Creationism in Crisis - Evolution by Loss of Genetic Information, or What Made us Human

Creationism in Crisis

Evolution by Loss of Genetic Information, or What Made us Human

Illustration by Michael S. Helfenbein

‘Deletions’ from the human genome may be what made us human | YaleNews

A trio of papers out recently should make creationists feel even more despondent, if only they could find the courage to read them, and if they could understand their contents. I'll write about them over the next couple of days, time willing.

The first, published yesterday in Science, concerns a new study led by researchers at Yale and the Broad Institute of MIT and Harvard, which has shown that, in addition to gaining some new genes that allowed us to speak, for example, what also differentiates us from chimpanzees is about 10,000 lost pieces of DNA, some as small as a few base pairs.

This of course, flies in the face of creationist dogma which says loss of genetic information is always deleterious and so can't contribute to evolution. It's something that creationist guru Michael J. Behe ludicrously calls 'devolution', which is a nonsense term, since there is no mechanism by which deleterious mutations can accumulate in the species gene pool, unless, rarely, they are closely linked to a strongly beneficial mutation.

But then Behe is writing primarily for a readership that doesn't understand what evolution is or the processes that cause it and who have no intention of ever finding out. Instead, they tell themselves that 'evolutionists' believe a mutation can turn a one species into another as a single event. As we've come to expect, creationist dogma is counter-factual because it's based on deliberate misinformation.

These are the same people who have boon fooled into believing that mainstream biologists are turning against the Theory of Evolution and turning to their childish superstition with its magic and an unevidenced supernatural magician. Another creationists delusion refuted by this research paper.

That this is not a case of chimpanzees gaining something that their common ancestor with humans did not have is evidenced by the fact that the genetic information chimpanzees still have is also in the genome of many other mammals. The probability of multiple species all gaining the same small fragments of DNA are incalculably small.

So, what benefits did these deletions convey? That they did so is concluded from the fact that they are present in all humans so must have given a common ancestor and advantage early in. As the Yale News article by Bill Hathaway explains:

What the human genome is lacking compared with the genomes of other primates might have been as crucial to the development of humankind as what has been added during our evolutionary history, according to a new study led by researchers at Yale and the Broad Institute of MIT and Harvard.

The new findings, published April 28 in the journal Science, fill an important gap in what is known about historical changes to the human genome. While a revolution in the capacity to collect data from genomes of different species has allowed scientists to identify additions that are specific to the human genome — such as a gene that was critical for humans to develop the ability to speak — less attention has been paid to what’s missing in the human genome.

For the new study researchers used an even deeper genomic dive into primate DNA to show that the loss of about 10,000 bits of genetic information — most as small as a few base pairs of DNA — over the course of our evolutionary history differentiate humans from chimpanzees, our closest primate relative. Some of those “deleted” pieces of genetic information are closely related to genes involved in neuronal and cognitive functions, including one associated with the formation of cells in the developing brain.

These 10,000 missing pieces of DNA — which are present in the genomes of other mammals — are common to all humans, the Yale team found.

Often we think new biological functions must require new pieces of DNA, but this work shows us that deleting genetic code can result in profound consequences for traits make us unique as a species.

[Such deletions] can tweak the meaning of the instructions of how to make a human slightly, helping explain our bigger brains and complex cognition.

These tools [Massively Parallel Reporter Assays (MPRA)] have the capability to allow us to start to identify the many small molecular building blocks that make us unique as a species.

Assistant professor Steven Reilly
Department of Genetics
Yale School of Medicine, New Haven, CT, USA.

The fact that these genetic deletions became conserved in all humans, the authors say, attests to their evolutionary importance, suggesting that they conferred some biological advantage.

The paper was one of several published in Science from the Zoonomia Project, an international research collaboration that is cataloging the diversity in mammalian genomes by comparing DNA sequences from 240 species of mammals that exist today.

In their study, the Yale team found that some genetic sequences found in the genomes of most other mammal species, from mice to whales, vanished in humans. But rather than disrupt human biology, they say, some of these deletions created new genetic encodings that eliminated elements that would normally turn genes off.

The deletion of this genetic information, Reilly said, had an effect that was the equivalent of removing three characters — “n’t” — from the word “isn’t” to create a new word, “is.”

The researchers used a technology called Massively Parallel Reporter Assays (MPRA), which can simultaneously screen and measure the function of thousands of genetic changes among species.

More detail is given in the abstract to the team's paper in Science:

Structured Abstract

INTRODUCTION
Deciphering the molecular and genetic changes that differentiate humans from our closest primate relatives is critical for understanding our origins. Although earlier studies have prioritized how newly gained genetic sequences or variations have contributed to evolutionary innovation, the role of sequence loss has been less appreciated. Alterations in evolutionary conserved regions that are enriched for biological function could be particularly more likely to have phenotypic effects. We thus sought to identify and characterize sequences that have been conserved across evolution, but are then surprisingly lost in all humans. These human-specific deletions in conserved regions (hCONDELs) may play an important role in uniquely human traits.

