock was the first to publish on them in an 1836 issue of the American Journal of Science. There was a variety of footprint types, each given a unique binomial name to indicate a different species, but the three-toed ones were some of the most remarkable. They ranged from giant tracks over seventeen inches long to tiny impressions less than an inch from front to back. A few large slabs even showed the strides of the animals, and the only reasonable conclusion was that they had been made by birds that flocked along the ancient shoreline. "Four out of five, I presume, would draw this conclusion at once," Hitchcock noted, and he thought that the tridactyl footprints were made by extinct equivalents of storks and herons that strode along the banks of an ancient lake or river.

Hitchcock was deeply inspired by the varied assemblage of birds that had once lived in the Connecticut Valley, and he attempted to do justice to his fascination in the anonymously published poem "The Sandstone Bird." In the geologist's verse, science is placed in the guise of a sorceress who conjures up the most majestic of the primeval birds:

Bird of sandstone era, wake!
From thy deep dark prison break.
Spread thy wings upon our air, Show thy huge strong talons here:
Let them print the muddy shore
As they did in days of yore.
Pre-adamic bird, whose sway
Ruled creation in thy day,
Come obedient to my word,
Stand before Creation's Lord.

So restored, Hitchcock's fictional bird could only lament the dismal state of the modern world. The earth was cold and the impressive giants it knew so well were all gone. Even the trees were so Lilliputian that the dinosaur "Iguanodon could scarce here find a meal!" The haughty bird could not stand the sight of what had become of its home.

. . . all proclaims the world well nigh worn out,
Her vital warmth departing and her tribes,
Organic, all degenerate, puny soon,
In nature's icy grave to sink forever.
Sure 'tis a place for punishment designed,
And not the beauteous happy spot I loved.
These creatures here seem discontented, sad:
They hate each other and they hate the world,
I can not, will not, live in such a spot.
I freeze, I starve, I die: with joy I sink,
To my sweet slumbers with the noble dead.

The sullen bird was then swallowed up by the earth, leaving the geologist with no evidence to prove what he had seen. Hitchcock was in a similar bind. No skeleton had been found to reveal the true form of his birds. Storks and herons provided fair analogs, but even the largest of the living wading birds was puny compared to the birds that made the largest fossil tracks. Without skeletons, Hitchcock could only guess what they looked like.

At the same time that Hitchcock was researching the Connecticut Valley tracks, Richard Owen was examining a strange chunk of bone from New Zealand. It was said to have belonged to an enormous eagle, but Owen took it to be part of the femur of a gargantuan, ostrichlike bird he called Dinornis (commonly known as the moa). From the osteological scrap he reconstructed an entire skeleton, and it was later proven to be correct when more remains of the flightless birds were found. Owen had raised a giant bird from the dead, and it provided the perfect proxy for the sandstone birds.

For Hitchcock, though, there were more than just scientific lessons to be learned from the tracks. What he saw in the fossil record spoke of God's benevolence, and he expounded upon this belief as a Congregationalist pastor and professor of natural theology at Amherst. (Part of his inspiration for collecting so many tracks was to build a testament to God's glorious works in nature.) He was astonished by the vast array of stupendous creatures that crawled, swam, flew, and dashed over the surface of the earth in time immemorial. Though facts from the geological strata were shaking the foundations of a literal interpretation of Genesis, Hitchcock attempted to bridge the gap between geology and theology as the Bridgewater Treatises had in England. In his Ichnology of New England Hitchcock concluded:

And how marvellous the changes which this Valley has undergone in its inhabitants! Nor was it a change without reason. We are apt to speak of these ancient races as monstrous, so unlike existing organisms as to belong to another and quite different system of life. But they were only wise and benevolent adaptations to the changing condition of our globe. One common type runs through all the present and the past systems of life, modified only to meet exigencies, and identifying the same infinitely wise and benevolent Being as the Author of all. And what an interesting evidence of his providential care of the creatures he has made, do these modifications of structure and function present! Did the same unvarying forms of organization meet us in every variety of climate and condition, we might well doubt whether the Author of Nature was also a Providential Father. But his parental care shines forth illustriously in these anomalous forms of sandstone days, and awakens the delightful confidence that in like manner he will consult and provide for the wants of individuals.

If God provided for birds that could neither sow nor reap their own food surely He would have also cared for the enormous avians of old (and even more so the human "lords of creation"). Hitchcock believed that only God could have so perfectly fitted organisms to their surroundings, but this view of nature crumbled as naturalists increasingly tried to understand nature on its own terms and not as a moral lesson. Charles Darwin's 1859 treatise slammed the door shut on the concept of natural theology as science, which Hitchcock subscribed to, but this new perspective on life's history raised new questions.