RATIONALE
Sequencing advancements have identified millions of genetic changes between chimpanzee and human genomes; however, the functional impacts of the ~1 to 5% difference between our species is largely unknown. hCONDELs are one class of these predominantly noncoding sequence changes. Although large hCONDELs (>1 kb) have been previously identified, the vast majority of all hCONDELs (95.7%) are small (<20 base pairs) and have not yet been functionally assessed. We adapted massively parallel reporter assays (MPRAs) to characterize the effects of thousands of these small hCONDELs and uncovered hundreds with functional effects. By understanding the effects of these hCONDELs, we can gain insight into the mechanistic patterns driving evolution in the human genome.

RESULTS
We identified 10,032 hCONDELs by examining conserved regions across diverse vertebrate genomes and overlapping with confidently annotated, human-specific fixed deletions. We found that these hCONDELs are enriched to delete conserved sequences originating from stem amniotes. Overlap with transcriptional, epigenomic, and phenotypic datasets all implicate neuronal and cognitive functional impacts. We characterized these hCONDELs using MPRA in six different human cell types, including induced pluripotent stem cell–derived neural progenitor cells. We found that 800 hCONDELs displayed species-specific regulatory effect effects. Although many hCONDELs perturb transcription factor–binding sites in active enhancers, we estimate that 30% create or improve binding sites, including activators and repressors.

Some hCONDELs exhibit molecular functions that affect core neurodevelopmental genes. One hCONDEL removes a single base in an active enhancer in the neurogenesis gene HDAC5, and another deletes six bases in an alternative promoter of PPP2CA, a gene that regulates neuronal signaling. We deeply characterized an hCONDEL in a putative regulatory element of LOXL2, a gene that controls neuronal differentiation. Using genome engineering to reintroduce the conserved chimpanzee sequence into human cells, we confirmed that the human deletion alters transcriptional output of LOXL2. Single-cell RNA sequencing of these cells uncovered a cascade of myelination and synaptic function–related transcriptional changes induced by the hCONDEL.

CONCLUSION
Our identification of hundreds of hCONDELs with functional impacts reveals new molecular changes that may have shaped our unique biological lineage. These hCONDELs display predicted functions in a variety of biological systems but are especially enriched for function in neuronal tissue. Many hCONDELs induced gains of regulatory activity, a surprising discovery given that deletions of conserved bases are commonly thought to abrogate function. Our work provides a paradigm for the characterization of nucleotide changes shaping species-specific biology across humans or other animals.

Human-specific deletions that remove nucleotides from regions highly conserved in other animals (hCONDELs).
We assessed 10,032 hCONDELs across diverse, biologically relevant datasets and identified tissue-specific enrichment (top left). The regulatory impact of hCONDELs was characterized by comparing chimp and human sequences in MPRAs (bottom left). The ability of hCONDELs to either improve or perturb activating and repressing gene-regulatory elements was assessed (top right). The deleted chimpanzee sequence was reintroduced back into human cells, causing a cascade of transcriptional differences for an hCONDEL regulating LOXL2 (bottom right).

Abstract
Conserved genomic sequences disrupted in humans may underlie uniquely human phenotypic traits. We identified and characterized 10,032 human-specific conserved deletions (hCONDELs). These short (average 2.56 base pairs) deletions are enriched for human brain functions across genetic, epigenomic, and transcriptomic datasets. Using massively parallel reporter assays in six cell types, we discovered 800 hCONDELs conferring significant differences in regulatory activity, half of which enhance rather than disrupt regulatory function. We highlight several hCONDELs with putative human-specific effects on brain development, including HDAC5, CPEB4, and PPP2CA. Reverting an hCONDEL to the ancestral sequence alters the expression of LOXL2 and developmental genes involved in myelination and synaptic function. Our data provide a rich resource to investigate the evolutionary mechanisms driving new traits in humans and other species.

James R. Xue et al. ,
The functional and evolutionary impacts of human-specific deletions in conserved elements. Science 380,eabn2253(2023). DOI:10.1126/science.abn2253

© 2023 the authors, published by American Association for the Advancement of Science.
Reprinted with kind permission under license #5538271356518.

And this is just the first of three recent papers which utterly refute creationism's central dogmas, as do all serious biology research papers, of course. This one refutes the lie that biologists are abandoning the TOE, the lie that loss of genetic information can't be evolutionary and the lie that all mutations are detrimental and, in some way, 'devolutionary'. This is going to be a difficult few days for any creationists who understand this stuff.

The next article looks at how the human and other mammalian immune systems evolved.

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