Birds were so different from other vertebrates that they appeared to be perched on their own lonely branch in the tree of life. How could they have evolved? Hitchcock's tracks hinted that true birds had been present nearly as long as reptiles and amphibians, and the discovery of a fossil feather in 1860 from Solnhofen, Germany, did nothing to change this quandry. Found in the Jurassic-aged limestone of a quarry mined for stone to make lithographic plates, the delicate fossil was acquired by the German paleontologist Christian Erich Hermann von Meyer. In 1861 he named it Archaeopteryx lithographica, the "ancient feather from the lithographic limestone."

Not long after von Meyer described the feather, another nearby limestone quarry produced an enigmatic skeleton. The jumbled creature had a long bony tail but was surrounded by feather impressions; it was as much a reptile as it was a bird. Rather than going straight to a museum, however, the specimen was given to the local physician Karl Häberlein in exchange for medical services.

Rumors of the specimen began to circulate among naturalists, but Häberlein would not part with it easily. He stipulated that the fossil would only be sold along with the rest of his fossil collection, raising the cost beyond the reach of many prospective buyers. Richard Owen and George Robert Waterhouse, certain that Archaeopteryx would bring prestige to the British Museum, were able to convince the trustees of the institution to forward £700 for the fossil (or what the museum would normally have spent on new fossil acquisitions over the course of two years). By November 1862 the fossil was in London.

Some German naturalists were upset that the slab had been expatriated to England, but the august University of Munich professor Johann Andreas Wagner had opposed efforts to acquire Archaeopteryx for his college. He was sure it was not all it seemed. Although Häberlein tried to restrict access to the specimen amid rumors it was a fake, a verbal report and sketch of the fossil reached Wagner, who argued that rather than a bird, it was a kind of reptile he called Griphosaurus, or "riddle reptile."

Wagner's fears over evolution had spurred his impulsive description. Archaeopteryx sounded like just the type of transitional form that would throw support to Darwin and Wallace's evolutionary theories, and Wagner's warnings about the fossils were among the last of his publications before his death.

Owen's description of the fossil was read before the Royal Society in 1863. He appraised it as the "by-fossil-remains-oldest-known feathered Vertebrate." More than that, the fossil was most certainly a bird despite its reptilian characteristics, and Owen upheld von Meyer's original name Archaeopteryx. This diagnosis allowed Owen to make a particular prediction. The head of Archaeopteryx was missing, but Owen reasoned that "by the law of correlation we infer that the mouth was devoid of lips, and was a beak-like instrument fitted for preening the plumage of Archaeopteryx."

While some naturalists felt that Owen's description was rather crude, the news of the fossil was welcome among evolutionists. In an 1863 letter to Darwin the fossil mammal expert Hugh Falconer beamed,

Had the Solenhofen quarries been commissioned — by august command — to turn out a strange being à la Darwin — it could not have executed the behest more handsomely — than in the Archaeopteryx.

This news made Darwin eager to hear more about the "wondrous bird," yet he ultimately did little to present Archaeopteryx as a confirmation of his evolutionary ideas. In the fourth edition of On the Origin of Species published in 1866, Darwin primarily used Archaeopteryx and Hitchcock's tracks — by now thought to have been made by dinosaurs — to illustrate that the fossil record still had secrets to divulge. "Hardly any recent discovery," Darwin wrote of Archaeopteryx, "shows more forcibly than this how little we as yet know of the former inhabitants of the world." Even as it hinted at a connection, Archaeopteryx was too weak to unequivocally bridge the gap between reptiles and birds by itself. The necessary evidence would be supplied by the anatomist Thomas Henry Huxley.

Huxley began his scientific career in 1846 by studying marine invertebrates while serving as an assistant surgeon aboard the HMS Rattlesnake. His work was well received by other naturalists, and when he returned to England in 1850 he was set to establish himself among the scientific elite. Like the man who would become his rival, Richard Owen, Huxley was most concerned with the underpinnings of anatomical form, but where Owen cloaked his work in pious rhetoric, Huxley's distaste for religious interference in science may have attracted him to Darwin's theory of evolution in the first place. While Huxley disagreed with Darwin on some key points, natural selection was the best mechanism yet proposed for evolutionary change. For natural selection to make sense, however, the absence of graded transitions in the fossil record had to be accounted for, which Huxley explained through the concept of "persistent types."

Throughout the fossil record there seemed to be little evolutionary change; crocodiles looked like crocodiles no matter what strata they came from. Instead of being evidence against evolution, however, Huxley proposed that the persistent forms were echoes of evolutionary changes that had occurred in a time so distant that it was not recorded in the rock. If most of evolution happened during "non-geologic time," then the inability of naturalists to explain the origin of major groups of animals with fossil evidence became a moot point. The caprices of geology kept them out of science's reach.